Methionine S-oxides

This enzyme [EC 1.8.4.5], also known as methionine S-oxide reductase, catalyzes the reaction of L-methionine with oxidized thioredoxin to produce L-methionine S-oxide and reduced thioredoxin. Dithiothreitol can substitute for reduced thioredoxin in the reverse reaction. In addition, other methyl sulfoxides can replace methionine sulfoxide in the reverse reaction. 

Butanoic acid, 2-amino-4-(methyisulfonyl>- methionine suifone methionine S-oxide H3C-S0-(CH2)2-CH(NH2)-C00H 3729 ... 

In rheumatoid arthritis the damage that is found in joints may also be a result of the inactivation of a-1-PI due to the oxidation of an essential methionine(s) residue in this protein. It has been found that a-l-PI purified from the synovial fluid of patients with rheumatoid arthritis contained four Met(O) residues and was not able to form a binary complex with elastase89. It is probable that the presence of the Met(Oj residues in a-l-PI from these patients results from a high level of oxidants produced by neutrophils in the inflammed joint. 

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 . 

Nunn JE Chanarin I Nitrous oxide inactivates methionine s)mthetase. In Eger El (ed) Nitrous Oxide, pp 211-233. New York, Elsevier, 1985... 

Tab. 53 (S. 429) zeigt einige exemplarische Beispiele1. Die dort angefiihrten, von Methionin abgeleiteten 4-Oxo-imidazolidine bilden - fiber die Oxidation zum S-Oxid, gefolgt von thermischer /LEliminierung - ein Potential zur Synthese von 2-Alkyl-2-amino-3-alkensauren z. B. (R)-2-Araino-2-cthyl-3-butensaure (30% fiber 3 Stufen). Experimentelle Einzelheiten entnehme man der Originalliteratur2-3.

Fig. 5.18. 360 MHz H NMR spectra of oxidized horse heart cytochrome c. The labeled signals are assigned to a = 8-CH3, b = 3-CH3, c = 5-CH3, d = thioether bridge 2-CH3, e = axial methionine S-CH3 the resonances at 7.4 ppm (1-CH3) and 3.1 ppm (thioether bridge 4-CH3) are not shown. Chemical shifts are in ppm from DSS (adapted from [42]) (labeling as in Fig. 5.7B).

Mass increase is consistent with oxidation of methionine(s). N-D. - detected. 

I etrahydrofolate, a carrier of activated one-carbon units, plays an important role in the metabolism of amino acids and nucleotides. This coenzyme carries one-carbon units at three oxidation states, which arc interconvertible most reduced—methyl intermediate methylene and most oxidized—formyl, form i mi no, and methenyl. The major donor of activated methyl groups is S-adenosylmethionine, which is synthesized by the transfer of an adenosyl group from ATP to the sul-lur atom of methionine. S-Adenosylhomocysteine is formed when the activated methyl group is transferred to an acceptor. It is hydrolyzed to adenosine and homocysteine, and the latter is then methylated to methionine to complete the activated methyl cycle. 

We have not found fluoride, manganese, or 5 -AMP to be essential for TPST-1 or TPST-2 activity. Dithiothreitol (DTT) is also optional as precaution for preventing possible methionine oxidation if peptides contain methionine (s). 

Homoserine also has been detected in filtrates of liver preparations incubated with methionine. Cantoni provisionally identified homoserine as a product of the acid hydrolysis of active methionine (S-adeno-sylmethionine). Beyond homoserine, the postulated reactions 2 and 3 are still more speculative. It might be presumed that homoserine is oxidized to aspartic acid, in analogy to the observations on the catabolism of lysine, in which the analogous a-amino adipic acid is an intermediate. If aspartic acid is formed, the subsequent reaction sequence is readily apparent. Evidence favorable to the proposed reaction pathway is the finding of Marshall and Friedberg, of the occurrence of a small amount of fumaric acid, labeled in the methine carbons, from the livers of mice injected with DL-methionine-2-C. ... 

Methodfor sulfur-containing amino acids. Moore (12) determined cysteine and cystine as cysteic acid by performic acid oxidation. However, methionine can also be determined as methionine S,S-dioxide. 

Compound 20 upon oxidation, leads to an SAN bonded intermediate 20 (ox) with /max 400 nm and /1/2 0.5-2 ps (depending on pH). This clearly resembles the methionine data. Oxidation of 21, on the other hand, yields a transient 21 (ox) with 2n,ax t 340 nm and a halflife of about 26 ps, assigned to the >SaO(0)C- bonded species. Furthermore, 20(ox) decarboxylates directly, while 21 (ox) appears to deprotonate (at C, a to S). It is noted that decarboxylation also occurs from the oxidized endo-carboxylate, but not via the >SaO(0)C- species. A more complex and concerted mechanism, involving a... 

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