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Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

TABLE OF CONTENTS ................................................................................................................................................. 1

BIOCHEMISTERY ................................................................................................................................................ 1
PROTIDS ................................................................................................................................................................ 1
LIPIDS OR FATS .................................................................................................................................................... 49
THE SACHARIDS OR GLUCIDS ............................................................................................................................... 64

BIOCHEMISTRY ADDENDUM .................................................................................................................................. 73

Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

The vast collection of complex substances that is called protids has in common that it is constituted by organic
molecules with a nitrogen component. In this class of substances we find for instance:

Amino acids (building bricks see addendum)
Peptides (cemented bricks: peptide bound as cement)
Polypeptides (peptide chains or walls of bricks, even rooms)
Proteins (a complex conglomerate of polypeptides: a building)
Nucleic acids (building blocks of genetic material )
Nucleotides & nucleosides (n-base bounded with a sugar and a phosphate group )
(the bricks of DNA and RNA .)

Aminoacids are categorized in different ways. We will review a few ways that are important while the permit to see the
form of Aa. (Amino acids) They are perfect examples on the molecular level to learn to see that FORM is structure and
function in one. Later seeing the form is important to see physiologic processes.
Amino acids: (Aa. )
 -Proteïnogenic Aa.
 -Non-proteïnogenic Aa .
(these arise after enzymatic modification or posttranslational modification ) Proteïnogenic amino acids
The group is constitued by 20 different Aa. that are all programmed and encoded in the genetic material of all living
organisms with a specific code. Our proteïns are thus chains of different combinations of these 20 Aa.
The Aa. Glycin is the only exception in its basic structure and thus form, all other 19 Aa. Have the same basic structure
but a different form (electromagnetic).

Amino acid schematic basic structure

(With the exception of Glycin!)
The 19 types Aa. All have the same basic structure namely :
- a central carbon atom that is called the chiral center . (-carbon atom)
- 4 surrounding groups:
- An amine or nitrogen group (alkali) NH 2 or NH 3
- A carboxyl group (acid) COOH or COO
- A hydrogen atom H
- A variable group which is called Rest group or symbolized as R.


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Figure 1: Schematic representation of the Aa. basic structure
Two dimensional

Three dimensional

Out of this basic structure follows automatically a form with logical and typical characteristics.
This is the first molecular level where we are confronted with Form or the inseparable relationship between structure &
In other words, we see the relationship between anatomy and physiology, if we jump to the dimension of the body.

Characteristics of Aa. that are included in the form.

The first characteristics of Aa. that flows out of their structure and thus make their form is stereochemistry and the
enfilading optical activity.
As the Aa. Glycin is an exception in its basic structure it will also be an exception in these typical characteristics!

Stereochemistry: practically this means as much as the mirror image, in other words round the central C atom
or chiral center the 4 groups can take place in a mirror image configuration. Depending on the configuration
the molecule takes, it will form left or right Aa.. The terminology left or Levo-Aa . and right or Dextro-Aa .
is derived of the optical characteristics. (Optical activity) In nature it is so that the L-form is the most
present; all until now known living organisms use the L-Aa. In the eighty’s (1985) American scientists
discovered that “the older a biologic system gets the ofter it starts to use D-Aa., although they are biological
nonsense. As they have another form they have different physico-chemical characteristics than the L-Aa. ; in
other words the older an organism gets the more it uses time energy and matter in building useless
molecules. This nonsense apparently happens increasingly and so systematically that it can be used as a
forensic method to assess the age of death of an organism with a precision of approximately 6 months in


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Figure 2: Schematic representation of stereochemistry
Levo-amino acid

Dextro-amino acid

Optical activity :
Definition: Licht is an electromagnetic phenomenon that can be demonstrated in two configurations: a wave
behavior (lightwaves) and a particle behavior (photons). For the optical activity understanding it is best to
observe the wave behavior.
Light in its free form consists in a sinusoid wave pattern that runs in all directions when you look at it with a
sagital view.
Figure 3 : Schematic representation of light in a wave pattern.
Two dimensional representation

Three dimensional representation


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

We can polarize light, than it is not free anymore but only one type of sinusoidal waves are left over. A polarisator is a
filter that stops all waves but one direction (sunn glasses) Look at the schematic representation.
Figure 4 : Schematic polarization of light.

Light waves
Free form

light filter

polarized light

If now we place a second polarisator after the polarized lightbeam, we can start our experiment. Experiment 1: the two
polarisator’s n°1 and n°2 are placed vertically. Solely vertical orientated light waves pass. When we turn the polarizing
filter n°2 for 90° the filter direction is horizontal. All waves are stopped now, there is no light passing through
Figure 5 : Schematic representation experiment 1 – optic activity



Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Experiment 2: We place a glass container filled with water between polarisator n°1 and polarisator n°2. No change,
behind polarisator n°2 there is still no light passing through.
Experiment 3a: We dissolve D-Aa. in the water container. Once the solution is homogenous, we see a strang
phenomenon, although de two filters were left untouched, light reappears behind the second polarisator.
Conclusion 3a: the D-Aa. Have turned or rotated the lightwaves which allows them to pass through the second
polarizing filter.
Experiment 3b: When we rotate the second filter once more the light beam after the second filter dissapears and
darkness comes in.
Conclusie 3b: the D-Aa. Demonstrate a rotation optical activity, they turn the light waves. L-Aa. Do the same but in he
opposite direction. Optical activity (quantified by the rotation of the plane of polarized light as it passes through a
Figure 6 : Schematic representation of experiment 3 – optic activity

These experiments demonstrated dat stereochemistry and optical activity are two characteristics of Aa. that are related to
their structure and configuration. These two characteristics are linked.
The Levo - and Dextro- denomination of Aa. is clear after these experiments, the polarimeter measures if the molecules
turn the light left (-)or rightwise(+).
Biologic systems function with Levo –Aa. configurations.


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Amfotere characteristics of Aa.

Even this chemical characteristic is related to the structure. The amino acid got his name because it always has one alkali
amino group (NH2 or NH3) on one side and an acid carboxyl group (COOH or COO) on the other side. Thus as always
“form” beholds structure and function or behavior. The Aa. thus contains at least two ionisable groups; the ionic state or
electric charge of the groups and thus the all molecule is dependent on the pH of the environment in which the system
molecule is embedded. At a neutral pH (7-7,6) most Aa. have reached their iso-electric point or status . The iso-electric
point is the condition wherein the electric charges are equally distributed and when the Aa.molecule has a neutral
electric behavior. (Blood has normally a pH of 7.4).
What is an amfotere characteristic than exactly?
To understand this right we have to make a quick turn towards the classic chemistry definition of acids and alkali’s or
Classic chemical definition:
- An acid is a molecule that behaves as a protondonor, in other words a molecule that can deliver a hydrogen-ion.
(H+ donor).
- A base is a molecule that behaves as a protonacceptor , in other words a molecule that can accept a hydrogen-ion.
( H+ acceptor).
Through the fact that an Aa. has as well an acid – as an alkali or base- side ut can demonstrate the behavior of both
alkali and acid. What is an amfotere characteristic than exactly?
An amfotere molecule can behave as an acid or as a base, depending on the reactionpartner or the pH of the environment
in which the molecule is. An Aa. will behave in a slighthly acidic environment as a protonacceptor (base), but in a
slightly alkaline environment as a protondonor (acid).
In other words an Aa. will within the range of its possibilities help to stabilize pH-variations. Aa. are thus very important
in eukaryotic systems or organisms too maintain a stable pH. (Milieu interne) This amfotere characteristic will also be
present in all complexer forms constituted by Aa. such as peptides, polypeptids and proteins. All protids are thus
homeostatic pH regulators of for instance the body tissues & fluids such as blood. Therefore they are often defined as


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Figure 7: schematic representation of an Aa. in acid and base form.
Protonacceptor – base

Protondonor - acid

Protonacceptor – base

Protondonor - acid


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Classification of proteïnogenic aminoacids

Professionally for our practice the difference between essential and non-essential aminoacids are the most
Non-essential aminoacids :
Non-essential aminoacids are, in our western European feeding habits normally, excessively present. We find these
ingredients in almost all parts of our food: for example: in bread, potatoes, mais and cereals, beans, sprouts, nuts, eggs,
fish, dairy products and meat. How much exactly, from each type of Aa. we take up during each meal does not matter
that much because our liver parenchymal cells contain enzymes that can transform one non-essential Aa. into
another, if there are too few of a sort. On the theme “enzymes” we will come back further on in this course, and to
these specific Aa. transforming enzymes (transaminases) evenso.

Essential aminoacids :
These are evenso excessively present in “NORMAL” variated western food. Nevertheless in daily practice we see
problems on this level, usually with vegetarians, vegans or people that believe they are taking especially healthy diets.
(The longer in time they are feeding like this, the bigger the problems become, up until liver-cyrhosis, severe billary
dysfunctions and so-called autoimmune diseases like pancreatitis and/or Hashimoto syndrome.) Essential Aa. have to be
present in the feedingpattern and enough for the bodily needs because they can not be compensated by the normal
liver physiology! Theoretically it is absolutely possible with a vegeterian feeding style to have all essential Aa. in
sufficient quantities, but this implies a study of what and how much is in the food and how it changes by foodprocessing.
Vegetarians that simply suppres meat and eat carrots, salads and tomatoes instead, get themselves in serious health
troubles in relatively short time (between three & five years).
In practice, sadly enough, one sees the mindless vegetarian trend increasing with pubertarian youths as a way of
rebelling against the conservative society… These situations when the body is confronted with chronic essential
aminoacid shortage are catastrophic especially in children and pubertarians. The liver will destroy its own cells as well
as musclecells will be destroyed in order to provide the necessary Aa. in the bloodstream. Exactly these patients
come often in the hands of all kind of alternative therapeutes and healers because it fits their psychological profile and
because their symptoms usually are not easily poured into a clear syndrome by classic medicine. This is why attention
and awareness to this should be your duty!
Proteinogenic aminoacids are subdivided in 7 structural classes, according to the form and polarity of §he restgroup or
rest chain; usually they are represented by a three letter code see (---)
Class I: Alifatic Aa. . These do not carry within their restgroups: Nitrogen, Oxygen or Sulfur and have never a
ringstructure. Their restgroups are obviously apolar and thus water repellent or hydrophobic.
 Glycin (Gly )
 Alanin (Ala )
 Valin (Val ) *EA* (* Essential Aminoacid *)
 Leucin (Leu ) *EA*
 Isoleucin (Ile ) *EA*


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Class II:
Sulfurcontaining Aa. . These bear in their restgroups a sulfur atom. This characteristic makes them
irreplacable for the stabilisation of polypeptide and proteinstructures by building disulfurbridges (SS bridges ). More
about this further on in the protein-structuration chapter. The class II is also apolar, so hydrophobic .
 CysteÏn (Cys )
 Methionin (Met ) *EA*
Class III:

Aromatic Aa. . These Aa. contain in their restgroups a ringstructure. Only Phenylalanin is apolar, all the
others are polar and thus hydrophilic.

