FEATURES OF AMINO ACIDS AND PEPTIDES IN BIOCHEMISTRY

AMINO ACIDS

Amino acids are organic compound containing amine (-NH₂) and carboxyl (-COOH) functional groups, along with a side chain (R group) specific to each amino acid. The key elements of an amino acid are carbon (C), hydrogen (H), oxygen (O), and nitrogen (N), although other elements are found in the side chains of certain amino acids.

Or, Amino acid is an organic acid in which one or more hydrogen atoms are replaced by an amino group. Thus, it contains at least a free amino group and a carboxyl group.

Nomenclature of amino acids: About thirty amino acids have been obtained from the hydrolysis of proteins, and twenty of these are relatively common. The names, structures, and three-letter abbreviations of the common amino acids are given in the table. Notice that all the amino acids have trivial names, even those for which the systematic names would not be cumbersome.

Essential	Nonessential
Valine	Proline
Leucine	Cystine
Isoleucine	Aspartic acid
Phenylalanine	Serine
Threonine	Alanine
Lysine	Glycine
Arginine	Tyrosine

The properties of amino acid

v They are amphoteric in reaction.

v They have no color, crystalline substances.

v Although they are soluble in water but insoluble in ether or benzene.

v They are optically active, except glycine.( Glycine has no asymmetric carbon atom in its structure and hence is optically inactive)

v Depending on the pH, they may have no net charge or may have either a positive or a negative charge (ionic properties).

The function of amino acids:

·        Act as the building of protein

·        Act as precursors of the hormone, purines, pyrimidines, and vitamins, like pantothenic and folic acid.

·        Certain amino acids appear to be involved in the transmission of impulses in the nervous system.

·        Essential amino acids support growth in infants and maintain health in adults.

Classification of amino acids:

1.according to their functional groups.

·        Monoamino monocarboxylic acid

·        Monoamino dicarboxylic acid

·        Diamino monocarboxylic

·        Imino acids

2.according to their biological value.

·        Essential amino acids

·        Non essential amino acids

3.according to the nature of their metabolic and products.

·        Ketogenic amino acids

·        Glucogenic amino acids

·        Both ketogenic and glucogenic amino acids

4.according to the polarity of their side chains (R group)

·        Nonpolar amino acids

Optical activity of  amino acids: glycine does not have an asymmetric carbon atom and, therefore, does not have optical isomers. Alanine and all other amino acids have an asymmetric carbon at position 2, the alpha- carbon atom. for this reason, they are all optically active and exist in D and L forms which are nonsuperimposible mirror-image isomers. If the carbon group is written at the top, the D-form refers to the isomer with the –NH3 group on the right, the L form is the isomer with the  -NH3 group on the left. e.g., glyceraldehydes.

Ø   synthesis of amino acids

• Strecker synthesis
• starting material: R-aldehyde
• reagents: cyanide (KCN), ammonium (NH4Cl)
• product: amino acid with the -R group originally on the aldehyde
• Gabriel synthesis
• starting material: R-halide
• reagents: 1. phthalimide, 2. NH2-NH2
• product: amino acid with the -R group originally on the halide

Essential and non-essential amino acid

Essential amino acid	Non-essential amino acid
Valine	Glycine
Leucine	Alanine
Isoleucine	Tyrosine
Phenylalanine	Serine
Tryptophan	Proline
Threonine	Hydroxyproline
Methionine	Cysteine
Lysine	Cystine
Arginine	Aspartic acid
Histidine	Glutamic acid

An essential amino acid, or indispensable amino acid is an amino acid that cannot be synthesized de novo (from scratch) by the organism, and thus must be supplied in its diet. The nine amino acids humans cannot synthesize are phenylalanine, valine, threonine, tryptophan, methionine, leucine, isoleucine, lysine, and histidine (i.e., F V T W M L I K H).

Six other amino acids are considered conditionally essential in the human diet, meaning their synthesis can be limited under special pathophysiological conditions, such as prematurity in the infant or individuals in severe catabolic distress. These six are arginine, cysteine, glycine, glutamine, proline, and tyrosine (i.e., R C G Q P Y). Five amino acids are dispensable in humans, meaning they can be synthesized in sufficient quantities in the body. These five are alanine, aspartic acid, asparagine, glutamic acid and serine (i.e., A D N E S).

