Cysteine primary oxidation product

All amino-acid residues of proteins are potential targets for attack by reactive oxygen species (ROS) produced in the radiolysis of water however, in only a few cases have the oxidation products been fully characterized. Moreover, under most physiological conditions, cysteine, methionine, arginine, lysine, proline, histidine, and the aromatic amino acids are primary targets for ROS-mediated oxidation. 

Fig. 7. Oxidation products of proteins. The vertical structure in the middle represents the main peptide chain with amino acid side groups extending horizontally (M2). The a-carbons in the primary chain can be oxidized to form hydroperoxides. Reactions on the right side near the top exemplify oxidation of the primary chain leading to a peroxyl radical. Side chains represented are lysine, methionine, tyrosine, cysteine, and histidine, top to bottom, respectively. Modifications of the side chains and primary chain lead to carbonyl formation and charge modifications. If these reactions are not detoxified by antioxidants, they may propagate chain reactions within the primary chain, leading to fragmentation of the protein. See the text for details, o, represents reaction with oxygen RNS, reactive nitrogen species ROS, reactive oxygen species. Dense dot represents unpaired electron of radical forms.

Displacement of the sulfhydryl group in primary thiols, like L cysteine and 2-diethylaminoethanethiol, requires elemental fluorine, the most active oxidant Elemental sulfur is the major by-product in those reactions [7] (equation 2)... 

Primary and secondary products, and end-products of lipid peroxidation have all been shown to accumulate in senile cataracts (Babizhayev, 1989b Simonelli et al., 1989). Accumulation of these compounds in the lenticular epithelial membranes is a possible cause of damage preceding cataract formation. In senile cataracts there is also extensive oxidation of protein methionine and cysteine in both the membrane and cytosol components (Garner and Spector, 1980), while in aged normal lenses a lesser extent of oxidation was confined to the membrane. The authors therefore suggested that oxidation of membrane components was a precataract state. 

Primary amino acids will react with o-phthalaldehyde in the presence of the strongly reducing 2-mercaptoethanol (pH 9-11) to yield a fluorescent product (emission maximum, 455 nm excitation maximum, 340 nm). Peptides are less reactive than a-amino acids and secondary amines do not react at all. As a result, proline and hydroxyproline must first be treated with a suitable oxidizing agent such as chloramine T (sodium A-chloro-p-toluene-sulphonamide) or sodium hypochlorite, to convert them into compounds which will react. Similarly cystine and cysteine should also be first oxidized to cysteic acid. 

Azole approach. An important route for the synthesis of 3-hydroxypyridines is the reaction between a substituted furan and ammonia, or a primary amine. If the amino acid cysteine is used, the corresponding fused dihydrothiazole (479) can be obtained. Starting from optically active cysteine the corresponding cyclic enantiomer is obtained provided the fused product carries a 5-substituent, which for steric reasons prevents the otherwise ready racemization. A number of steps are involved in the overall reaction which may perhaps be rationalized by thiazolidine intermediates. The desired oxidation level in the substituted furan can either be reached by a-oxidation in an alkyl side-chain (499) or more generally by raising the furan ring itself to a higher oxidation level as in (500) (81H(15)1349). 

In that scheme, tyrosine is first oxidized to dopaquinone, the key intermediate for the formation of all melanins. If virtually no cysteine is present, then eumelanins are the primary products that arise through cychzation and oxidative polymerization, as described in the section on eumelanins. 

Sulfuric acid may be reduced to the level of sulfide and is then an important building stone of L-cysteine (see below). L-Cysteine, (S)- x-amino-/ -thiolpropionic acid, is one of the most important sulfur-containing substances in primary metabolism. The secondary products derived from L-cysteine may contain the sulfur in different states of oxidation. Of importance are sulfides (—S—), disulfides (—S—S— ), sulfenic acids (—S—OH), sulfoxides (—SO— ), sulfinic acids (—SO—OH) and sulfonic acids (—SO2—OH). 

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