 PHenylalanin (PHe ) *EA*
 Tyrosin (Tyr )
 Tryptophan (Trp ) *EA*
 Histidin (His ) (This one has a slight alkali character, at a pH of 7.4, it reacts as a base.)
Class IV:

Neutral Aa. , these contain hydroxygroups or carboxygroups in their restgroups. Generally they do not
demonstrate an ionisable character although two Aa. from this group are polar.

 Serin (Ser )
 Threonin (Thr ) *EA*
 Asparagin (Asn )
 Glutamin (Gln )
Class V:

Acid Aa.; These carry on their restgroups an extra carboxylgroup, which makes them at a
ionised. (The restgroup is thus slightly acid)

pH of 7,4

 Glutaminacid (Glu )
 Asparaginacid (Asp )
Class VI: Alkalic or Basic Aa., These will at a pH of 7,4 ionize strongly on their restgroup and thus behave in a strong
alkali or basic way.
-Lysin (Lys ) *EA*
-Arginin (Arg )
Class VII: Iminoacid . In this particular case the restgroup takes a special form while it will form a ringstructure with
the central carbonatom. This Aa. is slightly basic and will by its bondproperties in protein or polypeptid
construction usually been used as a bent or bowing piece of the chain. If one focuses on the molecular
construction solely it is not a real amino acid, therefore the denomination iminoacid. (By its bending or
turning behavior we will find it back a lot in twisted or spirally orientated structures for instance later in
collagene fibers.)
- Prolin (Pro )


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015 Non proteinogenic amino acids

Non proteinogenic amino acids are the forms of Aa. that arise after enzymatic intervention on proteinogenic Aa. or in
peptides after posttranslational modification. This happens mostly in the endoplasmatic reticulum and or the Golgi
apparatus (see cytology) In the case of mutations these can play a role in so called pathogenic conditions like cancer; for
example the genesis of free radicals for instance nitrosamins .
What can be of importance for practice, as specific antioxidants are going to counter this formation or eliminate them for
example: vitamin C , vitamin E , vitamin A , selenium , bioflavanoïds or oligomer-procyanids (OPC) . Most of these
antioxidants are present in vegetables, fruit and derivatives of them like juice and wine.
This practical part of the biochemistry is more developped in orthomolecular medicine.
Figure 7 bis Schematic representation of THE PROTEÏNOGENIC Aa.classes Peptids and the peptid bound between two amino acids
Peptids are chains that are formed by the the linking through peptidbounds between proteinogenic Aa..
They have gotten their names and classifications by the way they bind, the structural form they adopt and the number of
Aa. they contain.
peptid = two aminoacids that link through a peptidbound. A peptid is the link.
dipeptid = two bounded Aa. by one peptid link
tripeptide = three Aa. bounded by two peptid links
etc. penta-, hexa-, octo- deca- peptids.
Terminology is generally changed when one is talking about a longer chain of Aa. As far as my knowledge reaches there
is no real norm that defines from how many Aa. or peptid bounds one should transfer to the term polypeptids. The
transfer to the term protein from polypeptide is not based on complexity or number of Aa. but on weightbasis because
that is the easiest to measure probably: When a macromolecular polypeptide reaches the molecular weight of 10.000,
they are converted into proteins, terminologically.
To bind two Aa. efficiently into a peptide there are some conditions necessary:
 two free proteïnogenic Aa.
 a ligase enzym to make the reaction happen
 two protective groups, one on the carboxyl- and one on the aminegroup that should stay free.
The enzyme initiates a quick efficient bond between the amine groups of one Aa. with the carboxylgroup of the other
Aa.. This linking or bound always goes together with a release of a molecule of water! To keep the amfotere properties
of the just formed dipeptid there have to be on the outsides a free nitrogen (amine) group and on the other side a free
carboxylgroup. There are thus two protective groups necessary to cover up or protect these groups in order to let them
out the reaction. In other words: the form does change, the complexity rises but the basic amfotere characteristics are
kept and water free’s when the bond is formed!!!
This is of major importance for practice: embryology, physiology and digestion:
On the places where Aa. are linked together to form petids or proteins there is
water coming free in the environment! Proteinsynthesis is thus a
waterproducing process. During protein digestion the contrary happens: when
proteins are digested their complexity is reduced from protein to polypeptides
and finally from peptids to free Aa. This is a process that absorbs
watermolecules, the water molecules are broken down and disappear within the
molecular structure of the Aa. ! Keep this image in mind it is usefull for
digestive and cellular physiology, as well as for understanding the metabolic
fields in embryology. Polypeptids and proteins are often sticky, therefore the
function of their Form is often, glue, in the animal reign.


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Figure 8 Peptidbond between 2 amino acids

When this linking or bounding reaction is done over and over, a long polypeptid chain will arise. As soon as such a long
chain of aminoacids arises it takes a particular configuration. In otherwords as the complexity of the molecule increases,
the form will change. With this is meant specific morphology and eventually emergent characteristics or emergent
behavior arises for this form. We will take a look at the different forms of configuration immediately but the
physiological roles of peptides and polypeptides are as varied as their structure for instance: transmitters, hormones,
enzymes, transportmolecules, poison, reservemoleculen. Polypeptids and their configuration or morphology
Once that the Aa. get linked and start a peptid-chain, there is not only a change or interaction within the increasing
complexity of the system (the polypeptid itself) but also with the environment (that changes its status too: aminoacids
are taken out of the environment and water is generated in it) and it is the combination of both that makes the
configuration form. During the proteinsynthesis this is called the secondary structure. (See further)
The forms that are taken by these polypeptide-chains in these different configurations is called the principle of selforganization. The principle of self organizing systems is found back through all dimensions of life and in all level-layers
of complexity. Let us take a small theoretical side-step into the world of Complexity, self-organizing systems and
dimensional jumps; before coming back to the practical demonstration of biochemistry and peptides.
Side-step addendum: Complexity and Self Organizing Systems
“If anyone wishes to search out the truth of all things in earnest,
he ought not to select one special science,
for all sciences are conjoined and interdependent.”
René Descartes: “Rules for the direction of the Mind” 1629


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Physics Nobel Laureate: Phil Anderson defined complexity in 1972 as:
Complexity = More
and More is different
More than 1 simple agent may selforganize in collective objects (n x 1) which demonstrate emergent behavior that is
different from the behavior of the simple agent.
This is called emergent behavior or emergent characteristics.
system - a group of interacting parts functioning as a whole and distinguishable from its surroundings (environment) by
recognizable boundaries.
system property - the resultant system no longer solely exhibits the collective properties of the parts themselves (“the
whole is more than the sum of its parts”)
organization - the arrangement of selected parts so as to promote a specific function (emergence)

external organization - system organization imposed by external factors

self organization - evolution of a system into an organized form in the absence of external
constraints. (The system can be its own constraint)
The interaction of the environment and the system is continuous.
Properties of self organizing:
 absence of centralized control (competition)
 multiple equillibria (possible attractors – basic algorithms)
 global order (emergence from local interactions)
 redundancy (relatively insensitive to damage)
 self-maintenance (repair or maintenance mechanisms)
 complexity (multiple parameters)
 hierarchies (multiple self-organized levels with inherent chronology)
Properties of complex systems:
• Agent-based: The basic building blocks are the characteristics and activities of the individual agents in the
environment under study.
• Heterogeneous: These agents differ in important characteristics.
• Dynamic: These characteristics that change over time, as the agents adapt to their environment, learn from their
experiences, or experience natural selection in the regeneration process. The
dynamics that describe how the system changes over time are usually nonlinear, sometimes even chaotic. The
system is rarely in any long run equilibrium.
• Feedback: These changes are often the result of feedback that the agents receive as a result of their activities.
• Organization: Agents are organized into groups or hierarchies. These organizations are often rather structured,
and these structures influence how the underlying system evolves over time.
• Emergence: The overlying concerns in these models are the macro-level behaviors that emerge from the
assumptions about the actions and interactions of the individual agents.
• Relationships are short-range: Typically, the relationships between elements in a complex system are shortrange, that is information is normally received from near neighbors. The richness of the connections means that
communications will pass across the system but will probably be modified on the way.
• Open: Complex systems are open systems - that is, energy and information are constantly being imported and
exported across system boundaries. Because of this, complex systems are usually far from equilibrium: even
though there is constant change there is also the appearance of stability.
• Possessing a History: The history of a complex system is important and cannot be ignored. Even a small change
in circumstances can lead to large deviations in the future. This has been referred to as the "Butterfly effect." 1
1 The butterfly effect is a phrase that encapsulates the more technical notion of sensitive dependence on initial
conditions in chaos theory. Small variations of the initial condition of a nonlinear dynamical system may produce

Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Nested: Another key aspect of complex adaptive systems is that the components of the system - usually referred to
as agents - are themselves complex adaptive systems. For example, an economy is made up of organizations, which
are made up of people, who are systems of organs controlled by their nervous systems and endocrine systems,
which are made up of cells - all of which, at each level in the hierarchy, are complex adaptive systems.

Polypeptids and their configuration or morphology continued
The form taken by the polypeptid chain in a specific configuration is automatic or spontaneaous by the self organizing
properties and the fact that certain agents (Aa.) are linked in a specific order. In a polypeptidchain the different Aa. are
going to stabilize the chain by organizing extra links inbetween each other such as: Hydrogen bridges H-H and
Disulfurbridges S-S)
Other inherent forces to the complexity of the molecule and forces of the environment will play a role in the Form or
configuration of the polypeptidchain as we will see in the tertiary structuration of proteins.( See chapter

large variations in the long term behavior of the system. So this is sometimes presented as esoteric behavior, but can be
exhibited by very simple systems: for example, a ball placed at the crest of a hill might roll into any of several valleys
depending on slight differences in initial position.
The phrase refers to the idea that a butterfly's wings might create tiny changes in the atmosphere that ultimately cause
a tornado to appear (or prevent a tornado from appearing). The flapping wing represents a small change in the initial
condition of the system, which causes a chain of events leading to large-scale phenomena. Had the butterfly not flapped
its wings, the trajectory of the system might have been vastly different.
Recurrence, the approximate return of a system towards its initial conditions, together with sensitive dependence on
initial conditions are the two main ingredients for chaotic motion. They have the practical consequence of making
complex systems, such as the weather, difficult to predict past a certain time range (approximately a week in the case
of weather).


