Almost all amino acid residues can be oxidized by hydroxyl radicals, but only in several cases, the nature of the resulting substances is established. The table presents data on the oxidative modification of amino acid residues in proteins, the data are divided into groups:
Aromatic amino acids
Phenylalanine can be converted into mono and dihydroxy derivatives and tyrosine into 3.4-dihydroxy derivatives. These substances may also be subject to reverse oxidation/recovery and generate ROS. The radicals produced by tyrosine oxidation can also interact with each other to form dithirosines, resulting in the formation of intra- and intermolecular cross-links of peptides. The presence of 2.2'-biphenyl derivatives is considered to be a marker of protein damage induced by AFCs.
Irradiation of tryptophan by γ-radiation leads to the formation of different hydroxyl derivatives, formlkinurenines, and 3-hydroxynurenines. At UV irradiation, in the presence of peroxynitrite, ozone, Fe2+ and H2O2, tryptophan turns into kynurenine and N-formylkinurenin. Tryptophan and tyrosine are not the main targets for oxidation.
Residues of histidine, arginine, and lysine are particularly sensitive to ROS.
Amino acids forming carboxylic groups at the oxidation
Oxidation of lysine, arginine, histidine, and proline leads to the formation of aldehydic or ketone derivatives, and glutamic and asparagus acids to break the polypeptide chain to form a pyruvial group of N-terminal amino acid.
The oxidative rupture of the polypeptide chain along the path of α-amidation leads to the formation of a 2-ketoacyl derivative of N-terminal amino acid. In addition, carbonyl groups can be introduced into proteins as a result of interaction with reducing carbohydrates, carbohydrate oxidation products (glycoxidation and glycosylation reactions) or lipid oxidation products (Malone dialdehyde, 4-hydroxy-2-nominal). The formation of additional carbonyl groups makes it possible to determine the oxidation products of proteins with dinitrophenylhydrosine. Hydrazone is considered an indicator of free radical modification of proteins.
Amino acids containing sulfur (cysteine, methionine)
In the course of oxidation of cysteine residue, the derivatives of sulfenic, sulfenic and sulfonic acids are formed sequentially. Sulfenic derivatives can either oxidize to sulphine derivatives or form mixed esters with cysteine or glutamine. Sulfene-derived derivatives can be reduced to cysteine either enzymatically or non-enzymatically. It is believed that the formation of mixed esters (sulfenic k-ta with glutathione) may prevent further oxidation of sulfur.
Reactions with cysteine. The disulfide derivative (1) formed as a result of the glutathione disulfide metabolism reaction (2,3) becomes the initial form of cysteine-containing peptides. The final conversion products (1-3) are water and oxidized glutathione, followed by the renewal of reduced glutathione reserves. Then (4) the reaction is catalyzed by glutathione reductase and (5) NADPH is restored
Reactions with methionine. Its oxidation produces MetSox (methionine sulfoxide) (6). The enzyme methioninsulfonic acid reductase restores it to Met (7). The reducing components are supplied with thioredoxin (T(SH)2), NADPH is used for its regeneration. The reduction reaction of T(SH)2 is catalyzed by thioredoxin reductase (8).
Induced oxidation with cross-linking
Paths of stitching formation:
- Interaction of 2 alkyl radicals - derivative proteins, which are formed at the oxidation of peptide bonds or side parts of amino acid residues.
- Interaction of 2 tyrosyl radicals.
- Interaction of malonic and other dialdehydes with amino groups of lysine residues in molecules of two different proteins.
- Michael's reaction (HNE interaction product with cellular protein) with the amino group of a lysine residue of other protein.
- Interaction of the carbonyl group of glycation products of one protein with the amino group of a lysine residue of the other protein.
- Active oxidation of cysteine residues of 2 protein molecules.
Cross-linked proteins are not degraded by multicatalytic proteases or proteasomes, which may lead to an accumulation of oxidized proteins during aging and several pathologies. These complexes may inhibit other oxidized proteins.
Partial oxidation of proteins, leading to changes in their surface charge or hydrophobicity, maybe one of the mechanisms responsible for their spatial distribution in the cell.