Chemical regulation of nitric oxide: a role for intracellular myoglobin?
The detailed chemistry of nitric oxide (*NO) and regulation of this potent signal molecule through interactions with cellular components are complex and not clearly understood. In the vasculature, *NO plays a crucial role in vessel dilation by activating soluble guanylyl cyclase (sGC) in vascular smooth muscle cells (VSMC). *NO is responsible for maintaining coronary blood flow and normal cardiac function. However, *NO is a highly reactive molecule and this reactivity toward a range of alternate substrates may interfere with the activation of its preferred molecular target within VSMC. Interestingly, marked changes to *NO homeostasis are linked to disease progression. Thus, the physiological concentration of *NO is carefully regulated. Myoglobin is a haem-containing protein that is present in relatively high concentration in cardiac and skeletal muscle. Recently, the presence of myoglobin has been confirmed in human smooth muscle. The role of intracellular myoglobin is generally accepted as that of a passive di-oxygen storage protein. However, oxygenated myoglobin readily reacts with *NO to yield higher order N-oxides such as nitrate, while both the ferrous and ferric forms of the protein form a stable complex with *NO. Together, these two reactions effectively eliminate *NO on the physiological time-scale and strongly support the idea that myoglobin plays a role in maintaining *NO homeostasis in tissues that contain the protein. Interestingly, human myoglobin contains a sulfhydryl group and forms an S-nitroso-adduct similar to haemoglobin. In this article we discuss the potential for human myoglobin to actively participate in the regulation of *NO by three distinct mechanisms, namely oxidation, ligand binding, and through formation of biologically active S-nitroso-myoglobin.
Centre for Thrombosis and Vascular Research, University of New South Wales, Sydney, New South Wales 2052, Australia.
Emile
E
Andriambeloson
Paul K
PK
Witting
D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009211:Myoglobin / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology
D009211:Myoglobin; D009569:Nitric Oxide; D006162:Guanylate Cyclase