Biochemicals.
Atomic composition of the body.
Of the 108 chemical elements only 24, are known to be essential,
for the structure and functioning of the human body.
In fact only 4 of these elements - hydrogen, oxygen, carbon and nitrogen -
account for 99% of the body’s atoms.
Seven mineral elements are the most abundant substances,
dissolved in intracellular and extracellular fluids.
They are calcium, phosphorus, potassium, sulphur, sodium, chlorine and magnesium.
They comprise of 0.7% of the total atoms.
Most of the calcium and phosphorus atoms make up the solid structure of bone tissue.
13 other elements are trace elements, which are present in extremely small quantities.
They comprise less than 0.01% of the atoms.
They are however essential for life.
For example, iron a trace element plays a critical role in the transport of oxygen by the blood.
Apart from the 24 elements, the other elements detected in the body enter through the food we eat,
and the air we breathe.
These additional elements do not have any known chemical functions.
Some of them like mercury could be toxic to the body.
Molecules.
Two or more atoms bonded together make up a molecule.
For example, a molecule of water contains two hydrogen atoms and one oxygen atom,
and is written as H2O.
The atomic composition of glucose, a sugar is C6H12O6.
It indicates that glucose molecule has 6 carbon atoms, 12 hydrogen atoms and 6 oxygen atoms.
Such formulas do not indicate which atoms are linked to which in the molecule.
Covalent chemical bonds.
The atoms in molecules are held together by chemical bonds.
These are formed when electrons are transferred from one atom to another,
or are shared between two atoms.
A covalent bond, the strongest chemical bond between two atoms,
is formed when one electron in the outer electron orbit of each atom is shared between the two atoms.
The atoms in most molecules found in the body are linked by covalent bonds.
The atoms of some elements can form more than one covalent bond,
and thus can become linked simultaneously to two or more atoms.
Each type of atom has a characteristic number of covalent bonds that it can form,
that depends on the number of electrons present in the outer most orbit.
The number of chemical bonds formed by the four more abundant atoms in the body are,
hydrogen-1,
oxygen-2,
nitrogen-3,
carbon-4.
A water molecule can be illustrated as H-O-H.
In some cases, two covalent bonds - a double bond - are formed between two atoms,
when two electrons from each atom are shared.
An example of this is carbon dioxide, CO2.
It is represented as O=C=O.
We can note that in this molecule the carbon atom still forms four covalent bonds,
and each oxygen atom only two.
Molecular shape.
When atoms are linked together, molecules with various shapes can be formed.
Although we represent them diagrammatically in two dimensions,
they have actually three dimension shapes.
When more than one covalent bond is formed with the given atom,
the bonds are distributed about the atom in a pattern, that may or may not be symmetrical.
Molecules are not rigid, inflexible structures.
Within certain limits, the shape of a molecule can be changed, without breaking the covalent bonds,
linking its atoms together.
A covalent bond is like an axle, around which joint atoms can rotate.
The three dimensional shape of molecules is one of the major factors governing molecular interactions.
Ions.
An atom is electrically neutral since it contains equal number of negative electrons and positive protons.
If, however, an atom gains or loses one or more electrons,
it acquires a net electric charge and becomes an ion.
For example, when the sodium atom, which has 11 electrons, loses one electron,
it becomes a sodium ion, Na+, with a positive charge.
A chlorine atom which has 17 electrons, can gain an electron and become a chloride ion,
Cl-, with a net negative charge.
Some atom can gain or lose more than one electron,
to become ions with two or even three units of electrical charge, example, calcium, Ca+2.
Because of their ability to conduct electricity when dissolved in water,
ions are collectively known as electrolytes.
Hydrogen atoms and most of the mineral and trace elements readily form ions,
whereas carbon, oxygen, and nitrogen do not.
The number of electrons an atom may gain or lose in becoming an ion,
is a specific characteristic of each type of atom.
Ions that have positive charge are called cations.
Ions that have negative charge are called anions.