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015 Bond-forces that organize the configuration of the polypeptidchain

Hydrogenbridges (HH) : as mentioned above, some of the Aa. that form the chain are going to use common H+
ions and thus form HH bridges or bounds. These HH bridges are strong enough to induce a part of the
configuration but from a physico-chemical point of view they are not strong bounds.
Disulfurbridges (SS) : These are bridges that arise between Sulfur containing Aa., whereby the S atoms of several
Aa. are going to share one or more electrons. In contradiction to the HH bridges, the SS bridges are strong and
resilient. This can easily been seen for instance in the application of muccolytica (N-acetylcysteïn) that break and
hinder the formation of these bridges.(* see addendum)

Electrostatic interaction : certain groups attract each other while other repulse one another, there is no material bond but
the formative action is as important: the forces will rotate, twist, approach or distance some of the groups accordingly
changing the morphological aspect of the whole! The configuration-forms of the polypeptidchain.
Actually, just three big configurationforms can be distuingished, which each can be subdivided in two.
 The  Helix configuration
 The  Pleated sheet configuration
 The C Bend configuration
Each of these configurations come in two types namely:

The  Helix configuration

In this configurationform the polypeptid chain is twisted spiraly around an imaginary axis like a propellor or Archimeds
 The dextro  Helix :
The right turning  helix is the most common type that is found back in nature, although it would be no problem to
form a left turning Helix it is rare in a natural form.
Due to the Form and twisting angle of each of the Aa. around the imaginairy axis of the  Helix there is a multiple
formation of HH bridges between the Aa.. The presence of these HH bridges stabilzises the  Helixconfiguration.
The HH bridges lay like little pontoons between the NH and CO groups of the Aa. while the restgroups are usually
orientated towards the outside of the  Helix .
 The levo  Helix :
The left turning  Helix is in its natural form not so common as its symmetrical right turning partner, although
there is one very important exception namely the collagene helix structure. Collagene is not really the symmetrical
image of the right form because the twisting or bending degree is much higher. This form does not permit HH
bondages in between the Aa. of the same chain. As we will see later in detail: the collagene is build up by a triple
helix twisted in each other (like old hennep ropes in the gymnastic hall), and they will form many HH bridges
between each chain thus solidifying the all.


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Figure 9 The dextro  Helix

Figure 10 The levo  Helix (collagene helix)

Figure 11 The tripple helix of the collagene fibre.


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

The  Pleated sheet configuration

In this type of configuration the polypeptid chains lay next to another, parallel like the tracks of a railroad. The HH
bridges arise between the Aa. that lay next to each other.
The -C atoms are always on the highest or lowest point of the rails makes the Restgroups to tend to up or downwards,
this makes a particular form that one could compare to a pleated sheet or the outside of an accordeon.
The facts that an accordeon is not an international instrument and furthermore that an accordeon is made out of two
pleated sheets made that the name Pleated sheet were witheld. There are two kinds of  Pleated sheet configurations: a
parallel one and the antiparallel one which brought these two code shortnames:  a for  antiparallel Pleated sheet
configuration and  p for  parallel Pleated sheet configuration .
- Antiparallel Pleeted sheet: ( a)
In this polypeptide chain configuration, the two parts of the chain were the HH bridges occur are orientated in a
antiparallel way. (See Figure12)
-  Parallel Pleeted sheet: ( p)
In this polypeptide chain configuration, the two parts of the chain were the HH bridges occur are orientated in a
parallel way. (see Figure 13)

Figure 12 The  antiparallel pleeted SHEET CONFIGURATION (a)


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Figure 13 The  parallel Pleeted sheet configuration ( p)

The C Bend configuration

This configuration always consits of a tetrapeptid that is bend in a bow of 180° , and always with a HH bridge between
the first and the fourth Aa. that stabilizes the bow form.
The structural effect of this configuration in a more complex polypeptid or protein is that it reorients the next peptid
chain that is attached with a turn of 180° in a new direction. The name C Bend recollects the structural function or
effect of this tetrapeptid more than on its own form.
There are two types of C Bend configurations, by both the HH bridges are between the same Aa. (1-4), with both the
bend is 180°; the only difference between the two types is the position of the acid carboxyl group COOH on the third
Aa.3 and the position of de alkali NH group of the second Aa. 2. (See Figure 14 and 15)
Figure 14 The C Bend configuration type 1


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Figure 15 The C Bend configuration type 2 Proteïns and their quaternary structuration complexity Definition of proteïns
Proteïns are macromolecules; big molecules with a molmass above 10.000. They are complex constructs of
polypeptidchains, which are themselves complex constructs of aminoacids; and as seen in the beginning Aa. are
themselves already structural complex biomolecules. These complexities within complexities give them very specific
Forms and thus specific structures that go together with very specific behavior or characteristics (functions). Primary structure of proteïns
The primary structure of proteins lies thus in the exact chronology or order in which the different Aa. follow each other
up in the chain. The plan of chronology followed is the RNA that is a copy of the DNA. The executant of the plan is the
raw endoplasmatic reticulum.
The exact chronology of the Aa. is the first step in the complexity of proteinstructuration that leads to a a specific Form
(structure and behavior)

Alike a Fractal image constructing: one small error in the fractal will be reproduced and increase thus leading to a
completely different form: see butterfly effect.


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

If we use the image that a protein is constructed like a complex building with mosaic patterns on the walls, than we can
say that the primary structure of the protein is the chronology of the stones of different colors that are used to build the
A practical example: Sickle cell anemia
Sickle-cell anemia is a genetic induced deffect of red blood cells that was originally
found in the Negroid population of the USA and central Africa. Sickle-cell anaemia
is caused by a point mutation in the β-globin chain of haemoglobin, replacing the
amino acid glutamic acid with the less polar amino acid valine at the sixth position
of the β chain. The consequence is that the red blood cells become sickle shaped
instead of wheel like form. These type of sickle cells can transport less than half of
the Oxygen in comparison with a normal blood cell; furthermore as their form
makes them less elastic they tend to obstruct capillaries. Evolutionary Osteopathy
teaches us that if a mutation is transmitted and kept in the gene pool it must have a
Evolution of a defective gene
Researchers believe the defective hemoglobin gene that causes sickle cell anemia evolved many years ago (75.000150.000 years ago), among people living in parts of Africa, the Mediterranean, the Middle East and India. At that time,
malaria epidemics killed many people in those regions. But some people in those regions had a genetic mutation that
caused some of their red blood cells to change shape — a condition now known as sickle cell trait. The sickle cells
actually interfered with the growth of the parasite that causes malaria. So people with sickle cell trait often survived
malaria outbreaks. Over time, these survivors migrated and continued on with their lives. In some cases, two people with
the sickle cell trait had children. And some of their children inherited two copies of the mutated gene, which results in
sickle cell anemia. Today, millions of people all over the world have sickle cell anemia.

In green the Malaria distribution.

In pink the Sickle cell distribution.


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

The secundary structure of proteins

The secundary structuration of proteins was all ready described above. The forms in the secondary step are the forms of
polypeptidchains, with their HH and SS stabilizing bridges.
- Helix rightturning
- Helix leftturning (collagene  Helix)
- Pleated sheet paralell
- Pleated sheet antiparalell
-C Bend configuration type I
-C Bend configuration type II
If we persevere in our building example the
secundary structure of proteins would be walls,
types of walls with or without windows, doors etc.,
but always with a beautiful undisrupted mosaic

The tertiary structure of proteïns

The tertiairy structure of proteins is the next step in complexity, if we turn immediately to our building example this will
be clear:
We started with aligning bricks (Aa.) in rows forming as we continued a serie of mosaic walls (polypeptidchains
secundary structure), and now we start joining the walls into rooms of different size and morphology ( no or many
windows, one or several doors etc.) these rooms represent the tertiairy structure.

In other words the tertiairy structure of proteins consists in linking different polypeptidchains together and thus creating
a much larger, more complex three dimensional structure with a very specific Form (structure and behavior or
properties). The combination of  helixes with other  helixes or  pleeted sheats and  bendconfigurations to change
directions (corners of the rooms) make the structure, whereas HH and SS bridges consolidate the whole.


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015 Configurating elements, internal junctions and chaperononins

The elements (forces and substances) that we will discuss now are not only for the tertiary but even so for the
quaternary structuration of the proteins. At these levels of structuration of complexity, we see that the molecular mass or
weight and volume will dramatically increase, in the same moment the structural complexity or spatial specificity
increases automatically. This complex Form, includes structure and function or behavior! If anything changes or alters
this Form it will not only change the structural aspect but its behavior as well: in physiology this is called denaturation.
Usually in complex proteins denaturation is irreversible, and the organism will destroy, decomplexify these proteins and
recycle them or eliminate them. (For instance making a scrambled egg is a typical proteinic denaturation process; and
the best laboratory in the world can not reverse this process once it happened.
Lets return to our classic example, the elements that we will see now are the beams, angle-reinforcements, pillars and
others that give that special look to the building. Whereas the chaperonins, specifically are as well the decorative
architects as the structural ingeneers that create an elegant atmosphere and a solid construction that is unique and
recognizable at first glance.
The configuration elements and internal junctions are:

HH bridges
SS bridges
Electrostatic interaction
Hydrophilic and hydrophobic forces
Van der Waals forces (cohesion forces )

HH hydrogen bridges : as mentioned above, some of the Aa. that form the chain are going to use common H+ ions
and thus form HH bridges or bounds. These HH bridges are strong enough to induce a part of the configuration but
from a physico-chemical point of view they are not strong bounds.

Disulfurbridges (SS) : These are bridges that arise between Sulfur containing Aa., whereby the S atoms of several
Aa. are going to share one or more electrons. In contradiction to the HH bridges, the SS bridges are strong and
resilient. This can easily been seen for instance in the application of muccolytica (N-acetylcysteïn) that break and
hinder the formation of these bridges.(* see addendum)

Electrostatic interaction : certain groups attract each other while other repulse one another, there is no material
bond but the formative action is as important: the forces will rotate, twist, approach or distance some of the groups
accordingly changing the morphological aspect of the whole! (Magnetic force)

Hydrophylic and hydrophobic forces (behavior) : Physiologically proteins are in use in a watery environment, some
parts of the proteins are hydrophylic while other parts are hydrophobic. The fact that they are build in a water rich
environment will twist and turn the parts dependant on if they like or dislike the polar behavior of water. The
hydrophylic parts will tend to turn on the outerside of the protein molecule, whereas the hydrophobic parts will
tend to turn as much inwards, away from the water as possible. This shuffles the structure, Form and behavior once
more. (In the cas of lipoproteins for instance, the hydrophobic parts will orientate towards the lipid side while the
hydrophilic parts will turn towards the outside: blood and waterside.

Van der Waals forces (cohesion forces ): The Dutchman Van der Waal discovered that proteins as enormous
molecules with huge molecular masses develop certain cohesion forces. The more masse a molecule has the bigger
the Van der Waals forces are. Mathematically this is absolutely correct but from a physiological point of view
these forces are so minimalistic that they can be considered as negligible.

