Sulfhydryl enzyme

Sulfhydryl enzymes are a broad functional class of enzymes that require a free thiol (-SH) group, typically from a cysteine residue, for their catalytic activity or to maintain their active tertiary structure [1]. This group includes a wide variety of essential proteins such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), various cysteine proteases like cathepsins, and certain phosphatases [2]. Because the sulfhydryl group is highly nucleophilic, these enzymes are particularly vulnerable to inhibition by heavy metals like mercury, lead, and arsenic, which form stable covalent bonds with the sulfur atom, leading to widespread metabolic disruption [1, 4]. In clinical practice, certain drugs like disulfiram exploit this reactivity by inhibiting specific sulfhydryl-containing enzymes like aldehyde dehydrogenase to treat alcohol use disorder [4]. Proton pump inhibitors like omeprazole also function by forming disulfide bonds with sulfhydryl groups on the H+/K+-ATPase [5]. While specific members of this class are vital therapeutic targets, the term 'sulfhydryl enzymes' refers to a collective biochemical category rather than a single specific drug target [1]. Broad-spectrum interference with these enzymes often results in significant systemic toxicity due to their ubiquity in human physiology [3]. Consequently, drug development focusing on this class requires high specificity to avoid off-target effects on the cellular redox balance and metabolic pathways [2].

Other names

Thiol enzymeCysteine-dependent enzymeSH-enzymeCysteine enzyme

Inhibition occurs through the covalent modification of the nucleophilic sulfhydryl (-SH) group of cysteine residues within the enzyme's active or allosteric sites, often forming mercaptides or disulfide bridges [1, 5].