The process of ion formation, known as ionisation can occur in single atoms, or in molecules.
Two commonly encountered groups of atoms within molecules that undergo ionisation,
are the carboxyl group, — COOH, and amino group, — NH2.
The carboxyl group ionises when the oxygen atom linked to the carbon atom,
captures the hydrogen atom’s only electron to form a carboxyl ion, R—COO-, and a hydrogen ion H+.
R—COOH --> R—COO-, + H +.
The amino group can bind an hydrogen ion to form an ionised amino group, R—NH3 +.
R—NH2 + H + —> R—NH3 +.
The ionisation of the each of the groups can be reversed.
The ionised carboxyl group can lose an hydrogen ion to form a unionised carboxyl group.
The ionised amino group can lose an hydrogen ion to become a unionised amino group.
Polar molecules.
When the electrons of two atoms interact, the two atoms may share the electrons equally,
forming an electrically neutral covalent bond, or one of the atoms may completely capture,
an electron from the other atom, forming ions.
Between these two extremes there exists covalent bonds in which the electrons are not shared equally, between the two atoms, but instead reside closer to one atom of the pair.
The atom thus acquires a slight negative charge, while the other atom having partly lost an electron,
becomes slightly positive.
Such bonds are known as polar covalent bonds,
since the atoms at each end of the bond have a slightly different electric charge.
Polar bonds do not have a net electric charge, as do ions,
since they contain equal amounts of negative and positive charge.
For example, the bond between hydrogen and oxygen in a hydroxyl group, R— OH,
is a polar covalent bond, in which the oxygen is slightly negative and the hydrogen is slightly positive.
The electric charge associated with the ends of a polar bond is considerably less,
than the charge of a fully ionised atom.
For example, the oxygen in the polarised hydroxide group has only about 13% of the negative charge, associated with the oxygen in ionised carboxyl group, R—COO-.
Atoms of oxygen and nitrogen, which have a strong attraction for electrons,
form polar bonds with hydrogen atoms.
The bond between carbon and hydrogen atoms,
and that between two carbon atoms are electrically neutral.
A single molecule may contain non polar, polarised,
and ionised bonds in different regions of the molecule.
Molecules containing significant number of polar bonds or ionised groups are called polar molecules.
Molecules composed predominately of electrically neutral bonds are known as non polar molecules.
The physical characteristics of these two classes of molecules, especially their solubility in water,
are quite different.
Hydrogen bonds.
The electrical attraction between the hydrogen atom in one polarised bond,
and the oxygen or nitrogen atom in a polarised bond of another molecule - or within the same molecule, if the bonds are sufficiently separated from each other - forms a hydrogen bond.
This type of bond is much weaker than a covalent bond.
It is only about 4% of the strength of the covalent bonds linking the hydrogen and oxygen,
within a water molecule, H2O.
Hydrogen bonds between and within molecules play an important role in molecular interactions,
and in determining the shape of larger molecules.
Water.
Hydrogen is the most numerous atom in the body.
Water is the most numerous molecule in the body.
Out of every 100 molecules, 99 are water.
The covalent bonds linking the two hydrogen atoms to the oxygen atom, in a water molecule are polar.
Therefore, the oxygen in the water have a slightly negative charge,
and each hydrogen atom has a slightly positive charge.
The positively polarised region near the hydrogen atom of one water molecule,
are electrically attracted to the negatively polarised regions of the oxygen atom,
in adjacent water molecules, forming hydrogen bonds.
At body temperature,
the hydrogen bonds between water molecules are continuously being formed and broken,
accounting for the liquid state of water.
If the temperature is lowered, these hydrogen bonds are less frequently broken,
and larger and larger clusters of water molecules are formed,
until at 0 degrees celsius water freezes into a continuous crystalline matrix - ice.
Water molecules take part in many chemical reactions of the general type :
R1—R2 + H—O—OH —> R1—OH + H—R2.
