Catalytic promiscuity and heme-dependent redox regulation of H2S synthesis

Abstract

The view of enzymes as punctilious catalysts has been shifting as examples of their promiscuous behavior increase. However, unlike a number of cases where the physiological relevance of breached substrate specificity is questionable, the very synthesis of H₂S relies on substrate and reaction promiscuity, which presents the enzymes with a multitude of substrate and reaction choices. The transsulfuration pathway, a major source of H₂S, is inherently substrate-ambiguous. A heme-regulated switch embedded in the first enzyme in the pathway can help avert the stochastic production of cysteine versus H₂S and control switching between metabolic tracks to meet cellular needs. This review discusses the dominant role of enzyme promiscuity in pathways that double as sulfur catabolic and H₂S synthetic tracks.