Chaperonins : are small peptidchains that play a leading role in the folding process of the proteins. Apparently
they are responsible for the correct folding that make proteins in the right Form that makes them physiologically


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

usable. (As this is true for all eukaryotic organisms, the chaperonins play this role since the beginning of eucaryotic
cells, at least 1.2 billion years). That Chaperonins are the engineers of complex proteins in living organisms is
easily demonstrated because they become necessary as soon as the protein contains more than 300 Aa., below this
critical mass, the folding can happen right without the help of chaperonins. In other words synthetic proteins are
“easily” synthetically made up to 300 Aa., once the molecule is bigger we need to pass by a living organism to use
its chaperonins (bacteria for instance can produce human insulin after that part of the human genome is inserted in
their DNA. Genetically manipulated Escherischia Coli is used for that prupose by the pharmaceutical industry.)
The synthetical version without the help of a living organism can be made, with the same order of Aa., but because
it will not be folded correctly it will have another Form and thus another behavior: inusable in livuing organism.
In our example of the building the chaperonins are the master engineer and architect who’s touch is inimitable: if
he was not present in the process of building you can approximate the result but the difference is visible and
expresse in a non functionality.

A construction example of
a bad tryout

The quaternary structuration of proteins

The difference between the 3d and 4th structuration complexity of proteins is relatively small, the quaternary
structuration comes in play in huge proteinmolecules with enormous molecular masses. (such as enzymes for instance)
Thus big complex proteins can be seen as overgrown tertiary structures wherein some sequences are repeated.

Our building example for clarity, so that you do not lose the picture: in a big building on the different floors there
rooms and walls that are exactly the same as on other floors, or the sequence is repeated several times in the building.
Do you see the picture? Reduce it on polecular dimension and keep it in mind.
Synthesis of our building example and protein structuration:


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

The 20 colored bricks of different sizes are the 20 different Aa.

The cement is our peptid junction that like cement gets solid when it exudes its water

The rows of bricks in line are the peptidconfigurations

The different types of walls that arise when we contue the construction are the polypeptids with their
configurations (  helix etc.) (secundary structure)

By assembling different walls we get rooms (tertiary structure )

By assembling different rooms we get a house or building with some rooms that are alike (repeating sequences).
(quaternary structure ) In a big building even some entire floors will be exact copies or repetition of sequences.

In our example of the building the chaperonins are the master engineers and architects who’s touch is inimitable,
they give the definitive look and flair to the building: if they were absent in the process of building you can try to
approximate the result but the difference is visible and expresses non functionality. Keep this picture in mind
because later when we look at the digestion process we have to do the same mental excersise again in the opposite
direction= decomplexifying our building to bricks again or our protein to Aa.


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

According to the Van der Waals model (cohesion forces ) one could suspect that: the more massive and the more
complex a protein is, the stronger and more stabile it should be. Nontheless is true. The Van der Waals forces are almost
negligible, actually the only real strong stabilisators are the SS bridges.
The SS bridges are covalent2 bonds and thus chemically and physically relatively stable and strong bonds. All other
configurating forces are only stable in a relatively narrow spectrum of environmental conditions: Pressure, pH,
temperature, Osmolarity etc… As soon as a stimulus or input is bigger than the spectrum of this typical protein it will
denaturate. For example bacteria that florisch and reproduce at incredible rates in our body at 37°C are going bad and
even die because of their protein denaturation at temperatures above 39- 40 °C. This is one of the defensive actions of
In other words many factors that we call “Homeostasy” and physiologic conditions are not much more than keeping a
stable and eventually optimal local environment for our proteins, so that they are at the best capacity to demonstrate
their natural behavior ( a pure physiologist would say: too fulfill their function) I do not agree completely with this view
because there is no purpose in evolution, it just happens when the conditions are right, and this is not different for our
human physiology, our physiology developed through billion years of evolution, complexity increasing and systems and
environment interacting on each other, the whole evolving on.
When optimal homeostasy is not the case for whatever reason, we do not feel optimal or even sick, when the proteins
start to denaturate in high tempo, we feel deadly sick and eventually we will die.
One could almost say that the whole of our so called complex physiology is actually nothing else than a machinery that
has as first and main aim to keep the right environment for our specific proteins. (One of the first steps in the hierarchy
of life) Crazy…? Try not to get to stiff in your minds, for example: who can state with certainty that, for example,
chickens are just merely the egg its only possible way to reproduce itself and that actually it is the egg the first subject
and not the chicken? The reference norms of our brain (conscious or not) make us look from one perspective and thus
direct our perception.
This is a very fundamental question of perception and a lot of idea’s, expressions and measurements in physiology and
medicine are nothing more than such solitary, tunnelview type of perceptions, which does not mean at all that they are
the one and only truth. No, it is one way of observing and giving a meaning to something that just is3; physiology is easy
for as far that what you need for your Osteopathic practice, but than and only than when you can look at the Form, the
systems and the Mechanism that makes it run: Complexity in multiple dimensions or more correctly the functioning
of Complex adaptative systems or Self-organizing systems.
Enough philosophy, let us return to protein denaturation for now: As soon as there is a little too much stress (physical or
chemical) on the protein that makes bonds disrupt, the protein starts to denaturate. This denaturation can be in the whole
of the protein or just in one section, but wherever it is, denaturation changes the spatial or structural three dimensional
order and thus changes its Form partly or completely. (As said so before Form = morphology or structure and
behavior or function) The consequence is as the Form & behavior changes the protein is not able to fulfill its so-called
physiological function anymore and will be recycled in the organism.
Often it is so that the complexer a protein is in its configuration, the lesser stability it has, or the more susceptible it gets
for denaturation. This makes often that theyr are constantly broken down, recycled and build up again. When the health
and environment of any living organism is perfect, it will have dynamic equilibrium between the genesis and recycling
and denaturation of proteins among others.
When you understood fully how the complexity of a protein is formed, you know that a denaturated protein is
irreversibly deformed and thus not functional for an organism physiology anymore.
Practical example: children above 24 months of age and pubertarians have high prodution rates of proteins than adults
and older people. Thus high fever (40-41°C) is not directly a catastrophy because their vital proteins will denaturate but
if this situation (environmental stress on the proteins) does not last too long they will recover rapidly because of the

Covalent bonding is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. In short,
attraction-to-repulsion stability that forms between atoms when they share electrons is known as covalent bonding.
Reality is. What we make of its multidimensional, incommensurable ungraspable greatness and complexity is a short synthetic
version that suits us: our perception, our worldviews, our norms etc. Objectivity in observation is per definition insanity, because it
can only exist in a very restrained dimension and restrained environment with as few parameters as possibly controllable. (and that is
per definition contrary to reality that is an open system interacting constantly with its environment.) This goes that far that when you
extrapolate the results of a perfectly scientically controlled experiment; it is not scientific anymore because the parameters change if
you apply it in the outside world, far from its controlled parameters, which does not mean that it can work or at least partially. The
way we interpret its result is personal perception again.


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

production ratio. In adults this becomes more critical because they do not have the same recovery rates anymore. (of
course the bodymasse also plays a role, and then how the fever is managed through physical means)
What are the most important stress factors for proteins in mammal organisms:
 temperature (to high)
 acidification degree variations (pH)
 reducting substances (chemical reductors ) reffined sugars for instance.
 osmolarity (concentration of the environment) (salt-water household )
 high energetic radiation (X-rays, cosmic radiation)
 etc.

RELATION TO EVOLUTION. Evolution line and proteïns
The further an organism stands in the lineage of evolution, thus the higher its complexity, the more proteins it will
involve in its physiology and structure (Form) (see addendum biochemistry***)
Let us take a look at some examples:


Prions hit the media, worldwide in 1995-1996 in relation to B.S.E ., Scrappie , or Englisch Mad cow disease . In humans
Jacob Creutzfeld syndrome = destruction of the cerebellum, and later the whole brain.
What are prions?
The word “prion” is derived from “proteinaceous infectious particle” which refers to the initially heretical hypothesis
that the infectious agent causing, the now worldwide well-known B.S.E. and human variant Kreuzfeld-Jacob, would be
only a protein with no nucleic acid genome. This was coined by Stanley B. Prusiner of the University of California
School of medicine at San Fransisco in 1982.
The prion was discovered to be a primarily normal protein bound to cell membranes, however somehow it got distorted
and thus changed its conformation (configuration or Form) or got an altered shape.
The hypothesis now is that the distorted protein could bind to other proteins of the same type and induce them to change
their conformation as well. In doing so it would produce a chain reaction that would exponentially increase by
generating new infectious material, and thus propagate the disease up to symptomatic range. Prions can be transmitted,
possibly by eating and certainly by inoculation either directly into the brain or into the skin and musculo-fascial tissue.
(Cornea grafts, tendon or skin grafts)
The prion theory has not been proven correct, but a good deal of evidence now strongly supports it.
It is still not known why the distorted membrane protein would result in neuron-degeneration, but it is known that the
prion protein accumulates in brain tissue. One part of the protein can induce apoptosis or programmed cell death.
Conclusion: prions do not really replicate themselves, but induce transformation of shape or distortion in similar
proteins already present.
Thus C. de Duve’s proposition is right, and prions are probably a natural defect but they only arose relatively late in


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Synthesis: prions are proteins


A higher step into complexity are the virusses but here the debate stays open, can we call virusses “Living organisms”?
They are complex parasitical systems that only demonstrate activity when they have entered a hostcell. The structure of
viruses is usually: a piece of nucleic acids, DNA or RNA (see further) encapsulated in a protein container. Often the
protein container or mantle of the virus ends up in a hollow microtube structure (like an injection needle) with round it
contractile proteins like the clasps of a moonlander. A nice demonstration of how in proteins, Form demonstrates
structure and behavior or function: clasps with a cellular docking function, contractile proteins that react on the docking
on, and a protective isolating mantle or container for the genetic information.


