The dual role of heme as cofactor and substrate in the biosynthesis of carbon monoxide

Abstract

Carbon monoxide (CO) is a ubiquitous molecule in the atmosphere. The metabolism of mammalian, plastidic, and bacterial cells also produces CO as a byproduct of the catalytic cycle of heme degradation carried out by the enzyme heme oxygenase (HO). The biological role of CO spans the range from toxic to cytoprotective, depending on concentration. CO generated by the catalytic activity of HO is now known to function in several important physiological processes, including vasodilation, apoptosis, inflammation, and possibly neurotransmission. Consequently, understanding the details of the reaction that leads to the formation of this important gaseous molecule from heme has become an important aspect in the study of the chemistry and biochemistry of HO, which utilizes heme in the dual capacity of substrate and cofactor. In this chapter, a summary, and when appropriate, discussion of the current understanding of the structural, dynamical, and reactive properties that allow HO to breakdown heme into iron, biliverdin, and CO is presented.