LAUSR

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.