Interchangeability

The distinction between essential and non-essential amino acids is somewhat unclear, as some amino acids can be produced from others. The sulfur-containing amino acids, methionine, and homocysteine, can be converted into each other but neither can be synthesized de novo in humans. Likewise, cysteine can be made from homocysteine but cannot be synthesized on its own. So, for convenience, sulfur-containing amino acids are sometimes considered a single pool of nutritionally equivalent amino acids as are the aromatic amino acid pair, phenylalanine, and tyrosine. Likewise, arginine, ornithine, and citrulline, which are interconvertible by the urea cycle, are considered a single group.

Non-Essential Amino Acids

The another type is the non-essential amino acid, 11 of which exists and is synthesized by the body. Thus, although they are an important part of building proteins, they do not need to be included in an everyday diet. Eight of these non-essential acids are also known as “conditional,” meaning that the body may not be capable of producing enough of them when presented with substantial stress or illness.

The sources of amino acids in the blood (body):

                               I.            Tissue protein breakdown

                             II.            Dietary proteins

                          III.            Intracellular synthesis

Importance of amino acids: Amino acids are at the basis of all life processes, as they are absolutely essential for every metabolic process.

The majority of health issues such as obesity, high cholesterol levels, diabetes, insomnia, erectile dysfunction or arthritis can essentially be traced back to metabolic disturbances. This also applies to hair loss and serious cases of wrinkle formation.

This is why it is important to act sooner rather than later to ensure that the essential amino acids are available to the body in sufficient quantities.

Unfortunately this cannot be guaranteed nowadays, due to the poor quality of our diet. This is why supplementation with amino acids is recommended.

Peptide: The covalent chemical bonds are formed when the carboxyl group of one amino acid reacts with the amino group of another. The shortest peptides are dipeptides, consisting of 2 amino acids joined by a single peptide bond, followed by tripeptides, tetrapeptides, etc. A polypeptide is a long, continuous, and unbranched peptide chain. Hence, peptides fall under the broad chemical classes of biological oligomers and polymers, alongside nucleic acids, oligosaccharides, and polysaccharides, etc.

Nomenclature of peptides: Peptides are named by listing the amino acids present in the order they occur starting from the N-terminal amino acid. The  typical amino acid suffix ’-ine’ is replaced by the suffix ‘-yl’ for all amino acids except the C-terminal amino acids

Peptide names formed in this way are not used very often. Instead, the standard three-letter abbreviations are used. For example, glycylalanyl phenylalanine may be represented as Gly-Ala-Phe.

Peptide bond: A peptide bond, also known as an amide bond, is a covalent chemical bond linking two consecutive amino acid monomers along a peptide or protein chain.

Formation: It is formed by reactions (e.g., removal of one mole of water) between the alpha-amino group of one amino acid and the alpha-carboxyl group of another amino acid given rise peptide link (-CO-NH-). This is shown below

Characteristics:

o   The C-N bond in the peptide bond has partial double bond properties that make it rigid and prevent the adjacent groups from rotating freely.

o   Neither the C=O nor the N-H in the peptide bond can dissociate.

Importance: It is the peptide bond that holds various amino acids together in a specific sequence and number.

Synthesis: When two amino acids form a dipeptide through a peptide bond it is called condensation. In condensation, two amino acids approach each other, with the acid moiety of one coming near the amino moiety of the other. One loses hydrogen and oxygen from its carboxyl group (COOH) and the other loses hydrogen from its amino group (NH₂). This reaction produces a molecule of water (H₂O) and two amino acids joined by a peptide bond (-CO-NH-). The two joined amino acids are called a dipeptide.

The amide bond is synthesized when the carboxyl group of one amino acid molecule reacts with the amino group of the other amino acid molecule, causing the release of a molecule of water (H₂O), hence the process is a dehydration synthesis reaction (also known as a condensation reaction).

The formation of the peptide bond consumes energy, which, in living systems, is derived from ATP. Polypeptides and proteins are chains of amino acids held together by peptide bonds. Living organisms employ enzymes to produce polypeptides, and ribosomes to produce proteins. Peptides are synthesized by specific enzymes. For example, the tripeptide glutathione is synthesized in two steps from free amino acids, by two enzymes: gamma-glutamylcysteine synthetase and glutathione synthetase.

