Methionine sulphoxide reduction

McLafferty rearrangement 133, 163 Meisenheimer complexes 699, 702 Metal-chelated intermediates 838 Metal-halogen exchange 781, 784 Methionine, oxidation of 852-855 Methionine sulphone 853 Methionine sulphoxide 851-869 reduction of 1063 residues of... 

Although single-electron-transfer (SET) processes would be expected to be important in reactions that use metals as reagents, this type of process has also been recognized in the reduction of carbonyl groups that involve 1,4-dihydronicotinamide derivatives . Recent work by Oae and coworkers" has shown that an SET process is operative in the reduction of dibenzothiophene S-oxide by l-benzyl-l,4-dihydronicotinamide when the reaction is catalyzed by metalloporphins. The reaction is outlined in equation (18), but the study gave results of much more mechanistic than synthetic value. This type of study is relevant to understanding biochemical mechanisms since it is known that methionine sulphoxide is reduced to methionine by NADPH when the reaction is catalyzed by an enzyme isolated from certain yeasts . 

A recent study has described the inhibition of tyrosine nitration but not oxidation by tryptophan and tryptamine, indicating that nitration of the indole ring proceeds more favourably than nitration of the phenoxyl ring [118]. Methionine oxidation can be elicited by peroxynitrite and proceeds via two-step single electron reduction reactions yielding methionine sulphoxide as described previously [119]. 

Reducing equivalents from a ven thioredoxin can be donated to a variety of reductase enzymes. They are not specific for the nucleotide reductase or for enzymes from the same organism. Reduced yeast thioredoxin will serve as reductant for methionine sulphoxide reductase, sulphate reductase and the E. coli nucleoside diphosphate reductase. Heat-stable protein cofactors are known to be involved in each of these systems. 

The answer may lie in the fact that methionine is very sensitive to oxidation, and apPI which has been oxidized at this centre (a,-PI J is both a much less potent (Kj = 1.5 x 10 M) and slower acting (kassoc = 3.1 x 10 M" s ) inhibitor of HLE [45, 46], This decrease in activity can be rationalized by the fact that oxidation of the methionine sulphur to a sulphoxide increases the size and polarity of the P,-substituent. The increase in size may directly interfere with fitting this residue into the Spsubsite of HLE, and the change in polarity may cause a reduction in the net binding energy gained by the transition from a purely aqueous solution to a bound environment. 

The chemical and enzymatic browning reactions of plant polyphenols and their effects on amino acids and proteins are reviewed. A model system of casein and oxidizing caffeic acid has been studied in more detail. The effects of pH, time, caffeic acid level and the presence or not of tyrosinase on the decrease of FDNB-reactive lysine are described. The chemical loss of lysine, methionine and tryptophan and the change in the bioavailability of these amino acids to rats has been evaluated in two systems pH 7.0 with tyrosinase and pH 10.0 without tyrosinase. At pH 10.0, reactive lysine was more reduced. At pH 7.0 plus tyrosinase methionine was more extensively oxidized to its sulphoxide. Tryptophan was not chemically reduced under either condition. At pH 10.0 there was a decrease in the protein digestibility which was responsible for a corresponding reduction in tryptophan availability and partly responsible for lower methionine availability. Metabolic transit of casein labelled with tritiated lysine treated under the same conditions indicated that the lower lysine availability in rats was due to a lower digestibility of the lysine-caffeoquinone complexes. 

Protein-quinone reactions seem to have little influence on protein digestibility or on the bioavailability of tryptophan. Methionine does not appear to react covalently but may be extensively oxidized to its sulphoxide with some reduction in bioavailability. The reactions of cysteine were not investigated in our study because of the low level of cyst(e)ine in casein. Pierpoint (1969ab) has reported that cysteine reacts like lysine via a substitution into the quinone ring and it is also possible that cyst(e)ine residues may be oxidized (Finley and Lundin, 1980). 

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