Redox regulation of mammalian 3-mercaptopyruvate sulfurtransferase.

A cystine-catabolizing enzyme, 3-mercaptopyruvate sulfurtransferase catalyzes the trans-sulfuration reaction of mercaptopyruvate or thiosulfate to thiol-containing compounds or cyanide. During the catalytic process, persulfide is formed at the catalytic site cysteine residue and a sulfur-acceptor substrate donates the outer sulfur of the persulfide to form a new persulfide molecule. Subsequently, the molecule can be reduced by thioredoxin to form hydrogen sulfide. The enzyme is regulated by redox changes via two redox-sensing molecular switches consisting redox-sensitive cysteine residues. One switch is the catalytic cysteine in itself, which is oxidized to form a cysteine-sulfenate resulting in inhibition of catalytic activity. The sulfenate can be reduced by thioredoxin resulting in restoration of the activity. The redox potential of sulfenate is lower than that of glutathione and greater than that of thioredoxin. The other switch involves cysteine residues positioned on the surface of the enzyme. The oxidation the intermolecular disulfide linkage at these cysteine residues, leading to dimer formation, inhibits enzyme activity. On the other hand, reduction-associated monomer formation increases catalytic activity. Thioredoxin reduces the disulfide bond more effectively than dithiothreitol, although the specificity mechanism has not been identified. Congenital defects in this enzyme result in, mercaptolactate-cysteine disulfiduria associated with or without mental retardation. However, the pathogenesis has not been identified. Because 3-mercaptopyruvate sulfurtransferase serves as a cellular antioxidative protein, the other biological functions related to the inhabitant disease are being investigated.