Polypeptides: chains containing more than ten but fewer than a hundred amino acid residues are called polypeptides.

Degradation: A peptide bond can be broken by hydrolysis (the addition of water). In the presence of water, they will break down and release 8–16 kilojoule/mol (2–4 kcal/mol)  of free energy. This process is extremely slow, with the half-life at 25C of between 350 and 600 years per bond

In living organisms, the process is normally catalyzed by enzymes known as peptidases or proteases, although there are reports of peptide bond hydrolysis caused by conformational strain as the peptide/protein folds into the native structure. This the non-enzymatic process is thus not accelerated by transition state stabilization, but rather by ground-state destabilization.

Peptide classes

Peptides are divided into several classes, depending on how they are produced:

Milk peptides 

Two naturally occurring milk peptides are formed from the milk protein casein when digestive enzymes break this down; they can also arise from the proteinases formed by lactobacilli during the fermentation of milk.

Ribosomal peptides 

Ribosomal peptides are synthesized by the translation of mRNA. They are often subjected to proteolysis to generate the mature form. These function, typically in higher organisms, as hormones and signaling molecules. Some organisms produce peptides as antibiotics, such as microcins. Since they are translated, the amino acid residues involved are restricted to those utilized by the ribosome.

However, these peptides frequently have posttranslational modifications such as phosphorylation, hydroxylation, sulfonation, palmitoylation, glycosylation and disulfide formation. In general, they are linear, although lariat structures have been observed. More exotic manipulations do occur, such as racemization of L-amino acids to D-amino acids in platypus venom.

Nonribosomal peptides 

Nonribosomal peptides are assembled by enzymes that are specific to each peptide, rather than by the ribosome. The most common non-ribosomal peptide is glutathione, which is a component of the antioxidant defenses of most aerobic organisms. Other nonribosomal peptides are most common in unicellular organisms, plants, and fungi and are synthesized by modular enzyme complexes called nonribosomal peptide synthetases.

These complexes are often laid out in a similar fashion, and they can contain many different modules to perform a diverse set of chemical manipulations on the developing product. These peptides are often cyclic and can have highly complex cyclic structures, although linear nonribosomal peptides are also common. Since the system is closely related to the machinery for building fatty acids and polyketides, hybrid compounds are often found. The presence of oxazoles or thiazoles often indicates that the compound was synthesized in this fashion.

Peptide fragments Peptide fragments refer to fragments of proteins that are used to identify or quantify the source protein. Often these are the products of enzymatic degradation performed in the laboratory on a controlled sample, but can also be forensic or paleontological samples that have been degraded by natural effects.

Peptides in molecular biology

Peptides received prominence in molecular biology for several reasons. The first is that peptides allow the creation of peptide antibodies in animals without the need of purifying the protein of interest. This involves synthesizing antigenic peptides of sections of the protein of interest. These will then be used to make antibodies in a rabbit or mouse against the protein.

Another reason is that peptides have become instrumental in mass spectrometry, allowing the identification of proteins of interest based on peptide masses and sequence.

Peptides have recently been used in the study of protein structure and function. For example, synthetic peptides can be used as probes to see where protein-peptide interactions occur- see the page on Protein tags.

Inhibitory peptides are also used in clinical research to examine the effects of peptides on the inhibition of cancer proteins and other diseases. For example, one of the most promising applications is through peptides that target LHRH.These particular peptides act as an agonist, meaning that they bind to a cell in a way that regulates LHRH receptors. The process of inhibiting the cell receptors suggests that peptides could be beneficial in treating prostate cancer. However, additional investigations and experiments are required before the cancer-fighting attributes, exhibited by peptides, can be considered definitive.

Conclusion: A large proportion of our cells, muscles, and tissue is made up of amino acids, meaning they carry out many important bodily functions, such as giving cells their structure. They also play a key role in the transport and the storage of nutrients. Amino acids have an influence on the function of organs, glands, tendons, and arteries.

Reference: 

(1)https://biology.tutorvista.com/biomolecules/proteins.html?view=simple

(2)https://en.m.wikipedia.org/wiki/aminoacid 

(3)"A Guide to Biochemistry" By Dr.Agarwala

(4) https://en.m.wikipedia.org/wiki/peptide