The production and role of hydrogen sulfide and hydrogen polysulfides in mammalian cells

Abstract

Accumulating evidence shows that hydrogen sulfide (H₂S) has physiological functions in various tissues and organs. It includes 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 beta-synthase (CBS) and cystathionine gamma-lyase (CSE). 3-Mercaptopyruvate sulfurtransferase (3MST) is the third H₂S-producing enzyme. 3-Mercaptopyruvate (3MP) is provided from L-cysteine and α-ketoglutarate by a PLP-dependent cysteine aminotransferase (CAT). An additional pathway for the production of H₂S from D-cysteine involving 3MST and D-amino acid oxidase (DAO) has been identified. Recently, hydrogen polysulfides (H₂S_n), which are oxidized forms of H₂S, have been found to stimulate transient receptor potential ankyrin1 (TRPA1) channel, much more potently than H₂S. H₂S_n is produced from 3MP by 3MST. In addition to the enzymatic production, the interaction between H₂S and nitric oxide (NO), another gaseous signaling molecule, also generates H₂S_n. These observations provide new insight into the production of these molecules and their mechanisms of physiological functions.