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The transsulfuration pathway is a metabolic pathway involving the interconversion of cysteine and homocysteine through the intermediate cystathionine. Two transsulfurylation pathways are known: the forward and the reverse.
The forward pathway is present in several bacteria, such as Escherichia coli and Bacillus subtilis, and involves the transfer of the thiol group from cysteine to homocysteine (methionine precursor with the S-methyl group), thanks to the γ-replacement of the acetyl or succinyl group of a homoserine with cysteine via its thiol group to form cystathionine (catalysed by cystathionine γ-synthase, which is encoded by metB in E. coli and metI in B. subtilis). Cystathionine is then cleaved by means of the β-elimination of the homocysteine portion of the molecule leaving behind an unstable imino acid, which is attacked by water to form pyruvate and ammonia (catalysed by the metC-encoded cystathionine β-lyase). The production of homocysteine through transsulfuration allows the conversion of this intermediate to methionine, through a methylation reaction carried out by methionine synthase.
The reverse pathway is present in several organisms, including humans, and involves the transfer of the thiol group from homocysteine to cysteine via a similar mechanism. In Klebsiella pneumoniae the cystathionine β-synthase is encoded by mtcB, while the γ-lyase is encoded by mtcC. Humans are auxotrophic for methionine, therefore it's considered to be an essential amino acid. However humans are autotrophic for cysteine due to the reverse trans-sulfurylation pathway, meaning that cysteine is not considered to be an essential amino acid.
Mutations in the CBS pathway can cause a condition known as homocystinuria, an outcome of higher homocysteine levels (hyperhomocysteinemia).
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