Catalytic promiscuity and heme-dependent redox regulation of H 2 S 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.

Regulators of the transsulfuration pathway

“…When haem is bound by endogenous ligands, the production of cystathionine occurs due to the higher intracellular levels of serine and its greater affinity for CBS as compared to cysteine. Similarly, the affinity of cystathionine for CSE is greater than that of cysteine, favouring the generation of cysteine as opposed to H 2 S. During conditions of stress, when NO or carbon monoxide (CO) levels rise, causing inhibition of CBS due to the formation of nitrosyl or ferrous carbonyl CBS, homocysteine accumulates, leading to the production of H 2 S by CSE (Banerjee, ). Enzymes which catabolize cysteine also have an effect on the production of H 2 S.…”

Homeostatic impact of sulfite and hydrogen sulfide on cysteine catabolism

“…Cysteine is a semi‐essential amino acid, as it can either be obtained from the diet or enzymatically produced from methionine via the transsulfuration pathway (Figure ) (Zou and Banerjee, ; Banerjee, ). Methionine functions as an important methyl group donor in the cell following its conversion to S‐adenosylmethionine.…”

Hemoglobin: A New Biocatalyst for the Synthesis of 2‐substituted Benzoxazoles via Oxidative Cyclization

“…[11] Mining for new types of organic reactions that can be catalyzed by proteins has drawn much attention in recent years and has dramatically expanded the application of proteins within the field of organic chemistry. [12][13][14][15][16][17][18] Hemoproteins are promising biocatalysts for synthetic applications that incorporate oxidative reactions (hydroxylation, epoxidation, and sulfoxidation) and carbene-mediated transformations (olefin cyclopropanation, carbene insertion, and aldehyde olefination). [19][20][21][22][23][24][25] Hemoglobin, a necessary vehicle for oxygen transport in the body, has been also used in several organic reactions as a stable and abundant biocatalyst, such as lipid peroxidation, aniline hydroxylation, oxidation of hydrogen sulfide and pyrene.…”