Nitric oxide synthase is a cytochrome P-450 type hemoprotein.
ABSTRACT Nitric oxide has emerged as an important mammalian metabolic intermediate involved in critical physiological functions such as vasodilation, neuronal transmission, and cytostasis. Nitric oxide synthase (NOS) catalyzes the five-electron oxidation of L-arginine to citrulline and nitric oxide. Cosubstrates for the reaction include molecular oxygen and NADPH. In addition, there is a requirement for tetrahydrobiopterin. NOS also contains the coenzymes FAD and FMN and demonstrates significant amino acid sequence homology to NADPH-cytochrome P-450 reductase. Herein we report the identification of the inducible macrophage NOS as a cytochrome P-450 type hemoprotein. The pyridine hemochrome assay showed that the NOS contained a bound protoporphyrin IX heme. The reduced carbon monoxide binding spectrum shows an absorption maximum at 447 nm indicative of a cytochrome P-450 hemoprotein. A mixture of carbon monoxide and oxygen (80%/20%) potently inhibited the reaction (73-79%), showing that the heme functions directly in the oxidative conversion of L-arginine to nitric oxide and citrulline. Additionally, partially purified NOS from rat cerebellum was inhibited by CO, suggesting that this isoform may also contain a P-450-type heme. NOS is the first example of a soluble cytochrome P-450 in eukaryotes. In addition, the presence of FAD and FMN indicates that this is the first catalytically self-sufficient mammalian P-450 enzyme, containing both a reductase and a heme domain on the same polypeptide.
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ABSTRACT: Background: Metabolic syndrome is a collection of ailments resulting in a higher risk of cardiovascular disease and type II diabetes mellitus. It also results in prolonged endothelial dysfunction which promotes hypertension. Objective: The current study examines the acute effect of carbon monoxide (CO) inhibition and nitric oxide (NO) stimulation in septal coronary arteries. Methods: These studies were conducted in inactin anesthetized obese and lean Zucker rats (13-14 weeks of age). Coronary arteries were isolated from obese and lean Zucker rats and in vitro experiments were conducted. Isolated coronary arteries were pre-treated with chromium mesoporphyrin (CrMP) which is a heme oxygenase inhibitor and L-arginine, a NO precursor. Results: Blood pressure, non-fasting blood glucose, HBCO, CO levels and Arginase I expression were higher in obese Zucker rats (ZR) as compared to the lean (L) group. Obese ZR had higher body, kidney and heart weights as compared to the LZR. Acetylcholine induced vasodilation was greatly attenuated in Obese ZR compared to the lean group. No differences in the diameters of the septal coronary artery were observed in both groups when treated with CrMP. However, pretreatment with L-arginine, abolished the differences between the groups. Conclusion: This study demonstrates the potential of NO induction to improve coronary blood flow during metabolic syndrome induced endothelial dysfunction, where alterations in CO levels appeared to have no significant coronary effects.The International journal of medicine. 03/2014; 2(1):8.
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ABSTRACT: Carbon monoxide was previously considered to just be a toxic gas. A wealth of recent information has, however, shown that it is also an important endogenously produced signalling molecule involved in multiple biological processes. Endogenously produced carbon monoxide may thus play an important role in nociceptive processing and in regulation of cerebral arterial tone. Carbon monoxide-induced headache shares many characteristics with migraine and other headaches. The mechanisms whereby carbon monoxide causes headache may include hypoxia, nitric oxide signalling and activation of cyclic guanosine monophosphate pathways. Here, we review the literature about carbon monoxide-induced headache and its possible mechanisms. We suggest, for the first time, that carbon monoxide may play an important role in the mechanisms of migraine and other headaches.Cephalalgia 05/2014; · 3.49 Impact Factor
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ABSTRACT: Carbon monoxide (CO) is increasingly recognized as a cell-signalling molecule akin to nitric oxide (NO). CO has attracted particular attention as a potential therapeutic agent because of its reported anti-hypertensive, anti-inflammatory and cell-protective effects. We discuss recent progress in identifying new effector systems and elucidating the mechanisms of action of CO on, e.g., ion channels, as well as the design of novel methods to monitor CO in cellular environments. We also report on recent developments in the area of CO-releasing molecules (CORMs) and materials for controlled CO application. Novel triggers for CO release, metal carbonyls and degradation mechanisms of CORMs are highlighted. In addition, potential formulations of CORMs for targeted CO release are discussed.Chemical Communications 02/2014; · 6.38 Impact Factor