Multiple role of 3‐mercaptopyruvate sulfurtransferase: antioxidative function, H2S and polysulfide production and possible SOx production. (11th January 2018)

• Record Type: Journal Article
• Authors: Nagahara, Noriyuki
• Is Part Of: British journal of pharmacology. Volume 175:Number 4(2018)
• Page Start: 577
• Page End: 589
• Publication Date: 2018-01-11
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.14100
• Languages: English
• ISSNs: 0007-1188

Abstract

Abstract : Rat 3‐mercaptopyruvate sulfurtransferase (MPST) is a 32 808 Da simple protein. Cys 247 is a catalytic site, and Cys 154 and Cys 263 are on the enzyme surface. MPST is found in all tissues, particularly in the kidneys, although the localization of its activity differs in each tissue. In this review, four functions of MPST are reviewed: (i) antioxidative function: Cys 247 is redox‐sensitive and serves as a redox‐sensing switch. It is oxidized to cysteine sulfenate, which has a low redox potential, upon which the enzyme is inactivated. Then, reduced thioredoxin (Trx) with a reducing system (Trx reductase and NADPH) reduces the sulfenate to restore activity; meanwhile, Cys 154 and Cys 263 form an intermolecular disulfide bond, which serves as another redox‐sensing switch. Consequently, Trx specifically cleaves the intermolecular disulfide bond by converting it from the inactive form (dimer) to the active form (monomer). (ii) Hydrogen sulfide and polysulfide production: hydrogen sulfide is produced via reduction of the persulfurated sulfur‐acceptor substrate by reduced Trx or Trx with a reducing system; as an alternative process, stable polysulfurated or persulfurated Cys 247 as a reaction intermediate is reduced by Trx with a reducing system to release hydrogen sulfide and polysulfides. (iii) Possible sulfur oxide production: sulfur oxides (SO, SO2 and SO3 ) can be produced in the redox cycle of sulfane sulfur formed at the catalytic site Cys 247 (Cys–SO −, Cys–SO 2− and Cys–SO 3− ) as reaction intermediates and released by reduced Trx or Trx with a reducing system. (iv) Possible anxiolytic‐like effects: MPST‐knockout mice exhibited anxiolytic‐like effects.