AMINO ACIDS and their chemistry




The proteins speak: “We are the basis of structure and function of life; Composed of twenty amino acids, the building blocks; Organized into primary, secondary, tertiary and quaternary structure; Classified as simple, conjugated and derived proteins.”

Proteins are the most abundant organic molecules of the living system. They occur in every part of the cell and constitute about 50% of the cellular dry weight. Proteins form the fundamental basis of structure and function of life. Amino acids are the building block of proteins.

The term amino acid refers to a molecule containing an amino group and a carboxyl group. Although there can be different isomers of the amino acid usually refer to alpha-amino acid. These amino acids contain the amino group on the alpha carbon. If the amino acids contain the amino group on the beta carbon then it is called as beta amino acid.

STANDARD AMINO ACIDS

As many as 300 amino acids occur in nature— of these, only 20—known as standard amino acids are repeatedly found in the structure of proteins, isolated from different forms of life animal, plant and microbial.

General structure of amino acids

The amino acids are termed alpha-amino acids, if both the carboxyl and amino groups are attached to the same carbon atom. The α-carbon atom binds to a side chain represented by R which is different for each of the 20 amino acids found in proteins. The amino acids mostly exist in the ionized form in the biological system.



Optical isomers of amino acids

If a carbon atom is attached to four different groups, it is asymmetric and therefore exhibits optical
isomerism. The amino acids (except glycine) possess four distinct groups (R, H, COO–, NH3+) held by α-carbon. Thus all the amino acids (except glycine where R = H) have optical isomers. The structures of L- and D-amino acids are written based on the configuration of L- and
D-glyceraldehyde. The proteins are composed of L-amino acids.


Classification of amino acids

There are different ways of classifying the amino acids based on the structure and chemical nature, nutritional requirement, metabolic fate etc.

A.    Amino acid classification based on the structure

B.    Classification of amino acids based on polarity

C.     Nutritional classification of amino acids

D.     Amino acid classification based on their metabolic fate


A.   Amino acid classification based on the structure

A comprehensive classification of amino acids is based on their structure and chemical nature. Each amino acid is assigned a 3 letter or 1 letter symbol. For example “Gly” or “G” for glycine and “Val” or “V” for valine etc. These symbols are commonly used to represent the amino acids in protein structure. The 20 amino acids found in proteins are divided into seven distinct groups.

1.      Amino acid with aliphatic R group:

These are monoamino monocarboxylic acids. This group consists of the most simple amino acids glycine, alanine, valine, leucine and isoleucine. Valine, leucine and isoleucine are branched chain amino acids.

2.      Hydroxyl (-OH) group-containing amino acids:

Serine, threonine, and tyrosine are -OH group-containing amino acids. Tyrosine being aromatic in nature is usually considered under aromatic amino acids.


3.   Sulfur-containing amino acids:

Cysteine with sulfhydryl group and methionine with thioether group are the two amino
acids incorporated during the course of protein synthesis. 

4.   Acidic amino acids and their amides:

Aspartic acid and glutamic acids are dicarboxylic monoamino acids while asparagine and glutamine are their respective amide derivatives.


5.   Basic amino acids:

The three amino acids lysine, arginine (with guanidino group) and histidine (with imidazole ring) are dibasic monocarboxylic acids. They are highly basic in character.

6.  Aromatic amino acids:

Phenylalanine, tyrosine, and tryptophan (with an indole ring) are aromatic amino acids.

7.   Imino acids:

Proline-containing pyrrolidine ring is a unique amino acid. It has an imino group (NH), instead of an amino group (NH2) found in other amino acids. Therefore, proline is an α-imino acid.

B.   Classification of amino acids based on polarity:

Amino acids are classified into 4 groups based on their polarity. Polarity is important for protein structure.

1. Non-polar amino acids:

These amino acids are also referred to as hydrophobic (water hating). They have no charge on the ‘R’ group. The amino acids included in this group are — alanine, leucine, isoleucine, valine, methionine, phenyl- alanine, tryptophan and proline.

2. Polar amino acids with no charge on ‘R’ group:

These amino acids, as such, carry no charge on the ‘R’ group and participate in hydrogen bonding of protein structure. The simple amino acid glycine (where R = H) is also considered in this category. The amino acids in this group are glycine, serine, threonine, cysteine, glutamine, asparagine and tyrosine.

3. Polar amino acids with positive ‘R’ group:

The three amino acids lysine, arginine and histidine are included in this group.
4. Polar amino acids with negative ‘R’ group:

The dicarboxylic monoamino acids— aspartic acid and glutamic acid are considered in this group.

 C.   Nutritional classification of amino acids:

The 20 amino acids are required for the synthesis of variety proteins, besides other
biological functions. However, all these 20 amino acids need not be taken in the diet. Based on the nutritional requirements, amino acids are grouped into two classes essential and non-
essential.

