title: Understanding the mechanism of action of cytochrome c oxidase in normal and disease states: shark heart enzyme, a potential model.
abstract: Cytochrome c oxidase, the final member of the electron transport chain, is crucial to respiration and also contributes to the synthesis of cellular ATP. The total absence of this enzyme is incompatible with life and its deficiency or malfunction leads to a number of serious disease states. Understanding the mechanism of action of this enzyme, which is an important prerequisite to unravelling its role in the pathogenesis of disease states, is hampered by the lack of suitable enzyme models. The bovine enzyme, which is commonly used, is enormously complex and the bacterial enzymes, which are structurally simple, appear to follow a different mechanism of action. The hammer head shark is a seasonal resident of the warm waters of the Caribbean Sea. The work presented here indicates that, like the bovine enzyme, the enzyme of the heart of this shark (i) possesses thirteen subunits and two substrate binding sites and (ii) exhibits biphasic kinetics. The work also confirms that, unlike the bovine enzyme which is dimeric, the shark enzyme functions as a monomer. Given this latter simplifying feature, in conjunction with its kinetic and structural similarities to the more complex mammalian varieties, we propose that shark heart cytochrome c oxidase replace the bovine and bacterial forms as the enzyme of choice for model studies.
authors.affiliation: Department of Preclinical Sciences, University of the West Indies, St Augustine, Trinidad and Tobago.
authors.forename: A
authors.initials: A
authors.lastname: Lalla
authors.forename: T
authors.initials: T
authors.lastname: Alleyne
authors.forename: Y
authors.initials: Y
authors.lastname: Andrews
mesh_terms: D000818:Animals; D002417:Cattle; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D009206:Myocardium / Q000201:enzymology; D012754:Sharks
chemical_list: D003576:Electron Transport Complex IV