BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 5. STRUCTURE, PROPERTIES, AND FUNCTIONS OF PROTEINS

5.1. Structure and properties of amino acids making up proteins. Peptide bonds

5.1.2. Classification of amino acids

Classification of Amino acids According to the Chemical Structure of their side chains (radicals). Based on their chemical structure, Amino Acids are divided into aliphatic, aromatic, and heterocyclic (Table 5.1).

Class="center">Table 5.1

Classification of standard Proteinogenic Amino Acids by chemical structure

Aliphatic side chains may contain functional groups that confer specific properties upon them, such as carboxyl, amino, thiol, amide, hydroxyl, and guanidino groups.

Amino acid names can be constructed using substitutive nomenclature, but trivial (common) names are generally used (Table 5.2).

Table 5.2

Examples of amino acid names according to substitutive nomenclature and their corresponding trivial names

Three-letter Abbreviations of their trivial names are used to denote amino acid residues in Peptide and Protein molecules, and in some cases, single-letter symbols are also used (Table 5.1).

Trivial names of amino acids often originate from the source from which they were first isolated or from the specific Properties of the amino acid. For instance, Serine was first isolated from Silk Fibroin (from Lat. sericum - silky), and Glycine got its name due to its sweet taste (from Gr. glykos - sweet).

Classification of amino acids based on the Water solubility of their side chains. All 20 amino acids found in human Proteins can be grouped according to the ability of their side chains to dissolve in water. These side chains can be arranged in a continuous continuum starting with fully hydrophobic and ending with fully hydrophilic amino acids.

The Solubility of Amino acid side chains is determined by the polarity of the functional groups that make up the molecule (polar groups attract water, while non-polar groups repel it).

Amino acids with non-polar side chains. Non-polar (hydrophobic) side chains include those with aliphatic hydrocarbon chains (Alanine, valine, leucine, isoleucine, Proline, and Methionine side chains) and aromatic rings (phenylalanine and Tryptophan side chains). In water, such amino acid side chains tend to associate with each other or with other hydrophobic molecules, thereby minimizing their contact surface area with water.

Amino acids with polar uncharged side chains. These side chains are more soluble in water than hydrophobic side chains because they contain polar functional groups capable of forming Hydrogen Bonds with water. They include serine, Threonine, and Tyrosine, which contain hydroxyl groups; asparagine and glutamine, containing amide groups; and Cysteine with its sulfhydryl group.

Cysteine and tyrosine contain sulfhydryl and hydroxyl groups, respectively, which are capable of dissociation to release H⁺. At a pH of about 7.0, maintained within Cells, these groups practically do not dissociate.

Amino acids with polar negatively charged side chains. This group includes aspartic and glutamic acids, which possess an additional carboxyl group in their side chain. At a pH around 7.0, they dissociate to form COO^- and H⁺. Consequently, the side chains of these amino acids exist as anions. The ionized forms of aspartic and glutamic acids are referred to as aspartate and glutamate, respectively.

Amino acids with polar positively charged side chains. Lysine and Arginine contain an additional positively charged group in their side chain. In lysine, the second amino group capable of binding H⁺ is located at the ε-position of the aliphatic chain. In arginine, the guanidino group acquires a positive charge. Histidine contains a weakly ionized imidazole group; therefore, under physiological pH fluctuations (from 6.9 to 7.4), it is charged either neutrally or positively. When the concentration of protons in the medium increases, the histidine imidazole group can bind a proton, acquiring a positive charge, whereas an increase in the concentration of hydroxyl groups causes it to release a proton, losing the positive charge of the side chain. Positively charged side chains are cations (see scheme). Polar charged amino acid side chains are the most water-soluble.

Change in the net charge of amino acids depending on the pH of the medium. At neutral pH values, all acidic (proton-donating) and all basic (proton-accepting) functional groups are in a dissociated state.

Therefore, in a neutral medium, amino acids with a non-dissociating radical have a net zero charge, those with acidic functional groups carry an overall negative charge, and amino acids containing basic functional groups have a positive charge (Table 5.3).

Table 5.3

Changes in the net charge of amino acids depending on the pH of the medium

A shift in pH toward the acidic range (i.e., an increase in H⁺ ions in the medium) suppresses the dissociation of acidic groups. In a strongly acidic environment, all amino acids acquire a positive charge. Conversely, an increase in the concentration of OH^- groups causes the release of H⁺ from basic functional groups, leading to a decrease in the positive charge.

Modified amino acids present in proteins. Only the 20 listed amino acids are directly involved in Protein Synthesis in The Human Body. However, Some proteins contain non-standard, modified amino acids which are derivatives of one of the 20 basic amino acids. For example, the Collagen molecule (a fibrillar protein of the Extracellular matrix) contains hydroxy derivatives of lysine and proline: 5-hydroxylysine and 4-hydroxyproline:

Modifications of amino acid residues occur within already formed proteins, that is, only after their synthesis is complete. The Introduction of additional functional groups into the Structure of Amino acids imparts properties to proteins that are essential for the performance of their specific Functions. For instance, γ-carboxyglutamic acid is a component of proteins involved in Blood clotting, where two adjacent carboxyl groups in their structure are required for binding protein factors to Ca²⁺ ions. Impaired carboxylation of glutamate leads to a decrease in blood coagulability.