File:Biomolecules-10-00697-g001.jpg
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[edit]DescriptionBiomolecules-10-00697-g001.jpg |
English: Role of CBS and other enzymes in the regulation of mammalian sulfur amino acid metabolism. Methionine (Met), an essential amino acid taken from dietary proteins, is condensed with ATP by methionine adenosyltransferase (MAT) to form S-adenosylmethionine (SAM). SAM serves as a universal methyl donor for multiple methylation reactions catalyzed by various methyltransferases (MT) yielding methylated product and S-adenosylhomocysteine (SAH). SAH is subsequently hydrolyzed by SAH hydrolase (SAHH) into adenosine and homocysteine (Hcy). Hcy is then distributed between two competing pathways. To conserve Met, Hcy is remethylated back to Met by the action of either liver-dependent betaine homocysteine methyltransferase (BHMT) or ubiquitous methionine synthase (MS) using betaine and methyl tetrahydrofolate (methyl-THF), respectively, as the methyl donor. To generate Cys, Hcy is irreversible diverted from the methionine cycle to the transsulfuration pathway by cystathionine beta-synthase (CBS)-catalyzed condensation with serine (Ser) forming cystathionine (Cth), which is subsequently hydrolyzed by cystathionine gamma-lyase (CSE, an enzyme also referred to as “CGL” in the literature) into cysteine (Cys). Importantly, SAM regulates the flux of Hcy through the competing pathways by allosteric activation of CBS and inhibition of methylenetetrahydrofolate reductase (MTHFR). Interestingly, all enzymes of the transsulfuration pathway and the remethylation (folate cycle) enzymes require assistance of a member of vitamin B family: B2 (riboflavin) in MTHFR, B6 (pyridoxine) in serine hydroxymethyltransferase (SHMT), CBS and CSE, B9 (folic acid) as a one-carbon carrier of the remethylation cycle, or B12 (cobalamin) in MS. |
Date | |
Source | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277093/ |
Author | Karim Zuhra, Fiona Augsburger,Tomas Majtan, and Csaba Szabo |
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current | 17:38, 17 July 2023 | 763 × 727 (93 KB) | Ozzie10aaaa (talk | contribs) | Uploaded a work by Karim Zuhra, Fiona Augsburger,Tomas Majtan, and Csaba Szabo from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277093/ with UploadWizard |
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