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

Abstract

Accumulating evidence shows that hydrogen sulfide (H2S) 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. H2S 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 H2S-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 H2S from d-cysteine metabolized by d-amino acid oxidase (DAO) together with 3MST has been identified. Recent studies have shown that hydrogen polysulfides (H2Sn) have been found to stimulate transient receptor potential ankyrin1 (TRPA1) channel, much more potently than does H2S. 3MST produces cysteine-persulfide (CysSSH) and its glutathione counterpart (GSSH), potential redox regulators, together with the potential signaling molecules H2Sn. In addition, the interaction between H2S and nitric oxide (NO) also generates H2Sn. These observations provide new insights into the production and physiological roles of these molecules.