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

How are virusses parasites? They need a hostcell to replicate and then need to kill the hostcell to propagate in the
environment. This is the only way their form allows them to behave, as they have no internal replication system.
As soon as their clasps dock on on the cellular membrane of the host, their Form and environment has changed. This
change in form provokes a disbalance in the proteins of the clasps and the injection needle and induces them to contract.
This fast contraction- reaction, induced by the changed form, induces an injection of the viral genetic material in the
hostcell. In the hostcell the viral genetic material will introduce in the genetic material reproduction and proteinsyhtesis,
using the hostcells machinery. This continues until all material is used up and the hostecell bursts while it contains
thousands of new viruses. These new viruses are thus propagated in the environment where the action reaction principle
goes forth.
Synthesis: Viruses are built by several proteins with different forms and some genetic material.
Read this virus review from wikipedia again when you have studied biochemistry and cytology. has an excellent review of the classification of viruses that we took over here below:
Virus classification involves naming and placing viruses into a taxonomic system. Like the relatively consistent
classification systems seen for cellular organisms, virus classification is the subject of ongoing debate and proposals.
This is largely due to the pseudo-living nature of viruses, which are not yet definitively living or non-living. As such,
they do not fit neatly into the established biological classification system in place for cellular organisms, such as plants
and animals, for several reasons.
Virus classification is based mainly on phenotypic characteristics, including morphology, nucleic acid type, mode of
replication, host organisms, and the type of disease they cause. A combination of two main schemes is currently in
widespread use for the classification of viruses. David Baltimore, a Nobel Prize-winning biologist, devised the
Baltimore classification system, which places viruses into one of seven groups. These groups are designated by Roman
numerals and separate viruses based on their mode of replication, and genome type. Accompanying this broad method of
classification are specific naming conventions and further classification guidelines set out by the
International Committee on Taxonomy of Viruses. (Informative)
Classification systems
Baltimore classification
Baltimore classification is a classification system which places viruses into one of seven groups depending on a
combination of their nucleic acid (DNA or RNA), strandedness (single-stranded or double-stranded), and method of
replication. Other classifications are determined by the disease caused by the virus or its morphology, neither of which
are satisfactory due to different viruses either causing the same disease or looking very similar. In addition, viral
structures are often difficult to determine under the microscope. Classifying viruses according to their genome means
that those in a given category will all behave in a similar fashion, offering some indication of how to proceed with
further research.
Viruses can be placed in one of the seven following groups:
Group I: double-stranded DNA viruses
Group II: single-stranded DNA viruses
Group III: double-stranded RNA viruses
Group IV: positive-sense single-stranded RNA viruses
Group V: negative-sense single-stranded RNA viruses
Group VI: reverse transcribing Diploid single-stranded RNA viruses
Group VII: reverse transcribing Circular double-stranded DNA viruses
ICTV classification
The International Committee on Taxonomy of Viruses devised and implemented several rules on the naming and
classification of viruses early in the 1990's. To this day they oversee the naming and placement of viral species into the
framework. The system shares many features with the classification system of cellular organisms, such as taxon
structure. Viral classification starts at the level of order and follows as thus, with the taxon suffixes given in italics:
Order (-virales) Family (-viridae)
Subfamily (-virinae) Genus (-virus)
Species (-virus)

Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

However, this system of nomenclature differs from other taxonomic codes on several points. A minor point is that names
of orders and families are italicized, as in the ICBN. Most notably, species names generally take the form of [Disease]
Virus. The recognition of orders is very recent and has been deliberately slow; to date, only three have been named, and
most families remain unplaced. Approximately 80 families and 4000 species of virus are known.
Virus classification
DNA viruses
Group I: viruses possess double-stranded DNA and include such virus families as Herpesviridae (examples like HSV1
(oral herpes), HSV2 (genital herpes), VZV (chickenpox), EBV (Epstein-Barr virus), CMV (Cytomegalovirus)),
Poxviridae (smallpox) and many tailed bacteriophages. The mimivirus was also placed into this group.
Group II: viruses possess single-stranded DNA and include such virus families as Parvoviridae and the important
bacteriophage M13.
Virus Family

Virus Genus


B 19 virus
Herpes Simplex Virus, Varicella zoster virus,
Cytomegalovirus, Epstein Barr virus
Small pox virus, Vaccinia virus
Hepatitis B virus


Virion- naked/ enveloped


Type of nucleic acid

Complex coats


ds circular


RNA viruses
Group III: viruses possess double-stranded RNA genomes, e.g. rotavirus. These genomes are always segmented.
Group IV: viruses possess positive-sense single-stranded RNA genomes. Many well known viruses are found in this
group, including the picornaviruses (which is a family of viruses that includes well-known viruses like Hepatitis A virus,
enteroviruses, rhinoviruses, poliovirus, and foot-and-mouth virus), SARS virus, hepatitis C virus, yellow fever virus, and
rubella virus.
Group V: viruses possess negative-sense single-stranded RNA genomes. The deadly Ebola and Marburg viruses are
well known members of this group, along with influenza virus, measles, mumps and rabies.
Virus Family

Virus Genus

Virion- naked/


Type of
nucleic acid


Reovirus, Rotavirus





Poliovirus, Rhinovirus, Hepatitis
A virus




Norwalk virus, Hepatitis E virus





Rubella virus










HIV-1, HIV-2, Human T cell




Dengue virus, Hepatitis C virus,
Yellow fever virus




Influenza virus






Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015


Measles virus, Mumps virus,
Respiratory syncytial virus




California encephalitis





Rabies virus





Ebola virus, Marburg virus





Corona virus





Astro virus





Borna disease virus





Reverse transcribing viruses
Group VI: viruses possess single-stranded RNA genomes and replicate using reverse transcriptase. The retroviruses are
included in this group, of which HIV is a member.
Group VII: viruses possess double-stranded DNA genomes and replicate using reverse transcriptase. The hepatitis B
virus can be found in this group.
Subviral agents
The following agents are smaller than viruses but have some of their properties.
Family Pospiviroidae
Genus Pospiviroid; type species: Potato spindle tuber viroid
Genus Hostuviroid; type species: Hop stunt viroid
Genus Cocadviroid; type species: Coconut cadang-cadang viroid
Genus Apscaviroid; type species: Apple scar skin viroid
Genus Coleviroid; type species: Coleus blumei viroid 1
Family Avsunviroidae
Genus Avsunviroid; type species: Avocado sunblotch viroid
Genus Pelamoviroid; type species: Peach latent mosaic viroid
Satellite viruses
Single-stranded RNA satellite viruses
Subgroup 1: Chronic bee-paralysis satellite virus
Subgroup 2: Tobacco necrosis satellite virus
Satellite nucleic acids
Single-stranded satellite DNAs
Double-stranded satellite RNAs
Single-stranded satellite RNAs
Subgroup 1: Large satellite RNAs
Subgroup 2: Small linear satellite RNAs
Subgroup 3: Circular satellite RNAs


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Bacteria or unicellulars

The first cell arose as a new level of complexity around 3,8 billion years ago. If we take a look at one of its close cousins
like the Escherischia Coli bacteria (see picture) , than we see that this small organism uses and produces more than 2000
different proteinic enzymes.
Synthesis: Unicellular organisms contain and build thousands of diferent forms of proteintypes .
Virus injecting in an E. coli bacteria



Highly complex organisms like mammals produce many thousands of proteins and polypeptids.
Synthese: Mammals contain sevral thousands of proteintypes .


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015 Functions of proteïns in physiology and Form

Proteïns as structures and structurating molecules

Structuration is the first “role” or behavior that we saw in proteins: in prions and viruses. In mammals the most
important protein that gives us a shape and strength is the collagene protein. In humans it makes up for: 30 % of the
body dry weight. (See later Histology-Connective tissue) Collagene is formed by three intertwined polypeptid chains,
which gives the Form of this proteinic polypeptid and enormous resistance to pull forces. Collagene is the basic
construction pillar of the whole of our support and force-transmission systems (skeleton, joints, tendons, ligaments,
fascia’s etc.)
Some other magnificent examples of the structuring lead-role, proteins play: M.A.P’s. and histones.

Microtubule Associated Proteïns (MAP ): the MAP’s structure the nerve cells through their intervention on the
cytoskeleton. (See further cytology MAP2 example.)
Histones : are proteins present in the cell nucleus where they induce the rolling of nucleic acids (DNA) into
chromosomes .

Proteïns as mobilizing structures

In the chapter about viruses we already saw that some proteins can have by their special form contractile characteristics.
Later in cytology we will see aniother typical contractile protein the actin molecule, this contractile protein is actually
the most basic form of muscle form we find back in mammals. Our striated musculature is only a further
complexification and replication of the actin form. (See histology- muscular tissue)

Proteïns as chemical active substances, catalysators and messengers

On the complexity level of cells, we can observe that proteins are an integral part of the structure of the cellmembrane,
not to speak about the membrane bound proteins. They take care of different functions:

Chemically active substances: Insulin is for instance a protein that twists a membrane bound protein (receptor) and
when this changes its form the effect is that it triggers a chemical reaction that makes the cellmembrane more
permeable and thus let glucose in.

The gated ionchannels (see cytology) are membrane bound proteins which are in rest twisted in such a way that the
channel is closed but they can be opened either under the influence of another molecule that interferes with its
Form (ligand gated channels) or by electric tension (voltage gated channels) when this happens the protein channel
twists and opens up a channel that connects directly with the cytoplasma of the cell. Many of the cellreceptors are
sugars but they are connected to the membrane and eventually with the interior of the cell by membrane bound
proteins that function like an anchor and transducer for the recptor. (see cytology)

Enzymes : are catalysators for almost all chemical reactions in our physiology and all them are proteins (see point

Messengers: hormones, neurotransmitters etc are often protids. This means that most regulation and coordination
functions are run by the means of the protid group! (As we will see later many substances are similar to these
messengers or block their receptors, that is why they are classified as endocrine disruptors. (****see addendum)

Proteïns as transportation-mode in our body

Many different proteins have a transporetfunction in our partly compartimented aquarium that we call body.
Haemoglobin , albumin and the apolipoproteïns are representative examples of this fact.
Haemoglobin is the transportmolecule par excellence for our gaseous exchanges between blood and outerworld or
between blood and tissue or cells. (O2 en CO2)


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M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Apolipoproteïns are the transportmolecules that help making a dry divingsuit for the strong hydrophobic fats or lipids
that have to be transported by the blood through the partly compartimented aquarium that we call body.
Albumin is a transporter for dangerous – poisoneous goods in our partly compartimented aquarium that we call body
(bilirubin for instance )

Proteïns as defensive mechanism

Two beautifull examples of proteins as defensive system are immunoglobulins and fibrin.
Immunoglobulins are attacking, immobilizing and inocculating bodystrange proteins, so that they can be destroyed and
disposed of by the Reticulo-Endothelial System (RES) .
(See later Liver-Spleen)
When the bloodvessel system is perforated by a stitch or cut, the bloodclotting is activated by protein transmitters, and
start to transform some other proteins for instance fibrinogene(protein) is polymerised into fibrin fibers that will patchup
and finally close the gap in the vessel.

