Hydrogen Sulfide Biochemistry and Interplay with Other Gaseous Mediators in Mammalian Physiology

Figure 3

Reaction mechanism of H₂S production by 3-mercaptopyruvate sulfurtransferase (MST). Chemical structure of the metabolites and reaction schemes involved in H₂S synthesis by MST. (a) Production of 3-mercaptopyruvate (3-MP) is catalyzed by cysteine aminotransferase (CAT), with α-ketoglutarate as cosubstrate. (b) MST reaction with its activating substrate 3-MP and acceptor substrates. Upon reacting with 3-MP, the side-chain sulfhydryl of Cys₂₄₈ (CysSH) becomes persulfidated (CysSSH), which activates MST (MST) towards the reaction with the acceptor substrates. The reaction with low-molecular-weight (LMW) thiol-containing substrates (RSH) involves the sequential reaction with two substrate molecules. In the first step, MST transfers the sulfane sulfur from the cysteine persulfide to the RSH, regenerating the enzyme and releasing a persulfide RSSH product. In the second step, another RSH reacts with RSSH to yield H₂S and oxidized RSSR. The reaction of MST with reduced thioredoxin (Trx) proceeds similarly to that with LMW RSH molecules. The MST cysteine persulfide is initially transferred to Trx, yielding CysSSH, which is then attacked by a nearby cysteine thiol, releasing H₂S and yielding oxidized Trx. Chemical structures labeled as α-ketoglutarate, 3-mercaptopyruvate, and L-glutamate are represented as α-ketoglutaric, 3-mercaptopyruvic, and L-glutamic acids, respectively.

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