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

Hydrogen sulfide (H2S) acts as a signaling molecule and cytoprotectant. H2S 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 H2S 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 H2S 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 H2O2 and attenuated ischemia–reperfusion injury in the kidney more than l-cysteine. The present study presents a novel pathway of H2S production and provides a new therapeutic approach to deliver H2S to specific tissues. [ABSTRACT FROM AUTHOR]