Nitric oxide, cytochrome c oxidase and myoglobin: Competition and reaction pathways

Abstract

It is relevant to cell physiology that nitric oxide (NO) reacts with both cytochrome oxidase (CcOX) and oxygenated myoglobin (MbO 2 ). In this respect, it has been proposed [Pearce, L.L., et al. (2002)

Reproducing kernel potential energy surfaces in biomolecular simulations: Nitric oxide binding to myoglobin

“…These values are in good agreement with the experimentally determined structures with nitric oxide bound to the heme-Fe, including myoglobin, 62-64 indoleamine 2,3-dioxygenase, 65 cytochrome c oxidase, 66 and others (see Table II). The differences might be explained by the effects of the crystal field and the specific structure and electrostatic environment of the distal pocket.…”

Nitric Oxide Binds to the Proximal Heme Coordination Site of the Ferrocytochrome c/Cardiolipin Complex

“…c/CL complex with an excess of oxyhemoglobin, using the method described by Sarti et al (25). The simultaneous formation of met hemoglobin and ferric cyt.…”

Nitric oxide inhibition of respiration involves both competitive (heme) and noncompetitive (copper) binding to cytochromecoxidase

“…However, in 1994 it was additionally shown that mitochondrial oxygen consumption by cytochrome c oxidase (CCO) is reversibly inhibited by NO in a manner apparently competitive with the oxygen tension (4)(5)(6). Inhibition of mitochondrial respiration by NO at CCO has since been implicated in a wide range of physiological processes (7)(8)(9)(10)(11)(12), and several of these require a competitive (with respect to oxygen) element to the interaction, e.g., activating hypoxia-inducible factor (13); maintaining flow-metabolism coupling in the brain (14); and allowing cells distant from capillaries to maintain adequate oxygenation (15). Under pathological conditions such as sepsis, the elevated NO concentration, generated by inducible NO synthase, is associated with mitochondrial dysfunction and is implicated in mortality in the critically ill (16).…”

“…30 and 31). This promiscuity has led to a number of hypotheses proposing that these alternative interactions are physiologically relevant (12,32).…”

“…30 and 31). This promiscuity has led to a number of hypotheses proposing that these alternative interactions are physiologically relevant (12,32).Only one NO molecule per binuclear center should be needed to inhibit competitively with oxygen (6), and both the (oxidized or reduced) mammalian enzyme (33) and reduced bacterial enzyme (34) bind NO with a 1:1 stoichiometry. But flash photolysis and molecular dynamics energy minimization studies have suggested that two NO molecules can be accommodated at the fully reduced binuclear center of Paracoccus denitrificans CCO (35,36); two NO molecules were also reported to bind simultaneously to the homologous heme:copper active site of the Escherichia coli quinol bo 3 oxidase (ref.…”