L4_Aminoacids, peptides, proteins (2)

α-Aminoacids.
α-Aminoacids – class of organic compounds, which may be considered
as derivatives of carboxylic acids, in which hydrogen atom in position
2 substituted by amino group.
Almost all α-aminoacids, except glycine (2-aminopropanoic acid)
contain asymmetric carbon, it means that optical isomerism is typical
for mentioned class of compounds.

Classification
By the one to which the carbon atom is attached an amino- (or imino-) group, the amino acids are divided into:
α-amino acids (carboxyl and amino groups are attached to the same carbon atom);
β-amino acids (the amino group is attached to a carbon atom adjacent to that to which the carboxyl is attached),
γ-amino acids (amino group attached through one carbon atom from a carboxylic acid), etc.

Proteinogenic aliphatic α-amino acids.

Proteinogenic aliphatic α-amino acids.

Proteinogenic aliphatic α-amino acids.

Proteinogenic aromatic α-amino acids.

Proteinogenic heterocyclic α-amino acids.

Neutral hydrophobic amino acids

Neutral hydrophobic amino acids

Neutral hydrophilic amino acids

Neutral hydrophilic amino acids

Amino acids having an alkaline reaction of the solution

Amino acids having an acid reaction of the solution

Non-essential AA: alanine, aspartic acid, asparagine, glutamic acid, glutamine, proline, glycine, serine.
Enzyme systems of the human body are able to synthesize AA from other intermediate in sufficient quantity.
Essential AA: valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine.
Enzyme systems of the human body are not synthesized.
Partially essential AA: arginine, histidine.
Synthesized in the body in insufficient quantities.
The human body depends on the constant intake of these 10 AA in the food proteins - in the absence of even one of the essential amino acids, protein synthesis stops.

Essential α-aminoacids.

Nomenclature
1. Amino acids are referred to as carboxylic acids, indicating the position of the amino group.
2. The positions of the amino group and other substituents in the main chain are indicated by letters or numbers in order of precedence.

Optical isomerism
These isomers rotate the plane of polarization of light passing through their solution.
The composition of proteins consists of almost only L-isomers.
α-amino acid
L-α- amino acid
D-α- amino acid

Physical properties
Amino acids - colorless crystalline substances with high melting temperatures.
Melting is accompanied by a decomposition of substance.
In water, amino acids dissolve well.
Aqueous solutions of single-base amino acids almost always have a nearly neutral reaction.

Preparation of α-aminocarboxylic acids.
2. Aminolysis α-halogencarboxylic acids
1. Isolation from native sources.

3. Strecker method
Preparation of α-aminocarboxylic acids.

Chemical properties of α-aminocarboxylic acids.
Formation of intramolecular salts
pH of aqueous solutions ≈ 7

Chemical properties of α-aminocarboxylic acids.
Formation of salts.

1. Alkylation
2. Acylation
Chemical properties of α-aminocarboxylic acids.
Properties of amino-group.

3. Reaction with nitrous acid.
Chemical properties of α-aminocarboxylic acids.
Properties of amino-group.

1.Formation of esters.
2. Formation of halogenanhydrides.
Chemical properties of α-aminocarboxylic acids.
Properties of carboxylic groups.

3. Formation of amides.
Chemical properties of α-aminocarboxylic acids.
Properties of carboxylic groups.

1. Intramolecular dehydration.
2. Reaction with ninhydrin.
Chemical properties of α-aminocarboxylic acids.
Specific properties.

3. Transamination
4. Reaction with с 2,4-dinitrofluorobenzene (Sanger reactive)
Chemical properties of α-aminocarboxylic acids.
Specific properties.

5. Reaction with phenylisothiocyanate (Edman reaction)
Chemical properties of α-aminocarboxylic acids.
Specific properties.

6. Formation of complex compound
7. Decarboxylation
Chemical properties of α-aminocarboxylic acids.
Specific properties.

Biologically active compounds – derivatives of α-aminoacids.
histidine
histamine
tryptophan
serotonin
thyroxine
tyrosine

Decarboxylation of histidine
Histamine
H1 receptors are coupled with phosphatidyl inositol messenger system.
H2 receptors are coupled with adenylyl cyclase messenger system.
Histaminergic neurones of CNS, gastric mucosa cells, basophils, mast cells are the chief source of histamine.

Functions of histamine:
contraction of smooth muscles of gastro-intestinal tract, bronchi;
it increases HCl secretion in stomach;
it shows vasodilatory effect;
it increases vasopermeability;
it is the inflammatory process mediator;
it is the allergic reaction mediator;
it is the central nervous system mediator as well.

Decarboxylation of tryptophan and its derivatives (5-hydroxytryptophan)
Functions of serotonin
- mediator of CNS;
- potent vasoconstrictor;
- stimulator of smooth muscle contraction (of bronchi, uterus, intestine);
- mediator of inflammation;
- participates in regulation of body temperature, breathing, renal filtration;
- modulate the process of blood clotting.

Decarboxylation of tyrosine
tyrosinase
melanine

Functions of epinephrine:
- “fight or flight”
-to increase cardiac output and to raise glucose levels in the blood.
-to increase the level of circulating free fatty acids.
-constriction in many networks of minute blood vessels but dilates the blood vessels in the skeletal muscles and the liver.

Peptides.
Peptides – polyamides formed by α-aminoacids.

Synthesis of peptides.
Possible products of interaction between two α-aminoacids.
Alanine
Glycine
Ala-Ala
Ala-Gly
Gly-Gly
Gly-Ala

Synthesis of peptides.

Synthesis of peptides.

The main steps outlined in the synthesis of dipeptide from glycine and alanine.
1. Protection of NH2 groups:
Protection and аctivation of the -CООН group:

2. Formation of a dipeptide:

3. Deletion of protection groups (removal of protection):
The above sequence of reactions can be repeated with other amino acids further down to the formation of a tripeptide, a tetrapeptide, etc.

Proteins.
Proteins – macromolecular compounds, polypeptides with molecular weigh more than10000.
Primary structure – caused by amino acids sequence.
Secondary structure - regularly repeating local structures stabilized
by hydrogen bonds.
Tertiary structure - the spatial relationship of the secondary
structures to one another.
Quaternary structure - the structure formed by several protein
molecules bonded by non-covalent bonds.

The structure of the protein molecule
Primary
Secondary
Tertiary
Quaternary

Primary protein structure
The sequence of amino acid residues in the polypeptide chain linked peptide bonds.

The mechanism of peptide bond formation

Turn - 3.6 amino acid residues
Step - 0.544 nm.
-CO-
-NH-
Secondary protein structure
rolled into a spiral polypeptide chain.
It is kept in space due to the formation of hydrogen bonds between the groups -CO- and -NH-, located on the neighboring spiral circles.

Secondary structure
alpha-helix pleated sheet

Tertiary structure
The real three-dimensional configuration of a twisted spiral in the space of a polypeptide chain (that is, a spiral swirled into a spiral).
Supported by bonds between functional groups of radicals.
Disulfide bridges (-S-S-) between sulfur atoms.
Ester bridges between carboxylic (-COOH) and hydroxyl groups (-OH).
Salt bridges between the carboxyl group (-COOH) and the amino group (-NH2).

Quaternary protein structure
Form of interaction between multiple polypeptide chains.
Among themselves, polypeptide chains are connected by hydrogen, ionic, hydrophobic and other bonds.
The hemoglobin molecule is constructed from four polypeptide chains (Mr = 17000 each). When coupled with oxygen, the molecule changes its quaternary structure, capturing oxygen.
It is the spatial structure that determines the chemical and biological properties of proteins