Roles of stress-inducible carbon monoxide in the regulation of liver function

Carbon monoxide (CO) is a gaseous product generated by heme oxygenase (HO). As the liver is a gigantic resource of CO derived from heme degradation in vivo, constitutive and inducible CO has been suggested to regulate porto-sinusoidal vascular as well as biliary function. Previous studies revealed that CO generated by HO modulates function of different heme proteins or enzymes through binding to their prosthetic ferrous heme to regulate the biological function of the hepatobiliary systems; the proteins targeted by the gas involve soluble guanylate cyclase, cytochromes P450 and cystathionine β-synthase. Because of the heterogeneous distribution of these enzymes in the liver tissue, CO regulates liver functions through multiple mechanisms that protect the tissue against varied noxious stimuli. The current article overviews the intriguing regulatory mechanisms operated by CO and their medical implications.