title: A novel pathway for the production of hydrogen sulfide from D-cysteine in mammalian cells.
abstract: In eukaryotes, hydrogen sulphide acts as a signalling molecule and cytoprotectant. Hydrogen sulphide is known to be produced from L-cysteine by cystathionine β-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase coupled with cysteine aminotransferase. Here we report an additional biosynthetic pathway for the production of hydrogen sulphide from D-cysteine involving 3-mercaptopyruvate sulfurtransferase and D-amino acid oxidase. Unlike the L-cysteine pathway, this D-cysteine-dependent pathway operates predominantly in the cerebellum and the kidney. Our study reveals that administration of D-cysteine protects primary cultures of cerebellar neurons from oxidative stress induced by hydrogen peroxide and attenuates ischaemia-reperfusion injury in the kidney more than L-cysteine. This study presents a novel pathway of hydrogen sulphide production and provides a new therapeutic approach to deliver hydrogen sulphide to specific tissues.
authors: Department of Molecular Pharmacology, National Institute of Neuroscience, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors: Norihiro
authors: N
authors: Shibuya
authors: Shin
authors: S
authors: Koike
authors: Makiko
authors: M
authors: Tanaka
authors: Mari
authors: M
authors: Ishigami-Yuasa
authors: Yuka
authors: Y
authors: Kimura
authors: Yuki
authors: Y
authors: Ogasawara
authors: Kiyoshi
authors: K
authors: Fukui
authors: Noriyuki
authors: N
authors: Nagahara
authors: Hideo
authors: H
authors: Kimura
mesh_terms: D000818:Animals; D053898:Biosynthetic Pathways / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D003545:Cysteine / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects; D003605:D-Amino-Acid Oxidase / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008297:Male; D008322:Mammals / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009928:Organ Specificity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D015427:Reperfusion Injury / Q000473:pathology; D013379:Substrate Specificity / Q000187:drug effects; D013466:Sulfurtransferases / Q000378:metabolism
chemical_list: D003605:D-Amino-Acid Oxidase; D013466:Sulfurtransferases; C021550:3-mercaptopyruvate sulphurtransferase; D003545:Cysteine; D006862:Hydrogen Sulfide