PLP-dependent H2S biogenesis

The role of endogenously produced H2S in mediating varied physiological effects in mammals has spurred enormous recent interest in understanding its biology and in exploiting its pharmacological potential. In these early days in the field of H2S signaling, large gaps exist in our understanding of its biological targets, its mechanisms of action and the regulation of its biogenesis and its clearance. Two branches within the sulfur metabolic pathway contribute to H2S production: (i) the reverse transsulfuration pathway in which two pyridoxal 5′-phosphate-dependent (PLP) enzymes, cystathionine β-synthase and cystathionine γ-lyase convert homocysteine successively to cystathionine and cysteine and (ii) a branch of the cysteine catabolic pathway which converts cysteine to mercaptopyruvate via a PLP-dependent cysteine aminotransferase and subsequently, to mercaptopyruvate sulfur transferase-bound persulfide from which H2S can be liberated. In this review, we present an overview of the kinetics of the H2S-generating reactions, compare the structures of the PLP-enzymes involved in its biogenesis and discuss strategies for their regulation.This article is part of a Special Issue entitled: Pyridoxal Phospate Enzymology.

Research highlights► H2S is a gaseous signaling molecule, with neuromodulatory and cardioprotective effects. ► Three of the H2S-producing enzymes are pyridoxal phosphate-dependent and utilize the sulfur amino acids as substrates. ► The structure, function and regulation of the H2S producing enzymes are the focus of this review article.