Proteïns as reserve-substance or stash molecule

When the liver cannot deliver quickly enough glucose to the blood because the demand is too big, it turns to the stash
molecules: aminoacids are converted into glucose. (Hepato-neoglucogenesis )
If this is problematic because there is not enough food (sugars or aminoacids or fats) coming in through the portal
system the body will even start to break down muscleproteins to get enough stash to keep the system going. There are
many examples of this phenomenon but the most spectacular one, and best documented in my eyes is the case of the
Britisch S.A.S. soldier Chris Ryan during the First Gulfwar *)(* *see addendum)

Enzymes are biologic catalysators and thus vital proteins. If overheating for instance destroys enough enzymes the
whole of the physiology simply stops, all the substances may be there but they will not interact or transform. In such a
case the organism dies quickly. Catalysators
A catalysator is a chemical substance that accelerates, decelerates or simply makes a certain chemical reaction possible
under particular conditions. The specificity of catalysators is that the catalysator stays unaffected by the reaction in
which it intervenes. The consequence is that after the reaction, the catalysator is ready to do the job again, and again and
again. This is one of the reasons, why adults have a naturally slow production rate of internal enzymes; they simply last
long under normal conditions. Children that are still growing have much higher producing rates because their form
changes and mass increases constantly which demands a lot of metabolism.
Enzymes are biologic catalysators, in other words they make chemical reactions, transformations and so on possible
despite the conditions of temperature 37°C and the watery environment in humans. Practically all chemical reactions
demand a certain pressure, pH and temperature to happen spontaneously. But in a mammal these conditions are not or
far from perfect for all these individual reactions, so normally they could not happen unless, some specific enzyme
intervenes and catalyses the reaction. Characteristics and properties of enzymes and their catalytic reaction
In the year 1996, when I wrote this course, over two thousand enzymes were known and catalogized after their specif
catalytic reaction, divided into 6 specific classes. (see
Usually enzymes have workingspecifity as well as substrate specificity. Usually they need for their good performance
the help of co-enzymes. These characteristics are easily understood in combination with each other by the key-lock
theory. We will thus make good use of this theory as example and as synthesis.


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Workingspecifity of enzymes

What is meant with workingspecifity of an enzyme is: that each type of enzyme usually can only catalyse on type of
reaction. In other words it normally interacts only in one type of reaction. When we place this characteristic in the keylock theory, we get this parallelism: a key is made to open or close a lock and nothing else. Of cours yopu scratch your
back with it but you see what I mean, don’t you? As the enzyme the key once it has opened or closed the lock is ready to
work again, it comes unaffected out of the reaction. Only macroscopically of course, because as you all know after
many years of good service it will get used and won’t do the job anymore or breaks in the lock. This is agood
comparison, enzymesin adults have a slow production rate or a very slow turnover, almost as slow as the one with
which you have to change your keysets. (if you don’t loose them all the time at least)

Substrate specificity of enzymes

What is meant with substrate specificity of an enzyme is the characteristic that usually it only interacts with one
substance or substrate. This makes out that nearly for every type of substance you need another enzyme. This
characteristic is due to the form (shape) of the enzyme and is called spheric complementarity. There are enzymes that
are less specific and that can react with several comparable substances, but usually this concerns less complicated
reactions and the enzymes get worn out more quickly thus there turnover rate is higher.
Inour axample of the key-lock theory this matches also perfectly: a key usually only fits perfectly on a specific lock and
not on any lock (substrate specificity). Spheric compatibility is a perfect match the little teeth on the key adapt perfectly
to the negative in the lock. Substrate specificity can be seen as follows: proteins have a very specific spatial
organization as we have seen before, this is so specific that only few substrates match perfectly in the active part of the
enzyme (the active gap)
What about the less specific anzymes then where do they fit in the example? In French this type of keys are called “un
passe partout”. These keys function on different locks (poor substrate specificity) but usually they only function on easy
- unsuffisticated locks and as they are used a lot they wear down much faster, thus they must be replaced much faster
than a normal key. (Like the ones used in Hotels for instance)


Most enzymes are only really effective in their catalyzing reactions if they have enough coenzymes in their direct
environment. Coenzymes orient the enzymes in such a way that they are ready to fit the substrate. Most coenzymes are
vitamins or oligoelements.
Coenzymes on the other hand are not specific; one type of coenzyme can be used by different types of enzymes. In
reverse each enzyme needs its specific coenzyme to function properly.
If we return to our key-lock theory, we see that the best comparison for the coenzymes is our hand. Our hand can
manipulate different keys, but if we don’t grasp a key it will not get in the lock all by itself. Our hand orientates the key
in the right direction and makes it turn.

SYNTHESIS: The key-lock theory of E. Fischer 1894 .
When we recapitulate the key-lock theory for our mental eye and place all the pieces at the right place, enzymatic
catalysis turns out to be Childs’ play for as far as we need to understand it at least.
 The key with all its specifications: one site that is active (the gap) with its spheric compatibility and substrate
specificity and workingspecifity.
 The lock that is the substrate on which the key acts and that has at least one group that matches the other side of the
spheric compatibility.
 Turning the key in the lock which is the catalytic reaction on the substrate induced by the enzyme.
 After the reaction the enzyme is reutilisable because it is “hardly” worn or damaged by the reaction.

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M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

 Our hand is the coenzyme that orientates the key with its active gap in the right direction for the substrate. Denomination en categorization of the enzymes per class and properties

Denomination of the enzyme

Denomination of the enzymes is relatively simple, as well in the general as in the specific denomination. The general
name indicates the type of reaction they induce, and thus is used for the classes as well.
General rule for enzymatic denomination:
Action + Substrate specificity + ASE = NAME of the specific ENZYME
General chemical intervention + ASES = NAME of the ENZYMEGROUP-CLASS

Example with specific liver enzymes :
We have seen that in the Aa. some are non essential and can when necessary be reconverted in other types of non
essential Aa., this is of course done through enzymatic intervention.
Class: TRANSFERASES (enzymes that do a transfer of a group)
Group: TRANSAMINASES (enzymes that transfer an amine containing group N)
Specific: ASPARTAAT TRANSAMINASE (three letter word GOT )
Or for instance ALANINE TRANSAMINASE (three letter word GPT ) this will come back in bloodtests, classic liver

Classification of enzymes

Class 1: OXIDO-REDUCTASES: catalyse reduction reactions, reactions in which an enzyme catalyzes the transfer of
electrons from one molecule (the reductant, also called the hydrogen acceptor or electron donor) to another (the oxidant,
also called the hydrogen donor or electron acceptor). (Taken away from one molecule and added to another)
Groups: Oxidases , peroxidases , reductases , mono-oxygenases , dehydrogenases etc.
Class 2: TRANSFERASES: catalyse transfer reactions, transfers from groups.
Groups: Transaminases, aminotransferases, fosfotransferases, glycosyltransferases etc.
Class 3: HYDROLASES: Catalyse evenso transfer reactions but in which there is always a watermolecule in play, the
acceptor takes the water.
Groups: Peptidases, glycosidases, esterases, carboxy-exopeptidases etc.
Class 4: LYASES: catalyse a bondingreaction that usually is accompagnied by the genesis or break down of double or
triple bonds; these groups are denominated after the atoms on which they interact.
Groups: C S lyases, C O lyases, C N lyases, C C lyases etc.
Class 5: ISOMERASES: catalyse isomerisation reactions: they deplace chemical groups within the same molecule
without changing the bruto totalformula of the molecule.
Groups: Trans-isomerases, cys-isomerases, intramolecular transferases etc.
Class 6: LIGASES (old terminology = synthetases): catalyse a bindingreaction that costs energy. (Ligare = Latin for
binding or tying). These enzymes synthetize new products, by the combination of two components and binding them

Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

together into one molecule. This binding activity costs energy and thus always goes together with ATPase activity
(breaking ATP down into ADP + P + Energy) The groupsnames are given depending on the substances between which
they make a bond. Groups: C S ligases, C O ligases, C N ligases, C C ligases etc. List of some of the most important coenzymes

List of the most important vitamines that function as coenzymes.

Vitamin A : Necessary for cellular growth of all tissues, the synthesis of steroidhormones and anti-oxidative function.
Retinol (vitamin A)
-carotene (provitamin A which is enough to make 2 vitamins A)
Vitamin B1 : Has many functions especially for the heart and nervous system.
Vitamin B2 : Especially used in oxidationreactions.
Vitamin B3 : has many functions for instance for cholesterolmetabolism, steroidhormon- production and the nervous
Nicotinic acid (niacin )
Vitamin B5 : Essentially used in the carbohydrate and lipid metabolism and in the synaptic transmission (coenzym A
and steroidmetabolism)
Pantothenic acid
Vitamin B6 : Has many functions for instance, nervous system, immune system and prostaglandinsynthesis.
Vitamin B12 : Is essential in DNA synthesis and the myelinisation process of the nerves.
Biotin : actually a cofactor for some vitamins of the B series.
Folic acid : is a cofactor which is mainly used in the synthesis of DNA and the riping of the erythrocytes (red blood
Vitamin C : Many functions: antioxidant, connective tissue or collagen synthesis, adrenalin production and elimination
of free radicals (cancerinogenic substances), help for the imunesystem etc.
Ascorbic acid
Vitamin D : extremely important for the calcium metabolism regulation.
calciferol (cholecalciferol )
Vitamine E : antioxidant, stimulation of the reproductive glands and elemination of free radicals (such as nitrosamins),
stimulates the oxygen distribution on a cellular level.
Bioflavanoïds : antioxidants reinforce the activity of Vit. A,E,C and improve the solidity of the cappilary walls and
their permeability.
Oligomere procyanids


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M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

List of the most important oligoelements that help as coenzymes.

Calcium : next to cellcommunication, skeleton rigidification is Ca an important coenzyme for several enzymegroups.
Cobalt : very important in the kidneyfunctiion and the physiology of the autonomous nerve system, essential for B12.
Chroom : supportive element for the intervention of insulin (glucose tolerance factor)
Phosphor : important cofactor for the B vitamins and the parathyroid gland.
Fluor : Ca metabolism and quality of the connective tissue
Jodium : essential for the thyroidglands’ function
Kalium or Potassium : nerve potential and conduction, heartbeat regulation, water and acid household
Cupper : is an important cofactor in the immunesystem, for the iron uptake and antioxidative enzymes.
Magnesium : cofactor for the vitamins B and C & several metabolic processes.
Selenium : antioxidative effect, is necessary for the production of enzymes that manage the peroxid metabolism.
Zinc : many functions in the liver, central nervous system, prostate and prostaglandin production, skin etc.
Sulfur : essential in protein metabolism and bilary production.