In this reaction the covalent bond between R1 and R2,
and the covalent bond between a hydrogen atom and oxygen in water is broken,
and the hydroxyl group and hydrogen atom are transferred to R1 and R2, respectively.
Reactions on this type are known as hydrolytic reactions or simply hydrolysis.
Many large molecules in the body are broken down into smaller molecular units by hydrolysis.
Solutions.
Substances dissolved in a liquid are known as solutes.
The liquid in which they are dissolved is the solvent.
Solutes dissolved in a solvent form a solution.
Water is the most abundant solvent in the body, accounting for 60% of the total body weight.
A majority of the chemical reactions that occur in the body involve molecules,
that are dissolved in water - either in the intracellular or extracellular fluids.
However, not all molecules dissolve in water.
Molecular stability.
In order to dissolve in water, a substance must be electrically attracted to water molecules.
For example, table salt is a solid crystalline substance,
because of the strong electrical attraction between positive sodium ions and negative chloride ions.
This strong attraction between two oppositely charged ions is known as an ionic bond.
When a crystal of sodium chloride is placed in water,
the polar water molecules are attracted to the charged sodium and chloride ions.
The ions becomes surrounded by clusters of water molecules,
allowing the sodium and chloride ions to separate from the salt crystal, and enter the water,
that is to dissolve.
Molecules having a sufficient number of polar bonds and/or ionised groups will dissolve in water.
Such molecules are said to be hydrophilic - water loving.
Thus, in a molecule, the presence of ionised carboxyl and amino groups promotes solubility in water.
In contrast, molecules composed predominantly of carbon and hydrogen are insoluble in water,
since there electrically neutral covalent bonds are not attracted to water molecules.
These molecules are hydrophobic - water fearing.
When non polar molecules are mixed with water, two phases form,
as occurs when oil is mixed with water.
The strong attraction between polar water molecules “squeezes” the non polar molecules,
out of the water phase.
Such a separation is never 100% complete, however,
and very small amounts of non polar solutes remain dissolved in water.
Although non polar molecules do not dissolve to any great extent in water,
they will dissolve in non polar solvents, such as carbon tetrachloride.
Molecules that have a polar or iodised region at one end and a non polar region at the opposite end,
are called amphipathic - consisting of two parts.
When mixed with water, amphipathic molecules form clusters, such that their polar hydrophilic regions, are located at the surface of the cluster, where they are attracted to the surrounding water molecules,
and non polar hydrophilic ends are oriented towards the interior of the cluster.
Such an arrangement provides a maximal interaction between the water molecules,
and the polar end of the amphipathic molecules.
Long polar molecules can dissolve in the central non polar regions of these clusters,
and thus be carried in aqueous solutions in far higher amounts,
then would otherwise be possible based on their low solubility in water.
The orientation of amphipathic molecules plays an important role in the structure of cell membranes,
and in both the absorption of non polar molecules from the gastrointestinal tract,
and their transport in blood.
Concentration.
Solute concentration is defined as the amount of solute present in a unit volume of solution.
One way of expressing the amount of a substance is to give its mass in grams.
Its concentration can then be expressed as the number of grams of the substance,
present in a litre of solution - grams per litre - g/L.
A comparison of the concentration of two different substances,
on the basis of number of grams per litre of solution,
does not directly indicate how many molecules of each compound are present.
When the structure of a molecule is known, concentrations are expressed as moles per litre,
which provides a unit of concentration based upon the number of molecules of the solute in the solution.
The molecular mass of a molecule is equal to the sum of the atomic masses,
of all the atoms in the molecule.
For example, glucose C6H12O6, has a molecular mass of 180.
One mole (or mol, or 1M) of a substance is the amount of the substance in grams,
equal to its molecular mass.
Accordingly the solution containing 180 grams of glucose in one litre of solution,
is said to be one-molar solution of glucose, or 1 mol/L.
Just as 1gram atomic mass of any element contains the same number of atoms,
1 gram molecular mass (1 mole) will have the same number of molecules - 6 into 10 to the power of 23.
