Interactions of nitric oxide-derived reactive nitrogen species with peroxidases and lipoxygenases.
Nitric oxide (NO) is a major free radical modulator of smooth muscle tone, which under basal conditions acts to preserve vascular homeostasis through its anti-inflammatory properties. The biochemistry of NO, in particular, its rapid conversion in vivo into secondary reactive nitrogen species (RNS), its chemical nature as a free radical and its high diffusibility and hydrophobicity dictate that this species will interact with numerous biomolecules and enzymes. In this review, we consider the interactions of a number of enzymes found in the vasculature with NO and NO-derived RNS. All these enzymes are either homeostatic or promote the development of atherosclerosis and hypertension. Therefore their interactions with NO and NO-derived RNS will be of central importance in the initiation and progression of vascular disease. In some examples, (e.g. lipoxygenase, LOX), such interactions provide catalytic 'sinks' for NO, but for others, in particular peroxidases and prostaglandin H synthase (PGHS), reactions with NO may be detrimental. Nitric oxide and NO-derived RNS directly modulate the activity of vascular peroxidases and LOXs through a combination of effects, including transcriptional regulation, altering substrate availability, and direct reaction with enzyme turnover intermediates. Therefore, these interactions will have two major consequences: (i) depletion of NO levels available to cause vasorelaxation and prevent leukocyte/platelet adhesion and (ii) modulation of activity of the target enzymes, thereby altering the generation of bioactive signaling molecules involved in maintenance of vascular homeostasis, including prostaglandins and leukotrienes.
Coffey
M J
MJ
Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff, Wales CF14 4XN, United Kingdom.
Coles
B
B
O'Donnell
V B
VB
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010544:Peroxidases / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D014652:Vascular Diseases / Q000209:etiology / Q000378:metabolism
D026361:Reactive Nitrogen Species; D009569:Nitric Oxide; D010544:Peroxidases; D005979:Glutathione Peroxidase; D008084:Lipoxygenase; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D011451:Prostaglandin-Endoperoxide Synthases