1.1.5. NUCLEÏC ACIDS, NUCLEOTIDS AND BASES Introduction and short history
Nucleic acids got their name because at their first discovery they were extracted of a cell nucleus. Later it was
discovered that they are not only restricted to the cell nucleus, but the name in use was kept. (As is mostly the case in
sciences, which complicate unnecessarily and sometimes even instaures false idees in time, see anatomy dural
terminology.) The nucleic acids are the central actors in the mechanism of keeping record of the transmissible
characteristics of a species and line of individuals. The nucleic acids are also essential in bringing to expression these
characteristics by their commanding role in the proteinsynthesis. Nucleic acids have a little similarity in their complexity
with proteins. Like proteins they are a chainlike huge mmolecule that is build up by segments that are linked together in
a very specific way. In the proteins we saw that the segments are Aa.; in nucleic acids they are constituted by
nucleotids. The nucleotides are constituted by the combination of a base and a pentose. (see carbohydrates)
This part of the biochemistry and genetics is still in full speed development and new applications arise almost on a
weekly basis that makes it impossible to follow up closely. For the practical side of Osteopathy however this is not of
vital importance. Let us just try to have an idea of the general line of the science and cultural history attached to it
because that is certainly of philosophical importance, I think.
Historically this science is really a newcomer that opens Pandora’s Box regulary:
 1822-1884: Mendel discovers the laws of heredity through his bean experiments.
 1859: Darwin publishes his “On the origin of species”
 1869: Mieschner discovers DNA after its extraction of a cell nucleus (nucleïc acid)


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M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

 1925-1930: Levene discovers the structure of mononucleotids , and prooves that they are the fundamental building
segments of the nucleic acidchain.
 1944: Avery, MacLeod and McCarty can link bacterial transformation (mutation) and the nucleic acid that changed.
 1952-1954: Zamecnik et al discover that the ribosomes are the place in the cell where proteinsynthesis takes place.
 1953: Watson & Crick come with the model that DNA would be a double helix structure . (What was later proven
 1955: Benzer comes with the first genetic carthography & discovers that genes can be translocated (displaced) .
 1956: Kornberg discovers the enzyme DNA polymerase
 1957: Hoagland, Zamecnik and Stephenson succeed to isolate T-RNA and explain its function.
 1958: Meselson and Stahl give the experimental confirmation of Watson & Crick’s model of the DNA and its
 1958-1959: Weiss and Hurwitz discover the DNA aimed RNA polymerase .
 1960: Hirs, Moore and Stein discover the Aa. sequence of ribonuclease.
 1961: Jacob and Monod the function of M-RNA in the proteÏnsynthesis.
 1961-1965: The labs of Nirenberg, Khorana and Ochoa discover the genetic code three letter words or triplets that
define an Aa. Since then labs all over the world worked together to find the human genome (The human genome

Rosalind Franklin (1920 - 1958)
David Ardell
By 1952, much was known about DNA, including its exclusive role as genetic material – the sole
substance capable of storing practially all the information needed to create a living being. What
was not yet known was what the elusive DNA molecule looked like, or how it performed this
amazing hereditary function. This would change in the course of a single year. The now familiar
double helical structure of DNA, a twisted ladder with base-pairs rungs essential to its hereditary
function, was deciphered in 1953. The individuals most commonly associated with this remarkable
accomplishment are James Watson and Francis Crick. Maurice Wilkins played a role as well, for
which he shared the 1962 Nobel Prize for Physiology and Medicine with Watson and Crick. Yet
there was one other person whose truly essential contribution to this discovery could not be
recognized by the Nobel Committee in 1962. That person was Rosalind Franklin.
Born in July of 1920, Rosalind Franklin graduated with a Ph.D. from Cambridge University in 1945. In 1951, she went
to work as a research associate for John Randall at King's College in London. A chemist by training, Franklin had
established herself as a world expert in the structure of graphite and other carbon compounds before she moved to
London. In James Watson's account of the discovery of the structure of DNA, entitled The Double Helix, Rosalind
Franklin was depicted inaccurately as an underling of Maurice Wilkins at King's College. In fact, Maurice Wilkins and
Rosalind Franklin were peers. Franklin had discovered that DNA could crystallize into two different forms, an A form
and a B form. John Randall gave Franklin the A form and Wilkins the B form, assigning them each the task of
elucidating their molecular structure.
The technique with which Wilkins and Franklin set out to do this is called X-ray crystallography. With this technique a
crystal is exposed to x-rays in order to produce a diffraction pattern. If the crystal is pure enough and the diffraction
pattern is acquired very carefully, it is possible to reconstruct the positions of the atoms in the molecules that comprise


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M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

the basic unit of the crystal called the unit cell. By the early 1950s, scientists were just learning how to do this for
biological molecules as complex as DNA. Progress in discerning the structure of DNA was blocked because the A and B
forms of DNA were mixed together in preparations, yielding impure crystals and "muddy" diffraction patterns that were
near impossible to interpret.
After discovering the existence of the A and B forms of DNA, Rosalind Franklin also succeeded in developing an
ingenious and laborious method to separate the two forms, providing the first DNA crystals pure enough to yield
interpretable diffraction patterns. She then went on to obtain excellent X-ray diffraction patterns of crystalline B-form
DNA and, using a combination of crystallographic theory and chemical reasoning, discovered important basic facts
about its structure. She discovered that the sugar-phosphate backbone of DNA lies on the outside of the molecule, not
the inside as was previously thought. She discovered the helical structure of DNA has two strands, not three as proposed
in competing theories. She gave quantitative details about the shape and size of the double helix. The all- important
missing piece of the puzzle that she could not discover from her data was how the bases paired on the inside of the helix,
and thus the secret of heredity itself. That discovery remained for Watson and Crick to make.
After Randall presented Franklin's data and unpublished conclusions at a routine seminar, aspects of her results were
informally communicated to Watson and Crick by Maurice Wilkins and Max Perutz, without her or John Randall's
knowledge. It was Watson and Crick who put all the pieces of the puzzle together from a variety of sources including
Franklin's results, to build their ultimately correct and complete description of DNA's structure. Their model for the
structure of DNA appeared in the journal Nature in April, 1953, alongside Franklin's own report.
Rosalind Franklin never knew that Watson and Crick had gotten access to her results. At the time of the Watson and
Crick publication and afterwards, Franklin appears not to have been bitter about their accomplishment. In her own
publications about DNA structure, she agreed with their essential conclusions but remained skeptical about some details
of their model. Franklin moved on to work on an even more challenging problem: the structure of an entire virus, called
the Tobacco Mosaic Virus. Her subsequent publications on this topic would include four more papers in the journal
Nature. Rosalind Franklin was friendly with both James Watson and Francis Crick, and communicated regularly with
them until her life and career were cut short by cancer in April of 1958, at the age of 37. She died with a reputation
around the world for her contributions to knowledge about the structure of carbon compounds and of viruses. After her
death, Watson and Crick made abundantly clear in public lectures that they could not have discovered the structure of
DNA without her work. However, because the Nobel Prize is not awarded posthumously, Rosalind Franklin could not
be cited for her essential role in the discovery of the physical basis of genetic heredity.

Maddox, B. (2003). The double helix and the `wronged heroine. Nature 421:407.

Lightman, A. (2005). The Discoveries. Pantheon Books, New York. Pp. 356 - 379.

As we worked our way through in a complexifying chronology, we will mainatain this for the nucleic acids although it is
almost the contrary of the discovery chronology.

1.1.6. BASES
The bases that are a part of the construction segments (nucleotids ) of the nucleic acids are derivates of two molecules:
pyrimidin and purin.
Therefore they are divided in two groups the pyrimidin bases and the purin bases.
These bases are the building blocks for the nucleotids of all living organisms on this planet. Pyrimidin bases
Pyrimidin is a ringlike hexagonal molecule that contains Nitrogen. The derived molecules that we find back as the the
codes for the aminoacids and as link or nucleotide are:
 Uracil

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M.Girardin D.O., Evost Fellow, Pro-sector
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 Thymin
 Cytosin
When speaking in genetic coding system only the first letters are used: U, T, C
Cytosin is used as well for DNA as for RNA.
Thymin only for DNA
Uracil only for RNA.
As we see later U and T are the same, in other words they match the same purin base but U is exclusive for the RNA
,while T is used in DNA . Purin bases
Purin is a double ringstructure that contains twice as much
Nitrogen groups as a pyrimidin base. The derived molecules that
function as constructing segments nucleotids are:
 Adenin
 Guanin
Both are in use for DNA and RNA codes. (Nucleotids)

In order to build a nucleosid or nucleotid the bases will be linked to a sugar (pentose ) fior instance the bond between a
purinbase Adenine and the pentose Ribose generates the nucleosid: Adenosin. (Code A.)
These nucleosids are not only in use for the genetic encoding they are the most important basis for our intracellular
energy providing system too. When a phosphategroup (P) is added to this nucleoside it turns into a nucleotid:
Adenosin monophosphate or AMP


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M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Two phosphate bonds make ADP
When a third is joined we get ATP
In the same way other bases-pentoses (nucleosids synthesis) can be added; and than later phosphategroups (nucleotides
-adenosin (A)
-guanosin (G)
-uridin (U)
-thymidin (T)
-cytidin (C)

When several nucleotids are alined they can bond through their phosphategroups. This is how a polynucleotide is
formed: a dinucleotid , than a trinucleotid and in the run a polynucleotid . This polynucleotid forms a real chain where
the spine is formed by sugars and their phosphate groups that link. On the side they will present their bases in a row: for
The oldest phylogenetic form of polynucleotid is RNA. Once this form of complexity was generated, the road to quick
biologic evolution was open. ( Do not forget that RNA itself is a product of evolution)


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M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015 DNA

DNA was probably generated later and can be seen as the next step in complexity
increase: The DNA double Helix can be interpreted as two RNA like chains that join like a
stepladder, but with a much longer sequence of codes.
And of course not to forget that Uracil, present in RNA is replaced by Thymin in the DNA
chain and stepladder. Functions of polynucleotids

The polynucleotids RNA and DNA are the recorders of the genetic information, or the
exact definitionlogs of the Aa. sequences for polypeptids and proteins (***** see
addendum) This makes it possible to reconstruct a part of the story of living organisms
and their genetic relationship. (interesting and very readable examples: Brian Sykes, the
seven daughters of Eve, about the relationship between mitochondrial DNA and the
spreading of the homo sapiens sapiens over the world.)
The rest of this story is told in cytology and proteinsynthesis.
Figure 16 Schematic representation of the Bases

Figure 17 Schematic representation of a nucleosid


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M.Girardin D.O., Evost Fellow, Pro-sector
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Figure 18 Schematic representation of a nucleotid

Figure 19 Schematic representation of the construction of A POLYNUCLEOTID

Figure 20 Schematic representation of the DNA double helix


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

This schema is the three dimensional representation of the Figures 12 and 13 of the  pleeted sheet configuration of


Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Addendum Protein folding problem
Protein folding
From Wikipedia, the free encyclopedia

