Methionine Metabolism

Methionine metabolism in mammals consists of 2 pathways, the methionine cycle and the transsulfuration sequence. These pathways share 3 common reactions with both including the conversion of methionine to S-adenosylmethionine (SAM),the utilization of SAM in diverse transmethylation reactions yielding a methylated product plus S-adenosylhomocysteine, and the cleavage of S-adenosylhomocysteine to yield homocysteine and adenosine. The transulfuration reactions that produce cysteine from homocysteine and serine also produce α-ketobutyrate, the latter being converted first to propionyl-CoA and then via a 3-step process to succinyl-CoA. Regulation of the methionine metabolic pathway is based on the availability of methionine and cysteine. If both amino acids are present in adequate quantities, SAM accumulates and is a positive effector on cystathionine synthase, encouraging the production of cysteine and α-ketobutyrate (both of which are glucogenic). However, if methionine is scarce, SAM will form only in small quantities, thus limiting cystathionine synthase activity.

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