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Transsulfuration pathway

Metabolic pathway involving the transfer of a thiol group

Metabolic pathway involving the transfer of a thiol group

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{{Cite journal | doi-access = free | hdl-access = free 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.{{Cite journal 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).

Role of pyridoxal phosphate

All four transsulfuration enzymes require vitamin B6 in its active form (pyridoxal phosphate or PLP). Three of these enzymes (cystathionine γ-synthase excluded) are part of the Cys/Met metabolism PLP-dependent enzyme family (type I PLP enzymes).

Direct sulfurization

The direct sulfurylation pathways for the synthesis of cysteine or homocysteine proceeds via the replacement of the acetyl/succinyl group with free sulfide (via the cysK or cysM -encoded cysteine synthase. and the metZ or metY -encoded homocysteine synthase,{{Cite journal

References

References

  1. Weekley, C. M. and Harris, H. H.. (2013). "Which form is that? The importance of selenium speciation and metabolism in the prevention and treatment of disease". Chem. Soc. Rev..
  2. (2004). "Structure and Mechanism of O-Acetylserine Sulfhydrylase". Journal of Biological Chemistry.
  3. (2014). "Bacterial methionine biosynthesis". Microbiology.
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nitrogen-cycle sulfur-metabolism metabolic-pathways
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