Protein folding is the physical process by which a polypeptide folds into its characteristic three-dimensional structure.
Each protein begins as a polypeptide, translated from a sequence of mRNA as a linear chain of amino acids. This
polypeptide lacks any developed three-dimensional structure (the left hand side of the neighboring figure). However
each amino acid in the chain can be thought of having certain 'gross' chemical features. These may be hydrophobic,
hydrophilic, or electrically charged, for example. These interact with each other and their surroundings in the cell to
produce a well-defined, three dimensional shape, the folded protein (the right hand side of the figure), known as the
native state. The resulting three-dimensional structure is determined by the sequence of the amino acids. The mechanism
of protein folding is not completely understood.
Experimentally determining the three dimensional structure of a protein is often very difficult and expensive. However
the sequence of that protein is often known. Therefore scientists have tried to use different biophysical techniques to
manually fold a protein. That is, to predict the structure of the protein complete from the sequence of the protein.
For many proteins the correct three dimensional structure is essential for the protein to function correctly. Thus "failure"
of folding usually produces inactive proteins with different properties, details can be found under Prions. Several
diseases are believed to result from the accumulation of misfolded proteins, e.g. Alzheimer's disease, cystic fibrosis and
Known facts about the process
The relationship between folding and amino acid sequence
Most folded proteins have a hydrophobic core in which side chain packing stabilizes the folded state, and charged or
polar side chains on the solvent-exposed surface where they interact with surrounding water molecules. It is generally
accepted that minimizing the number of hydrophobic sidechains exposed to water is the principal driving force behind
the folding process , although a recent theory has been proposed which reassesses the contributions made by hydrogen
The process of folding in vivo often begins co-translationally, so that the N-terminus of the protein begins to fold while
the C-terminal portion of the protein is still being synthesized by the ribosome. Cells express specialized proteins called
chaperones whose function is to aid in the folding of other proteins. A major example is the bacterial GroEL system,
which assists in the folding of globular proteins. In eukaryotic organisms chaperones are known as heat shock proteins.
Although most globular proteins are able to assume their native state unassisted, chaperone-assisted folding is necessary
for some proteins in the crowded intracellular environment to prevent aggregation; chaperones are also used to prevent
misfolding and aggregation which may occur as a consequence of exposure to heat or other changes in the cellular
environment. The particular amino-acid sequence (or "primary structure") of a protein predisposes it to fold into its
native conformation or conformations. Proteins do so spontaneously during or after their synthesis inside cells. While
these macromolecules may be seen as "folding themselves," their folding depends on the characteristics of their
surrounding solution, including the identity of the primary solvent (either water or lipid inside cells), the concentration
of salts, the temperature, and molecular chaperones.
For the most part, scientists have been able to study many identical molecules folding together en masse. At the coarsest
level, it appears that in transitioning to the native state, a given amino acid sequence takes on roughly the same route and
proceeds through roughly the same intermediates and transition states. Often folding involves first the establishment of
regular secondary and supersecondary structures, particularly alpha helices and beta sheets, and afterwards tertiary
structure. Formation of quaternary structure usually involves the "assembly" or "coassembly" of subunits that have
already folded. The regular alpha helix and beta sheet structures fold rapidly because they are stabilized by
intramolecular hydrogen bonds, as was first realized by Linus Pauling. Protein folding may involve covalent bonding in
the form of disulfide bridges formed between two cysteine residues or formation of metal clusters. Shortly before
settling into their more stable native conformation, molecules may pass through an intermediate "molten globule" state.


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The essential fact of folding, however, remains that the amino acid sequence of each protein contains the information
that specifies both the native structure and the pathway to attain that state: Folding is a spontaneous process. The
passage of the folded state is mainly guided by the hydrophobic interactions, formation of intramolecular hydrogen
bonds, and van der Waals forces, and it is opposed by conformational entropy of the polypeptide chain.
Preconditions for correct folding
In certain solutions and under some conditions proteins will not fold into their biologically "functional" forms.
Temperatures above the range that cells tend to live in will cause proteins to unfold or "denature" (this is why boiling
makes the white of an egg opaque). High concentrations of solutes and extremes of pH can do the same. A fully
denatured protein lacks both tertiary and secondary structure, and exists as a so-called random coil. Cells sometimes
protect their proteins against the denaturing influence of heat with enzymes known as chaperones or heat shock proteins,
which assist other proteins both in folding and in remaining folded. Some proteins never fold in cells at all except with
the assistance of chaperone molecules, that either isolate individual proteins so that their folding is not interrupted by
interactions with other proteins or help to unfold misfolded proteins, giving them a second chance to refold properly.
Incorrect protein folding and neurodegenerative disease
Incorrectly folded (misfolded) proteins are responsible for prion related illness such as Creutzfeldt-Jakob disease and
Bovine spongiform encephalopathy (mad cow disease), and amyloid related illnesses such as Alzheimer's Disease.
These diseases are associated with the aggregation of misfolded proteins into insoluble plaques; it is not known whether
the plaques are the cause or merely a symptom of illness.
Time scales of protein folding and the Levinthal paradox
The entire duration of the folding process varies dramatically depending on the protein of interest. The slowest folding
proteins require many minutes or hours to fold, primarily due to steric hindrances. However, small proteins, with lengths
of a hundred or so amino acids, typically fold on time scales of milliseconds. The very fastest known protein folding
reactions are complete within a few microseconds. The Levinthal paradox, proposed by Cyrus Levinthal in 1969, states
that, if a protein were to fold by sequentially sampling all possible conformations, it would take an astronomical amount
of time to do so, even if the conformations were sampled at a rapid rate (on the nanosecond or picosecond scale). Based
upon the observation that proteins fold much faster than this, Levinthal then proposed that a random conformational
search does not occur in folding, and the protein must, therefore, fold by a directed process.
The "reverse" of the folding process is called protein denaturation, whereby the native structure of a protein is disrupted
and a random coil ensemble of unfolded structures is formed instead. Denaturation can be carried out chemically by the
addition of denaturants or thermally by heating (and sometimes cooling). Many denatured proteins precipitate into
insoluble amorphous aggregates. Some proteins denatured under some conditions can reversibly refold; however, in
many cases denaturation is irreversible. Folding and unfolding rates also depend on environment conditions like
temperature, solvent viscosity, pH and more. The folding process can also be slowed down (and the unfolding sped up)
by applying mechanical forces, as revealed by single-molecule experiments.

Worldwide Pandemics
165-180: Antonine Plague, perhaps smallpox
541: the Plague of Justinian
1300s: the Black Death
1501-1587: typhus
1732-1733: influenza
1775-1776: influenza
1816-1826: cholera
1829-1851: cholera
1847-1848: influenza
1852-1860: cholera
1855-1950s: bubonic plague: Third Pandemic
1857-1859: influenza
1863-1875: cholera
1889-1892: influenza
1899-1923: cholera
1918: avian flu: Spanish flu: more people were hospitalized in World War I from this epidemic than wounds. Estimates
of the dead range from 20 to 40 million worldwide (WHO)
1960s: cholera called El Tor

Physiology: Introduction
M.Girardin D.O., Evost Fellow, Pro-sector
1995, reeditions 2007, 2014, 2015

Spanish flu
From Wikipedia, the free encyclopedia
(The 1918 flu pandemic, commonly referred to as the Spanish flu, was a category 5 influenza pandemic between 1918
and 1920 caused by an unusually severe and deadly Influenza A virus strain of subtype H1N1. By far the most
destructive pandemic in history, it killed some 50 million to 100 million people worldwide in just 18 months, dwarfing
the bloodshed due to World War I (1914-1918). Many of its victims were healthy young adults, in contrast to most
influenza outbreaks which predominantly affect juvenile, elderly, or otherwise weakened patients.
The disease was first observed at Fort Riley, Kansas, U.S. on March 11, 1918. One researcher argues that the disease
was found in Haskell County, Kansas as early as January of 1918. The Allies of World War I came to call it the Spanish
Flu, primarily because the pandemic received greater press attention in Spain than in the rest of the world, as Spain was
not involved in the war and had not imposed wartime censorship.
Scientists have used tissue samples from frozen victims to reproduce the virus for study. Given the strain's extreme
virulence and the possibility of accidental escape (or deliberate release) from quarantine, there has been controversy
regarding the wisdom of such research. Among the conclusions of this research is that the virus kills via a cytokine
storm, which explains its unusually severe nature and the unusual age profile of its victims.
The global mortality rate from the 1918/1919 pandemic is not known, but is estimated at 2.5 – 5% of the human
population, with 20% of the world population suffering from the disease to some extent. Influenza may have killed as
many as 25 million in its first 25 weeks; in contrast, AIDS killed 25 million in its first 25 years. Some estimates put the
total killed at over twice that number, possibly even 100 million.
An estimated 17 million died in India, about 5% of India's population at the time. In the Indian Army, almost 22% of
troops who caught the disease died of it. In the U.S., about 28% of the population suffered, and 500,000 to 675,000
died. In Britain 200,000 died; in France more than 400,000. Entire villages perished in Alaska and southern Africa. In
Australia an estimated 10,000 people died and in the Fiji Islands, 14% of the population died during only two weeks,
and in Western Samoa 22%.
While World War I did not cause the flu, the close quarters and mass movement of troops quickened its spread.
Researchers speculate that the soldiers' immune systems were weakened by the stresses of combat and chemical attacks,
increasing their susceptibility to the disease.
A large factor in the spread of the disease was the increased amount of travel. The modernization of transportation made
it easier for sailors to spread the disease more quickly and to a wider range of communities.
Patterns of fatality
The influenza strain was unusual in that this pandemic killed many young adults and otherwise healthy victims - typical
influenzas kill mostly infants (aged 0-2 years), the old, and the immunocompromised. Another oddity was that this
influenza outbreak struck hardest in summer and fall (in the Northern Hemisphere). Typically, influenza is worse in the
winter months.
People without symptoms could be struck suddenly and within hours be too feeble to walk; many died the next day.
Symptoms included a blue tint to the face and coughing up blood caused by severe obstruction of the lungs. In some
cases, the virus caused an uncontrollable hemorrhaging that filled the lungs, and patients drowned in their body fluids.
In fast-progressing cases, mortality was primarily from pneumonia, by virus-induced consolidation. Slower-progressing
cases featured secondary bacterial pneumonias, and there may have been neural involvement that led to mental disorders
in a minority of cases. Some deaths resulted from malnourishment and even animal attacks in overwhelmed
JAOA • Vol 104 • No 10 • October 2004 • 406-407

Harold I. Magoun, Jr, DO, FAAO, FCA, DO ED (Hon)
In his letter, Martyn E. Richardson, DO, was absolutely right in advocating the use of osteopathic manipulative treatment
(OMT) for patients with severe acute respiratory syndrome (J Am Osteopath Assoc. 2004;104: 71). However, although
Dr Richardson cited the influenza epidemic of 1918 as a reference, he did not provide related statistics. As that event is
the most outstanding example of the efficacy of OMT on record in the United States, related statistics have been

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