Production of H 2 S, H 2 S n , and persulfide species (CysSSH and GSSH) by 3-mercaptopyruvate sulfurtransferase

Abstract

Accumulating evidence shows that hydrogen sulfide (H 2 S) has physiological roles in various tissues and organs, including the regulation of neuronal activity, vascular tension, a release of insulin, and protection of the heart, kidney, and brain from ischemic insult. H 2 S is produced from l -cysteine by pyridoxal 5'-phosphate (PLP)-dependent enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). 3-Mercaptopyruvate sulfurtransferase (3MST) is the third H 2 S-producing enzyme, and its substrate 3-mercaptopyruvate (3MP) is provided from l -cysteine and α-ketoglutarate (α-KG) by a PLP-dependent cysteine aminotransferase (CAT). An additional pathway for the production of H 2 S from d -cysteine metabolized by d -amino acid oxidase (DAO) together with 3MST has been identified. Recent studies have shown that hydrogen polysulfides (H 2 S n ) have been found to stimulate transient receptor potential ankyrin1 (TRPA1) channel, much more potently than does H 2 S. 3MST produces cysteine-persulfide (CysSSH) and its glutathione counterpart (GSSH), potential redox regulators, together with the potential signaling molecules H 2 S n . In addition, the interaction between H 2 S and nitric oxide (NO) also generates H 2 S n . These observations provide new insights into the production and physiological roles of these molecules.