Biochemistry of Redox-Active Sulphur Compounds in Mammalian Cells and Approaches to Detecting Them

Abstract

The discovery of new classes of regulatory molecules in human and animal metabolism always leads to a large-scale study of their properties in the context of biochemistry, physiology, and pharmacology. About 20 years ago, hydrogen sulfide (H2S) and its derivatives – active sulfur forms (ASFs): persulfides, polysulfides, nitrosothiols, sulfenic acids, etc. – became one of such classes of molecules. The participation of ASFs in a variety of physiological and pathological processes, such as regulation of vascular tone, inflammation, long-term potentialization in the central nervous system, etc., has been shown. Changes in ASF levels or patterns of modification of their targets are associated with a wide range of pathologies: cardiovascular, oncologic, neurodegenerative, and others. For a part of these processes, mechanisms have been studied that involve direct modification of regulatory (NF-κB, Keap1) or effector (GAFD, eNOS, TRPA1) proteins through reactions of cysteine residues and metal-containing centers with APS. The presence of different regulated enzymatic systems producing APS and numerous molecular targets allows us to consider H2S and its derivatives as an important class of small regulatory molecules. H2S is counted among the so-called “gas transmitters”, along with nitric oxide(II) and carbon monoxide. Over the last 20 years, a huge amount of data on the biochemistry of these compounds and approaches to their study has been accumulated.