Thetranssulfuration pathway is ametabolic pathway involving the interconversion ofcysteine andhomocysteine through the intermediatecystathionine. Two transsulfurylation pathways are known: theforward and thereverse.[1]
Theforward pathway is present in several bacteria, such asEscherichia coli[2] andBacillus subtilis,[3] 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 ahomoserine with cysteine via its thiol group to form cystathionine (catalysed bycystathionine γ-synthase, which is encoded bymetB inE. coli andmetI inB. subtilis). Cystathionine is then cleaved by means of the β-elimination of the homocysteine portion of the molecule leaving behind an unstableimino acid, which is attacked by water to formpyruvate and ammonia (catalysed by the metC-encodedcystathionine β-lyase[4]).The production of homocysteine through transsulfuration allows the conversion of this intermediate tomethionine, through a methylation reaction carried out bymethionine synthase.
Thereverse pathway is present in several organisms, including humans, and involves the transfer of the thiol group from homocysteine to cysteine via a similar mechanism. InKlebsiella pneumoniae thecystathionine β-synthase is encoded bymtcB, while theγ-lyase is encoded bymtcC.[5]Humans areauxotrophic for methionine, hence it is called an "essential amino acid" by nutritionists, but are not for cysteine due to the reverse trans-sulfurylation pathway. Mutations in this pathway lead to a disease known ashomocystinuria, due to homocysteine accumulation.
All four transsulfuration enzymes requirevitamin B6 in its active form (pyridoxal phosphate or PLP). Three of these enzymes (cystathionine γ-synthase excluded) are part of theCys/Met metabolism PLP-dependent enzyme family (type I PLP enzymes).There are five different structurally related types of PLP enzymes. Members of this family belong to the type I and are:[6]
The direct sulfurylation pathways for the synthesis of cysteine or homocysteine proceeds via the replacement of the acetyl/succinyl group with free sulfide (via thecysK orcysM -encoded cysteine synthase.[7] and themetZ ormetY -encoded homocysteine synthase,[8]
^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.42 (23):8870–8894.doi:10.1039/c3cs60272a.PMID24030774.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^Aitken, S. M.; Lodha, P. H.; Morneau, D. J. K. (2011). "The enzymes of the transsulfuration pathways: Active-site characterizations".Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics.1814 (11):1511–7.doi:10.1016/j.bbapap.2011.03.006.PMID21435402.
