The reverse transsulfuration pathway depicting the conversion of homocysteine to cysteine in reactions 5 and 6. Reaction 5 is catalyzed by cystathionine beta-synthase while reaction 6 is catalyzed by cystathionine gamma-lyase. The required homocysteine is synthesized from methionine in reactions 1, 2, and 3.
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.[1]
The forward pathway is present in several bacteria, such as Escherichia coli[2] and Bacillus 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 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[4]).
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.[5]
Humans are auxotrophic 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 as homocystinuria, due to homocysteine accumulation.
^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. PMID 24030774.{{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. PMID 21435402.
^Auger, S.; Yuen, W. H.; Danchin, A.; Martin-Verstraete, I. (2002). "The metIC operon involved in methionine biosynthesis in Bacillus subtilis is controlled by transcription antitermination". Microbiology. 148 (Pt 2): 507–518. doi:10.1099/00221287-148-2-507. hdl:10722/42040. PMID 11832514.
^Clausen, T.; Huber, R.; Laber, B.; Pohlenz, H. D.; Messerschmidt, A. (1996). "Crystal Structure of the Pyridoxal-5′-phosphate Dependent Cystathionine β-lyase fromEscherichia coliat 1.83 Å". Journal of Molecular Biology. 262 (2): 202–224. doi:10.1006/jmbi.1996.0508. PMID 8831789.
^Seiflein, T. A.; Lawrence, J. G. (2006). "Two Transsulfurylation Pathways in Klebsiella pneumoniae". Journal of Bacteriology. 188 (16): 5762–5774. doi:10.1128/JB.00347-06. PMC 1540059. PMID 16885444.
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standard amino acids. For example, homocysteine is formed through the transsulfurationpathway or by the demethylation of methionine via the intermediate metabolite...
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