S9-2 Mercaptopyruvate sulfurtransferase and hydrogen sulfide

Hydrogen persulfide (HP) generation is catalyzed by three enzymes: cystathionine β-synthase, cystathionine γ-lyase (cystathionase), and 3-mercaptopyruvate sulfurtransferase (MST). MST-catalyzed HP production is a three-step reaction. In the first step, a sulfur atom is transferred to a catalytic site cysteine residue to form a persulfide as a reaction intermediate. In the second step, the outer sulfur atom of this persulfide intermediate is transferred to a thiol compound (an acceptor substrate), resulting in the formation of another persulfide through a nucleophilic attack. In the final step, this persulfide is reduced by the substrate and/or a biological reductant such as thioredoxin to release HP. Considering the chemistry of redox reactions, all reactions proceed under physiological conditions. Moreover, HP production is only one of four physiological roles of MST. MST catalyzes cysteine degradation to pyruvate via the mercaptopyruvate pathway, a minor pathway in cysteine catabolism. MST also functions as an antioxidant through redox reactions involving its catalytic site cysteine (cysteine–sulfenate cycle) and an intersubunit disulfide bond (a monomer–dimer equilibrium). Finally, it contributes to the production of sulfur oxides through redox reactions involving the stable persulfide intermediate formed at the catalytic site cysteine.