Thus, a 1 M solution of glucose contains the same number of solute molecules per litre,
as a 1 M solution of urea or any other substance.
The concentration of solutes dissolved in body fluids are much less than 1 M.
Many have concentrations in the range of milimoles per litre, or .001 M.
Others have concentrations in the range of micromoles per litre, or .000001 M.
Some are concentrations of nanomoles per litre, or .000000001 M.
Hydrogen Ions and Acidity.
The hydrogen ion H+ formed by the loss of the electron, is thus a single free proton.
Hydrogen ions are formed when the proton of a hydrogen atom in a molecule,
is released from the molecule, leaving behind its electron.
Molecules that give rise to hydrogen ions are called acids.
For example:
Hydrochloric acid - HCL --> H+ + CL- (Chloride)
Carbonic acid - —> H+ + HCO3 - (Bicarbonate)
Lactic acid - CH3 - CH2O - COOH —> H+ + CH3 - CH2O - COO- (Lactate)
Conversely, any substance that can accept a hydrogen ion is termed as a base.
Bicarbonate and Lactate are bases since they can combine with the hydrogen ions.
These bases will remove hydrogen ions from solution, lowering the hydrogen ion concentration.
Hydrogen ion concentration refers to the hydrogen ions that are free in solution,
and not those that maybe bound in lactic acid or to amino groups to form R - NH3+.
When hydrochloric acid is dissolved in water, 100% of its atoms separate to form,
hydrogen and chloride ions, which do not recombine in solution.
In the case of lactic acid, however,
only a fraction of the total number of lactic acid molecules in solution,
release hydrogen ions at any instant.
Therefore if a 1M solution of hydrochloric acid is compared with a 1M solution of lactic acid,
the hydrogen ion concentration will be lower in the lactic acid solution,
than in the hydrochloric acid solution.
Hydrochloric acid and other acids that are 100% organised in solutions are known as strong acids,
while carbonic and lactic acid, which do not completely ionise in solution, are weak acids.
The same principle applies to the definition of strong and weak bases.
Strong bases are 100% ionised in solution while weak bases are only partly ionised.
The acidity of a solution refers to the free or unbound hydrogen ion concentration in the solution.
Higher the hydrogen ion concentration , the greater the acidity.
The hydrogen ion concentration is frequently expressed in terms of pH of a solution,
which is defined of the negative logarithm to the base 10, of the hydrogen ion concentration.
Thus the solution with a hydrogen concentration of 10 to the power of minus 7 M has a pH of 7.
A more acidic solution with the concentration of 10 power minus 6 M has a pH of 6.
As the acidity increases.the pH decreases.
A change in pH from 7 to 6 represents a 10 fold increase in hydrogen ion concentration.
Pure water has a hydrogen ion concentration of 10 to the power of minus 7 M, or pH of 7.0,
and is a neutral solution.
Alkaline solutions have a lower hydrogen ion concentration, or pH greater than 7.
Those with a higher hydrogen ion concentration are acidic solutions.
The body’s extra cellular fluid has a hydrogen concentration,
of about 4 into 10 to the power of minus 8 M or a pH of about 7.4, which is slightly alkaline.
Intercellular fluids have a slightly higher hydrogen ion concentration than extra cellular fluid.
The ionisation of carboxyl and amino groups in various molecules in the body,
involves the release and uptake, respectively of hydrogen ions.
These groups behave as weak acids and bases.
Increasing the hydrogen ion concentration decreases the number of carboxyl groups,
since it increases the probability that an ionised carboxyl group,
will bump into a hydrogen ion and combine with it.
R - COO - + H+ —> R - COOH.
Lowering the hydrogen ion concentration has the opposite effect.
Thus changes in the acidity of solutions containing molecules with carboxyl groups and amino groups,
will alter the net electric charge of these molecules by shifting the ionisation reaction to the right or left.
