The transsulfuration pathway is a

metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell (biology), cell. The reactants, products, and Metabolic intermediate, intermediates of an enzymatic reaction are known as metabolites, which are ...

involving the interconversion of

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

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 ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

'' and ''

Bacillus subtilis ''Bacillus subtilis'' (), known also as the hay bacillus or grass bacillus, is a gram-positive, catalase-positive bacterium, found in soil and the gastrointestinal tract of ruminants, humans and marine sponges. As a member of the genus ''Bacill ...

'', 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 Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell. Pyruvic ...

and ammonia (catalysed by the metC-encoded cystathionine β-lyase). The production of homocysteine through transsulfuration allows the conversion of this intermediate to

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other non-essential amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine play ...

, 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, 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.

Role of pyridoxal phosphate

All four transsulfuration enzymes require

vitamin B6 Vitamin B6 is one of the B vitamins, and is an essential nutrient for humans. The term essential nutrient refers to a group of six chemically similar compounds, i.e., "vitamers", which can be interconverted in biological systems. Its active f ...

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,

References

{{reflist, refs= {{cite journal , vauthors = Ferla MP, Patrick WM , title = Bacterial methionine biosynthesis , journal = Microbiology , volume = 160 , issue = Pt 8 , pages = 1571–84 , year = 2014 , pmid = 24939187 , doi = 10.1099/mic.0.077826-0 , doi-access = free Nitrogen cycle Sulfur metabolism Metabolic pathways