SIGNIFICANCE

Redox regulates 3-mercaptopyruvate sulfurtransferase (MST, EC 2.8.1.2) activity via both intermolecular and intramolecular redox-sensing switches. The intermolecular switch comprises an intermolecular disulfide bond that forms a homodimer. On the other hand, the intramolecular switch is a catalytic site cysteine that forms a low redox potential sulfenate. Both switches are reduced by thioredoxin with the reducing system, including thioredoxin reductase and NADPH, and to a much lesser extent by reduced glutathione. It becomes clear that MST serves as not only an enzyme in cysteine catabolism, but also as an antioxidant protein.

RECENT ADVANCES

New findings have been accumulated that, in the catalytic process of MST, hydrogen peroxide is possibly produced by persulfide of the sulfur-accepted substrate and sulfur oxides are possibly produced in the redox cycle of persulfide formed at the catalytic site cysteine of the reaction intermediate. Further, we recently succeeded to produce MST knockout (KO) mice.

CRITICAL ISSUES

A congenital metabolic disorder, mercaptolactate-cysteine disulfiduria (MCDU) is caused by MST defect with or without mental retardation. The MST KO mouse is just a MCDU model. Recent findings suggest that hydrogen sulfide and/or sulfur oxides are involved in the neurobehavioral changes in MCDU.

FUTURE DIRECTIONS

We investigate the pathogenesis of MCDU by performing a comprehensive analysis of the MST KO mice to clarify the functional diversity of MST and biological importance of hydrogen sulfide and sulfur oxides in the brain.