If the electric charge of a molecule is altered, its interaction with the other molecules.
or with other regions with in the same molecule is altered.
In the extra cellular fluid hydrogen ion concentration beyond the ten fold pH range of 7.8 to 6.8,
are incompatible with human life if maintained for more than a brief period of time.
Even small changes in the hydrogen ion concentration can produce large changes in the activity of cells.
Classes of organic molecules.
Because most naturally occurring carbon containing molecules are found in living organisms,
a study of these compounds became known as organic chemistry.
Inorganic chemistry is the study of non carbon containing molecules.
However, the chemistry of living organisms, biochemistry,
now forms only a portion of the broad field of organic chemistry.
One of the properties of the carbon atom that makes life possible ,
is its ability to form 4 covalent bonds with other atoms, in particular with other carbon atoms.
Since carbon atoms can also combine with hydrogen, oxygen, nitrogen and sulphur atoms,
a vast number of compounds can be formed with a relatively few chemical elements.
Some of these molecules are extremely large macromolecules, being composed of thousands of atoms.
Such large molecules are formed by linking together hundreds of smaller molecules, or subunits,
and are known as polymers, which means many small parts.
The structure of macromolecules depends on the structure of the subunits linked together,
and the position along the chain of each type of subunit.
Most of the different types of organic molecules in the body, can be classified into one of four groups.
Carbohydrates.
Lipids.
Proteins.
Nucleic acids.
Carbohydrates.
Although carbohydrates account for only 3% of the body’s organic matter,
they play a central role in the chemical reactions that provide cells with energy.
Carbohydrates are composed of mainly carbon, hydrogen and oxygen atoms,
with the proportions represented by the general formula -
Cn(H2O)n, where n is any whole number.
It is from this formula that the class of molecules gets its name,
carbohydrate - water containing carbon atoms.
Linked to most of the carbon atoms in a carbohydrate are a hydrogen atom and a hydroxyl group.
Chemical groups containing nitrogen and phosphorus atoms,
may also be linked to the basic carbohydrate structure.
The presence of numerous hydroxyl groups, which are polar,
makes carbohydrates readily soluble in water.
Most carbohydrates taste sweet, and it is among the carbohydrates,
that we find the substances known as sugars.
The simplest sugars are monosaccharides, the most abundant of which is glucose.
There are two ways of representing the structure of monosaccharides.
The first is a conventional representation of organic molecules into two dimensions.
The second gives a better representation of the three dimensional shape of monosaccharides.
Five carbon atoms and one oxygen atom form a ring that lies essentially in a flat plain.
The hydrogen and hydroxyl groups are each carbon lying above and below the plane of this ring.
If one of the hydroxyl groups below the ring is shifted to a position above the ring,
a different monosaccharide is produced.
Most monosaccharide in the body contain 5 or 6 carbon atoms,
and are called pentoses and hexoses respectively.
Larger carbohydrate molecules can be formed by linking a number of monosaccharides together.
Carbohydrate molecule composed of two monosaccharides are known as disaccharides.
Sucrose, table sugar, is composed of two monosaccharides, glucose (a hexose) and fructose(a pentose).
The linking together of most monosaccharides involves the removal of a hydroxyl group,
from one monosaccharide, and a hydrogen atom from the other, giving rise to a molecule of water,
and linking the two sugars together through a oxygen atom.
Conversely, hydrolysis of the disaccharide breaks this linkage,
by adding back the water and thus uncoupling the two monosaccharides.
Additional disaccharide are maltose (glucose-glucose) formed during the digestion,
of large carbohydrate molecules in the intestinal tract ,
and lactose (glucose-galactose) present in breast milk.
When monosaccharides are linked together to form large polymers,
the molecules are known as polysaccharides.
Starch found in plant cells, and glycogen present in animal cells are examples of polysaccharides.
Both of these polysaccharides are composed of thousands of glucose molecules,
linked together in long chains.
They differ only in the degree of branching along the chain.
