Carbamate kinase (CK)

Carbamate kinase (EC 2.7.2.2) is an enzyme that plays a pivotal role in the energy metabolism of various anaerobic microorganisms, including bacteria and protozoan parasites such as Giardia lamblia and Trichomonas vaginalis. It catalyzes the reversible conversion of carbamoyl phosphate and ADP to ATP and carbamate, serving as the final step in the arginine deiminase (ADI) pathway. This pathway is a major source of ATP for these organisms under anaerobic conditions, where they lack a traditional respiratory chain. Crucially, carbamate kinase is absent in humans and other higher eukaryotes, which utilize the distinct carbamoyl phosphate synthetase (CPS) for similar metabolic needs, making it an attractive and highly selective target for antimicrobial and antiparasitic drug development. Inhibition of the enzyme leads to the depletion of cellular ATP and subsequent death of the pathogen. Research has identified the FDA-approved drug disulfiram as a potent covalent inhibitor of the Giardia enzyme, offering a potential path for drug repurposing to treat metronidazole-resistant infections.

Other names

Carbamoyl phosphokinaseATP:carbamate phosphotransferaseCatabolic carbamate kinasearcCCarbamate kinase 1

Covalent inhibition of the enzyme's active site (specifically thiocarbamoylation of a conserved cysteine residue, such as Cys-242 in Giardia lamblia), which prevents the binding of ADP/ATP and halts energy production in the pathogen.