methionine metabolism (trans-sulfuration pathway)

The trans-sufuration pathway serves to interconvert the sulfur amino acids cysteine, homocysteine & methionine & also functions in the activated methyl cycle. S-adenosylmethionine (SAM) is the major donor of methyl groups in mammals. N5-methyl tetrahydrofolate (THF) can can donate methyl groups, but its transfer potential is insufficient for most biosynthetic methylations.* The methyl group on methionine of SAM is activated by the positive charge of the adjacent sulfur atom. Methyl acceptors from SAM include phosphatidylethanolamine, catecholamines & lysine residues of proteins in the biosynthesis of carnitine. * Note that N5-methyl THF is the methyl donor in the conversion of homocysteine to methionine. * This results in formation of THF. * The THF is in turn used by serine hydroxymethyltransferase for the formation of N5,N10-methylene-tetrahydrofolate used by thymidylate synthase in the biosynthesis of TMP (thymidine monophosphate), a precursor for DNA synthesis. Methionine synthase catalyzes a vitamin B12 (methylcobalamin)-dependent reaction. Regeneration of tetrahydrofolate is essential for activity of thymidylate synthase & DNA synthesis. Vitamin B12 plays no other role in DNA synthesis. An alternate reaction catalyzed by betaine-homocysteine methyltransferase also catalyzes homocysteine to methionine (see homocysteine). Serine hydroxymethyltransferase catalyzes formation of 5,10-methylenetetrahydrofolate & glycine from serine & tetrahydrofolate. The methylenetetrahydrofolate is, in turn used by thymidylate synthase in the biosynthesis of dTMP from dUMP. * see figure Biochemistry: - methionine metabolism 1 - enzyme methionine adenosyltransferase - substrate methionine + ATP - product S-adenosylmethionine + H2P2O7-2 + H2PO4- - methionine metabolism 1b - substrate 3 S-adenosylmethionine + phosphatidylethanolamine - product 3 S-adenosylhomocysteine + phosphatidylcholine - methionine metabolism 2 - enzyme adenosylhomocysteinase - substrate S-adenosylhomocysteine - product homocysteine + adenosine + H₂O - methionine metabolism 3 - enzyme cystathionine beta-synthase - substrate homocysteine + serine - product cystathionine + H₂O - methionine metabolism 4 - enzyme cystathioninase - substrate cystathionine)) - product cysteine + alpha-ketobutyrate + NH₃ - methionine metabolism 5 - enzyme methionine synthase - substrate homocysteine + 5-methyltetrahydrofolate - product methionine + tetrahydrofolate - methionine metabolism 6 - enzyme serine hydroxymethyltransferase - substrate tetrahydrofolate + serine - product N5,N10-methylene tetrahydrofolate + glycine - methionine metabolism 7 - enzyme methylenetetrahydrofolate reductase - substrate N5,N10-methylene tetrahydrofolate + NADPH - product N5-methyl tetrahydrofolate + NAD⁺ - methionine metabolism 8 - enzyme betaine homocysteine-S-methyltransferase - substrate homocysteine + betaine - product methionine + dimethylglycine

Related

folate metabolism methionine

General

biosynthetic pathway or anabolic pathway catabolic pathway

References

Ref: Stryer Biochemistry WH Freeman & Co, New York, 1988 pg 582-84