Hydrolysis of these polysaccharides leads to the release of glucose subunits.
Lipids.
Lipids are molecules composed predominately of hydrogen and carbon atoms.
Since these atoms are linked by neutral covalent bonds, lipids are non-polar molecules,
and thus insoluble in water.
It is the insolubility in water that characterises this class of organic molecules.
The lipids, which account for 40% of the bodies organic matter,
can be divided into three major subclasses:
Triglycerides, phospholipids, and steroids.
Triglycerides and fatty acids.
Triglycerides constitute the majority of the body’s lipids.
It is these molecules that are generally referred to as fat.
Triglycerides are formed by linking together of glycerol and fatty acids.
Glycerol is a three carbon carbohydrate CH2(OH)CH(OH)CH2(OH).
Each hydroxyl group in glycerol is linked to the carboxyl group of a fatty acid,
to form a triglyceride molecule.
Because fatty acids are synthesised in the body by linking together of two carbon fragments,
most fatty acids have a even number of carbon atoms.
16 and 18 carbon fatty acids are the most common.
When all the carbons in a fatty acid chain are linked by single covalent bonds,
the fatty acid is said to be a saturated fatty acid.
Some fatty acids contained one or more double bonds between carbon atoms,
and these are known as unsaturated fatty acids.
If more than one double bond is present, the fatty acid is said to be polyunsaturated.
Animal fat generally contain a high proportion of saturated fatty acids.
Vegetable fats contain more polyunsaturated fatty acids.
The three fatty acids in a molecule of triglyceride need not be identical.
Therefore, a variety of fats can be formed with fatty acids of different chain lengths,
and degree of saturation.
Hydrolysis of triglycerides releases the fatty acids from glycerol,
and these products can be utilised to provide energy for cell functions.
Some fatty acids can be altered to produce a special class of molecules,
that regulate a number of cell functions.
These modified fatty acids are collectively termed as eicosanoids.
They are derived from 20 carbons, polyunsaturated fatty acid arachidonic acid.
Phospholipids.
The phospholipids are similar in over all structure to triglycerides, with one important difference.
The third hydroxyl of glycerol, rather than being attached to a molecule of fatty acid,
is linked to a phosphate.
In addition, a small polar or ionised nitrogen containing molecule is usually attached to this phosphate.
These groups constitute a polar region at one end of the phospholipid molecule,
while fatty acid change provide a non-polar region at the opposite end.
Therefore phospholipids are amphipathic.
In water they get organised into clusters, with the polar ends being attracted to the water molecules.
Steroids.
Steroids have a distinctly different structure from that of the other two subclasses of lipid molecules.
Four interconnected rings of carbon atoms form the skeleton of all steroids.
A few polar hydroxyl groups may be attached to this ring structure,
but they are not numerous enough to make a steroid water soluble.
Examples of steroids are cholesterol, cortisol from the adrenal glands,
and female (estrogen) and male (testosterone) sex hormones secreted by the gonads.
Proteins.
The term protein comes from the Greek proteios, which means ‘of the first rank’,
which aptly describes their importance.
These molecules which account for 50% of the organic material in the body,
play critical roles in almost every physiological process.
Proteins are composed of carbon, hydrogen, oxygen, nitrogen and small amounts of other elements,
notably sulphur.
They are macro molecules, often containing thousands of atoms, and like most large molecules,
are formed by linking together a large number of small subunits to form long chains.
The subunits of protein structure is an amino acid.
Thus, proteins are polymers of amino acids.
Every amino acid, expect one, proline, has an amino acid (-NH2) and the carboxyl (COOH) group,
linked to the terminal carbon atom in the molecule.
The third bond of this terminal carbon atom is linked to a hydrogen atom,
and the fourth to the remainder of the molecule, which is known as amino acid side chain.
The proteins of all living organisms, including human beings,
are composed of the same set of 20 different amino acids, corresponding to the 20 different side chains.
The side chains may be non polar (8 amino acids), polar (7 amino acids), or ionised (5 amino acids).
