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Pathway Description
Methionine Metabolism and Salvage
Saccharomyces cerevisiae
Metabolic Pathway
The biosynthesis of methionine begins with aspartate being phosphorylated into L-aspartyl-4-phosphate through an ATP driven aspartate kinase. L-Aspartyl-4-phosphate is then catabolized through an NADPH-dependent aspartic beta-semialdehyde dehydrogenase resulting in the release of L-aspartate semialdehyde which is transformed into a homoserine through a homoserine dehydrogenase. Homeserine, in turn, is acetylated through a homoserine O-trans-acetylase resulting in the release of O-acetyl-L-homoserine.
The latter compound interacts with hydrogen sulfide through an O-acetylhomoserine (thiol)-lyase resulting in the release of L-homocysteine. The latter compound then reacts with 5-methylterahydropteroyltri-L-glutamate through an N5-methyltetrahydropteroyltrigluatamate homocysteine methyltransferase resulting in the release of a tetrahydropteroyltri-l-glutamate and methionine. The degradation of methionine begins with methionine being used to synthesize S-adenosylmethionine through an S-adenosylmethionine synthetase. The S-adenosylmethionine reacts with a demethylated methyl donor resulting in the release of a methylated methyl donor, a hydrogen ion, and an S-adenosylhomocysteine. The latter compound then reacts with an S-adenosyl-L-homocysteine hydrolase resulting in the release of adenosine and homocysteine where the cycle can begin again. The salvage of methionine begins with S-methyl-5'-thioadenosine (a product of spermine biosynthesis) being phosphorylated through a 5-methylthioadenosine phosphorylase resulting in the release of adenine and S-methyl-5-thio-alpha-D-ribose 1-phosphate. This last compound is isomerized into 5-methylthioribulose 1-phosphate. The latter compound is then dehydrated through a methylthioribulose 1-phosphate dehydratase resulting in 5-(methylthio)-2,3-dioxopentyl 1-phosphate. This resulting compound is then dephosphorylated through a 2,3-dioxomethiopentane-1-phosphate enolase/phosphatase resulting in a 1,2-dihydroxy-5-(methylthio)pent-1-en-3-one. This latter compound can react spontaneously or through an acireductone dioxygenase resulting in the release of a 2-oxo-4-methylthiobutanoate. This latter compound is then turned into methionine through an aromatic amino acid aminotransferase II.
References
Methionine Metabolism and Salvage References
Griffith OW: Mammalian sulfur amino acid metabolism: an overview. Methods Enzymol. 1987;143:366-76.
Pubmed: 3309559
Pirkov I, Norbeck J, Gustafsson L, Albers E: A complete inventory of all enzymes in the eukaryotic methionine salvage pathway. FEBS J. 2008 Aug;275(16):4111-20. doi: 10.1111/j.1742-4658.2008.06552.x. Epub 2008 Jul 10.
Pubmed: 18625006
Thomas D, Surdin-Kerjan Y: Metabolism of sulfur amino acids in Saccharomyces cerevisiae. Microbiol Mol Biol Rev. 1997 Dec;61(4):503-32.
Pubmed: 9409150
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