1.      Essential or indispensable amino acids:

The amino acids which cannot be synthesized by the body and, therefore, need to be supplied through the diet are called essential amino acids. The ten amino acids listed below are essential for humans (and also rats): Arginine, Valine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, and Tryptophan.

The two amino acids namely arginine and histidine can be synthesized by adults and not by growing children, hence these are considered as semi–essential amino acids. Thus, 8 amino acids are absolutely essential while 2 are semi-essential.

2.      Non-essential or dispensable amino acids:

The body can synthesize about 10 amino acids to meet the biological needs; hence they need not be consumed in the diet. These are glycine, alanine, serine, cysteine, aspartate, asparagine, glutamate, glutamine, tyrosine and proline.



C.   Amino acid classification based on their metabolic fate:

The carbon skeleton of amino acids can serve as a precursor for the synthesis of glucose (glycogenic) or fat (ketogenic) or both.

1.      Glycogenic amino acids:

These amino acids can serve as precursors for the formation of glucose or glycogen. E.g. alanine, aspartate, glycine, methionine etc.

2.      Ketogenic amino acids:

Fat can be synthesized from these amino acids. Two amino acids leucine and lysine are exclusively ketogenic.

Selenocysteine – the 21st amino acid

In recent years, a 21st amino acid namely selenocysteine has been added. It is found at the active sites of certain enzymes/proteins (selenoproteins).

Pyrrolysine – the 22nd amino acid

 In the year 2002, some researchers prescribed yet another amino acid namely Pyrrolysine as the 22nd amino acid present in protein.

Properties of amino acids

The amino acids differ in their physico–chemical properties which ultimately determine the characteristics of proteins.

A. Physical properties

1. Solubility: Most of the amino acids are usually soluble in water and insoluble in organic solvents.

2. Melting points: Amino acids generally melt at higher temperatures, often above 200°C.

3. Taste: Amino acids may be sweet (Gly, Ala, Val), tasteless (Leu) or bitter (Arg, Ile). Monosodium glutamate (MSG; Ajinomoto) is used as a flavoring agent in the food industry, and Chinese foods to increase taste and flavor.

4. Optical properties: All the amino acids except glycine possess optical isomers due to the presence of asymmetric carbon atom. Some amino acids also have a second asymmetric carbon e.g. isoleucine, threonine.

5. Amino acids as ampholytes: Amino acids contain both acidic (COOH) and basic (NH2) groups. They can donate a proton or accept a proton; hence amino acids are regarded as ampholytes.

Zwitterion or dipolar ion: The name Zwitter is derived from the German word which means hybrid. Zwitter ion (or dipolar ion) is a hybrid molecule containing positive and negative ionic groups.

In strongly acidic pH (low pH), the amino acid is positively charged (cation) while in strongly alkaline pH (high pH), it is negatively charged (anion). Each amino acid has a characteristic pH (e.g. leucine, pH 6.0) at which it carries both positive and negative charges and exists as zwitterion.

Isoelectric pH (symbol pI) is defined as the pH at which a molecule exists as a zwitterion or dipolar ion and carries no net charge. Thus, the molecule is electrically neutral.

Leucine exists as cation at pH below 6 and anion at pH above 6. At the isoelectric pH (pI = 6.0), leucine is found as zwitterion.

B. Chemical properties

Reactions due to ─COOH group

1.      Formation of salts and esters

Amino acids form salts (COONa) with bases and esters (COOR’) with alcohols.

2.      Decarboxylation

Amino acids undergo decarboxylation to produce corresponding amines. This reaction assumes significance in living cells due to the formation of many biologically important amines.

For example histamine and tyramine

3.      Reaction with ammonia

The carboxyl group of dicarboxylic amino acids reacts with NH3 to form amide

Aspartic acid + NH3   →Asparagine

Glutamic acid + NH3 →Glutamine

Reactions due to NH2 group

4. The amino groups behave as bases and combine with acids (e.g. HCl) to form salts (NH3+Cl –).

5. Reaction with ninhydrin: The D-amino acids react with ninhydrin to form a purple, blue or pink color complex (Ruhemann’s purple).

                        Amino acid + Ninhydrin →Keto acid + NH3 + CO 2 + Hydrindantin

                                      Hydrindantin + NH3 + Ninhydrin →Ruhemann’s purple

1.      Transamination: Transfer of an amino group from an amino acid to a keto acid to form a

new amino acid is a very important reaction in amino acid metabolism.

                        α- Ketoglutarate + Alanine → Glutamate + Pyruvate

2.      Oxidative deamination: The amino acids undergo oxidative deamination to liberate free

ammonia.

                                                   Glutamate → α- Ketoglutarate