Polypeptides.
Amino acids are linked together in chains by a reaction between the carboxyl group of one amino acid,
and the amino group of the next amino acid in sequence.
In the process, a molecule of water is formed.
The bond formed between the amino and carboxyl group is called a peptide bond,
and it is like polar covalent bond.
When two amino acids are linked together, one end of the resulting molecule has a free amino group,
and the other end has a free carboxyl group.
Additional amino acid can be linked by peptide bonds to both ends of this chain.
A sequence of amino acids linked by peptide bonds is known as polypeptide.
The peptide bonds form the backbone of the polypeptide,
and the remainder of each amino acid stick’s out to the side of the chain.
If the number of amino acid in a polypeptide is less than 50, the molecule is known as a peptide.
If the sequence is more than 50 units long, the polypeptide is known as a protein.
The number 50 is arbitrary, but has become the convention for distinguishing,
between large and small polypeptide chains.
After certain proteins have been synthesised,
one or more monosaccharides are covalently attached to the side chains of specific amino acids,
(serine and threonine) to form a class of proteins called glycoproteins.
Primary protein structure.
There are only two variables that determine the primary structure of a protein or peptide:
1. The total number of amino acids in the chain.
2. The specific type of amino acid at each position along the chain.
Each position can be occupied by one of the twenty different amino acids.
Let us consider the number of different peptides that can be formed with only three amino acids.
Any one of the 20 different amino acids may occupy the first position in the sequence.
Any one of the 20 may occupy the second position.
Any one of the 20 may occupy the third position.
This results in a 20 into 20 into 20 equal to 8000 possible sequences of 3 amino acids.
If the peptide is 6 amino acids in length,
20 to the power of 6 = 64,000,000 possible combinations can be found.
Peptides that are only 6 amino acids long are still very small molecules compared to proteins,
which may have sequences of 1,000 or more amino acids.
Thus when 20 different amino acids an almost unlimited variety of polypeptides,
can be formed by altering both the amino acid sequence,
and the total number of amino acids in the chain.
Protein conformation.
The structure of a polypeptide is analogous to the string of beads,
each bead representing a single amino acid.
Moreover, since amino acids can rotate around their peptide bonds,
a polypeptide chain is flexible and can be bent into a number of shapes,
just as a string of beads can be twisted into many configurations.
The three dimensional shape of a molecule is known as its conformation.
The conformations of peptides and proteins play a major role in the functioning of these molecules.
Four factors determine the conformation of a polypeptide chain,
once the amino acid sequence has been formed.
1. Attractions between polar and ionised regions along the polypeptide chain.
2. Weak forces of attraction between non polar regions in close proximity to each other,
and known as van der Waals forces.
3. Attractions between the chain and surrounding water molecules.
4. Covalent bonds linking the side chains of two amino acids.
An example of the attractions between various regions along the polypeptide chain,
is the hydrogen bondings that can occur between the hydrogen linked to the nitrogen atom,
in one peptide bond, and the double bonded oxygen in another peptide bond.
Since the peptide bonds occur at regular intervals along a polypeptide chain,
the hydrogen bonds between them tend to force the polypeptide chain into a helical configuration,
known as a alpha helix.
However, for several reasons, a given region of a polypeptide chain may not assume a helical shape.
The sizes of the side chain interactions in the region can interfere with the coiling and distort the helix,
producing shapes with no regularity.
These non helical regions are known as random coil configurations and occur in regions,
where the polypeptide is bent.
Water plays an important role in determining the conformation of a polypeptide chain.
When polypeptides are dissolved in water, the polarised and ionised regions,
are attracted to the surrounding polar water molecules.
This tends to force the polar and ionised side chains towards the surface of the molecule,
orienting them towards the water.
When these hydrophobic chains are close to each other, they are attracted by van der Waals forces,
due to the weak electromagnetic fields that surrounds electrically neutral atoms.
