S9-1 Sulfurtransferases and their role in hydrogen sulfide generation

Abstract

The rhodanese superfamily (EC 2.8.1.x) includes tandem-domain thiosulfate:cyanide sulfurtransferase (TST, EC 2.8.1.1) and the strictly related 3-mercaptopyruvate:cyanide sulfurtransferase (MPST, EC 2.8.1.2). TST is the key enzyme, in the active center of which the persulfide group is created. The highly reactive sulfane sulfur atom of this group can be transferred to a substrate, e.g., cyanide detoxification, or can be passed to another protein acceptor participating in different cellular processes, e.g., biosynthesis of cofactors or thionucleosides. MPST transfers the sulfur atom from mercaptopyruvate, a product of cysteine transamination, to acceptors, such as cyanide (forming thiocyanate) or sulfite (forming thiosulfate – a sulfane sulfur-containing compound). Several metabolic reactions are known to generate sulfane sulfur in vitro , but their relative importance in vivo is not yet known. Current knowledge about sulfur donors assumes that the primary source of sulfane sulfur in eukaryotic cells relies on l -cysteine desulfuration pathway. Gamma-cystathionase (CTH, EC 4.4.1.1), an enzyme on the pathway, participates in endogenous production of H 2 S from l -cysteine. A product of CTH reaction, thiocystine, has been suggested to serve as the sulfane sulfur donor substrate for rhodanese. The potential role of the sulfane sulfur pool as an H 2 S reservoir and factors influencing the activity of sulfane sulfur-generating enzymes are under debate. The current study demonstrates that the MPST-dependent mitochondrial H 2 S-producing pathway is affected by oxidative stress, what may attenuate the production of H 2 S, and leads to various pathophysiological conditions. The intriguing problem is to identify possible sulfane sulfur donor(s) and/or acceptor(s), and to determine the regulatory role of sulfur in cellular metabolism.