MTA nucleosidase

FIG. 55 Methionine salvage pathway via 5 -methylthioadenosine (MTA). 1, MTA phosphorylase 2, MTA nucleosidase 3, 5-methylthioritese kinase. 

Two of the enzymes involved in the methionine cycle, namely, MTA nucleosidase [46] and MTR kinase [47] were purified from plants and characterised. However, the plant enzyme catalysing the formation of KMB from MTR-P has not been characterised. In rat liver extracts, three enzymes are involved in the conversion [42]. The first enzyme isomerizes MTR-P to l-phospho-5-methylthioribulose (MTRu-P), the second enzyme produces two unidentified metabolites from MTRu-P, and the third enzyme catalyses the conversion of these two metabolites to KMB with the uptake of oxygen. Plants may produce KMB from MTR-P by similar enzymes. The last step of the methionine cycle that converts KMB to methionine is most likely a transamination, and this activity was also detected in avocado extracts in the presence of asparagine [45]. 

While MTA nucleosidase and MTR kinase have been purified and characterized, the details of the biochemical conversion of MTR-l-P to KMB remain elusive. Here, the five-carbon ribose moiety of MTR is transformed into the four-carbon 2-ketobutyrate portion of KMB. Thus, one of the five carbons must be released. Recently Miyazaki and Y ang [ 19] have shown that the amounts of labeled HCOOH and methionine derived from methylthio [U- C] ribose catalyzed by an avocado extract are equivalent on a molar basis, indicating that the conversion involves a loss of formate, presumably from C-1 of MTR. This conversion of MTR to KMB and formate represents a 4-electron oxidation. While a stoichiometric consumption of O2 and production of formate was demonstrated in rat liver extracts, Miyazaki and Yang [19] were unable to observe such a requirement for molecular oxygen. 

Two classes of MTA nucleosidases have been reported in the Literature a hydrolytic nucleosidase that cleaves MTA into adenine and l ethylthioribose (MTR) has been described in Aerobacter aeroge-nes and in Escherichia coli and a phosphorolytic nucleosidase has been purified from several mammalian tissues i.e. rat ventral prostate, rat lung, human prostate and human placenta28. 

Fig. 5. Determination of the molecular weight of MTA nucleosidase by gel filtration. The dotted line indicates the of the nucleosidase (From Cacciapuoti et...

Fig, 7. Pathways for the metabolism of methionine to 5 -methylthioadenosine (MTA) and recycling of MTA to methionine. Methionine can serve as a carbon source for the synthesis of polyamines and, in some tissues, ethylene. 5 -Methylthioadenosine is a product of both processes. Only the methylthio group of methionine is recycled, the C4 moiety for the resynthesis of methionine being derived from the ribosyl moiety of ATP. The enzymes involved are (1) SAM synthetase, (2) SAM decarboxylase, (3) various C3 transfer enzymes of polyamine biosynthesis, (4) MTA nucleosidase, (5) methylthioribose kinase, (6) three( ) uncharacterized enzymes, (7) aminotransferase, and (8) aminocyciopropane carboxylate synthase. 

Scheme 6 S -Methylthioadenosine/5-adenosylhomocysteine nucleosidase (MTAN)-catalyzed hydrolysis of S -methylthioadenosine (MTA) to adenine and S-methylthio-D-ribose (MTR).

Recent data reported by Raina on the inhibition of MTA on spermine synthase from bovine brain are particularly interesting in that indicate that the nucleoside may play a role in the regulation of spermine synthesis in animal tissues. They also suggest that the thioether or its nucleosidase resistant derivatives, e.g. me-thylthiotubercidin and dimethylthioadenosine (see Fig. 8), could exert their effect also in vivo, therefore acting as possible antiproliferative agents. 

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