The fourth factor influencing the conformation of a polypeptide chain,
is the covalent bonding that can occur between certain amino acids side chains.
The side chain of the amino acid cysteine contains a sulfhydryl group (R—SH),
which can react with the sulfhydryl group, in another cysteine side chain,
to produce a covalent disulfide bond (R-S-S-R), linking the two amino acid side chains together.
Disulfide bonds form strong links between portions of a polypeptide chain,
in contrast to the weaker hydrogen and ionic bonds, which are more easily broken.
These same bonds are also involved in other intermolecular interactions.
The number of proteins contain more than one polypeptide chains.
The same factors that influence the conformation of a single polypeptide chain,
also determine the interaction between the polypeptide chain, in a multi chain protein.
Thus, the separate chains can be held together by interactions between various polar,
ionised and non polar side chains, as well as by disulfide bonds between the chains.
The primary structures of a large number of proteins are known,
but three dimensional conformations have been determined for only some of them.
Because of the multiple factors that can influence the folding of a polypeptide chain,
it is not yet possible to predict accurately the confirmation of a protein,
from its primary amino acid sequence.
Nucleic acids.
Nucleic acids account for only 2% of the body’s weight,
yet it is these molecules that ultimately determine the properties of all cells.
Nucleic acids are responsible for the storage, expression, and transmission of genetic information.
It is the expression of genetic information that determines whether one is a human being or a mouse,
or whether a cell is a muscle cell, or a nerve cell.
There are two classes of nucleic acids, deoxyribonucleic acid, DNA, and ribonucleic acid, RNA.
DNA molecules store genetic information coded in terms of their repeating sub unit structure.
RNA molecules are involved in the decoding of this information into instructions,
for linking together a specific series of amino acids, to form a specific protein.
Both types of nucleic acid are polymers composed of liner sequences of repeating subunits.
Each subunit, known as a nucleotide, has three components: a phosphate group, a sugar,
and a ring of carbon and nitrogen atoms, often refer to as a base, because it can accept hydrogen ions.
The phosphate group of one nucleotide is linked to the sugar of the adjacent nucleotide,
to form a chain of nucleotides, with the base sticking out to the side of the phosphate-sugar backbone.
DNA.
The nucleotides in DNA contain the sugar deoxyribose - hence, the name deoxyribonucleic acid.
Four different nucleotides are present in DNA,
corresponding to four different bases that can be linked to deoxyribose.
The four nucleotide bases are divided into two classes:
1. The purine bases, adenine and guanine, which have double fused rings of nitrogen and carbon atoms.
2. The pyrimidine bases, cytosine and thymine have only a single ring.
A DNA molecule consists of not one but two chains of nucleotides coiled around each other,
in the form of a double helix.
The two chains are held together by hydrogen bombs between purine and pyrimidine bases.
This paring between purine and pyrimidine bases maintains a constant distance,
between the sugar-phosphate backbones of the two chains as they coil around each other.
Specificity is imposed on the base parings by the location of the hydrogen bonding groups,
in the four bases.
Three hydrogen bonds are formed in the purine guanine and pyrimidine cytosine (G-C pairing).
Only two hydrogen bonds can be formed between the purine adenine,
and pyrimidine thymine (A-T Pairing).
As a result G always pairs with C, and A with T.
Specificity in base pairing provides the mechanism for duplicating and transferring genetic information.
RNA.
The structure of RNA molecules, differs in only a few respects from that of DNA.
1. RNA molecules consists of a single, (rather than a double) chain of nucleotides.
2. In RNA the sugar in each nucleotide is ribose rather than deoxyribose in DNA.
3. The pyrimidine base thymine in DNA is replaced in RNA by the pyrimidine base uracil,
which can base pair with adenine (A-U pairing).
The other three bases, adenine, guanine and cytosine, are the same both in RNA and DNA.
Although RNA contains only a single chain of nucleotides, portions of this chain can bend back on itself,
and base pair with other nucleotides in the same chain.