Cysteine sulfur, oxidation mechanisms

The known occurrences of thioaldehydes in biochemistry are few. One well-studied example is the involvement of a thioaldehyde in the decarboxylation of cysteine in phosphopantothenoyl-cysteine during coenzyme A biosynthesis. In the proposed mechanism for this decarboxylation, a thioaldehyde is generated at the cysteine sulfur by a flavin-dependent oxidation of the thiol. The resulting /3-thioketo acid, acting like a /3-keto acid, facilitates the decarboxylation of the amide-bound cysteine in phosphopantothenoyl-cysteine substrate. Finally, the flavinH2 produced in the thiol oxidation is used to reduce the thioaldehyde back to the thiol. 

B. OXIDATION MECHANISMS OF CYSTEINE SULFUR Direct Oxidation of Cysteine Sulfur... 

A reasonable mechanism for the iodine oxidation of 5-Trt cysteine peptides is given in Scheme 6. 45 Reaction of iodine with the divalent sulfur atom leads to the iodosulfonium ion 5 which is then transformed to the sulfenyl iodide 6 and the trityl cation. Sulfenyl iodides are also postulated as intermediates in the iodine oxidation of thiols to disulfides. The disulfide bond is then formed by disproportionation of two sulfenyl iodides or by reaction between the electrophilic sulfur atom of R -S-I and the nucleophilic S-atom of a second R -S-Trt molecule. The proposed mechanism suggests that any sulfur substitution (i.e., thiol protecting group) capable of forming a stabilized species on cleavage, such as the trityl cation, can be oxidatively cleaved by iodine. 

The proposed mechanism of the oxidative cleavage of S-protecting groups by the chlorosilane/sulfoxide procedure is outlined in Scheme 8. 95 The first reaction is considered to be formation of the sulfonium cation 9 from diphenyl sulfoxide (7) and the oxygenophilic silyl compound 8. The formation of a sulfonium ion of this type is known and has been utilized for the reduction of sulfoxides. 97 Subsequent electrophilic attack of 9 on the sulfur atom of the S-protected cysteine residue leads to the formation of intermediate 10, whereby the nature of the silyl chloride employed should be the main factor that influences the electrophilicity of 9. The postulated intermediate 10 may then act as the electrophile and react with another S-protected cysteine residue to generate the disulfide 11 and the inert byproduct diphenyl sulfide (12). This final step is analogous to the reaction of a sulfenyl iodide as discussed in Section 6.1.1.2.1. 

The oxidation of glutamic acid to cyanopropionic acid with CAB in acid solution showed an inverse fractional dependence on acidity. Similarly in alkaline medium, the order in alkali is fractional inverse.143 Kinetics of ruthenium(III)-catalysed oxidation of diols with CAB have been obtained. The products arise due to a fission of the glycol bond.144 The oxidation of isatins with CAB, in alkaline solutions, showed a first-order dependence on CAB and isatin and fractional order in alkali. The rates correlate with the Hammett relationship, the reaction constant p being —0.31. The observed results have been explained by a plausible mechanism and the related rate law has been deduced.145 The oxidation of cysteine with CAB in sulfuric acid medium is first order in CAB and cysteine and the rate is decreased with an increase in the hydrogen ion concentration.146... 

Melanin granules are secreted by melanocytes in the hair papilla and distributed to keratin in the hair cortex and inner layers of the hair sheath during normal development. Melanogenesis is subject to hormonal control and has been the focus of intensive genetic studies. Two main forms of melanin exist in human skin—eumelanin and phaeomelanin, both of which are derived from tyrosine through the action of tyrosinase (a cupro-enzyme) and possibly other key enzymes (with nickel, chromium, iron, and manganese as cofactors). Tyrosine is converted to dihydroxyphenylalanine and, via a series of intermediate steps, to indole-5,6-quinone, which polymerizes to eumelanin. Phaeomelanins are produced by a similar mechanism but with the incorporation of sulfur (as cysteine) by a nonenzymatic step in the oxidation process. 

Selenium is an essential trace element and an integral component of heme oxidase. It appears to augment the antioxidant action of vitamin E to protect membrane lipids from oxidation. The exact mechanism of this interaction is not known however, selenium compounds are found in the selenium analogs of the sulfur-containing amino acids, such as cysteine and methionine. Se-cysteine is found in the active sites of the enzyme glutathione peroxidase, which acts to use glutathione to reduce organic hydroperoxides. 

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