P33 A novel pathway for the production of hydrogen sulfide from d-cysteine in mammalian cells

Abstract

Hydrogen sulfide (H 2 S) acts as a signaling molecule and cytoprotectant. H 2 S is known to be produced from l -cysteine by two pyridoxal 5′-phosphate (PLP)-dependent enzymes, cystathionine beta-synthase and cystathionine gamma-lyase. We recently demonstrated that 3-mercaptopyruvate sulfurtransferase (3MST) produces H 2 S from 3-mercaptopyruvate (3MP), which is provided from l -cysteine and alpha-ketoglutarate by PLP-dependent cysteine aminotransferase (CAT). We also found an additional pathway for the production of H 2 S from d -cysteine involving 3MST and d -amino acid oxidase (DAO). The enzymatic activities associated with d -cysteine are distinct from those of l -cysteine with respect to the optimal pH and dependency on PLP. Unlike the l -cysteine pathway, this d -cysteine-dependent pathway seems to operate predominantly in the cerebellum and the kidney. Administration of d -cysteine protected primary cultures of cerebellar neurons from oxidative stress induced by H 2 O 2 and attenuated ischemia–reperfusion injury in the kidney more than l -cysteine. The present study presents a novel pathway of H 2 S production and provides a new therapeutic approach to deliver H 2 S to specific tissues.