Nitric oxide synthesis mammalian

The gas nitric oxide (NO) was first identified as a putative neurotransmitter substance in the mammalian brain by Garthwaite et al. in 1988 (1). In 1990, the enzyme responsible for synthesis of NO in the brain, NO synthase (NOS), was purified and antibodies to it were used to establish the distribution of NO-producing neurons in the rat brain (2). NOS was also found to be responsible for an enzyme activity in the brain known as NADPH diaphorase that was first described by Thomas and Pearse in 1961 (2—5). 

The chemical biology of nitric oxide (NO) and its derivatives rely heavily on the interaction of this diatom with heme and nonheme iron enzymes. Such interactions are important in the mammalian cardiovascular system as well as in the detoxification of NO in pathogenic microbes. As such, synthetic bioinorganic chemists have designed and constructed a variety of low molecular weight coordination complexes to understand the structural and reactive properties of FeNO systems as they relate to biological processes. Over the last several years, much synthetic work has focused on the construction of FeNO and FeNO complexes as representative models of NO reductase enzymes and as potential nitroxyl- or FINO-releasing molecules for new cardiovascular therapeutics. This review describes the synthesis, structure, spectroscopy, and reactivity of such FeNO systems published from 2011 to 2014. 

Combined immunohistochemical, in situ hybridisation, and biochemical studies provide evidence for nitric oxide synthase synthesis in two cell populations of the anterior pituitary gland, gonadotrophs and folliculo-stellate cells, and for an inhibitory effect of NO on stimulated release of LH (Cec-CATELLi et al. 1993). The folhculo-stellate cells do not produce any known hormones (Horvath and Kovacs 1988) but may indirectly influence growth-hormone secretion. Thioredoxin was prominently localised in the folliculo-stellate cells of the mammalian adenohypophysis while only a minor proportion of the glandular cells were positive (Padilla et al. 1992). Glutaredoxin localisation in the adenohypophysis resembled that of thioredoxin. 

Recent discovery of nitric oxide ( NO), which controls and influences a number of critical physiological processes, as a mammalian metabolic intermediate has stimulated rapid progress of studies on nitric oxide synthase (NOS) [267-269]. The formation of NO from L-arginine in mammalian cells is catalyzed by NOS. The inducible NOS has now been known to contain a cytochrome P-450 type iron-protoporphyrin IX prosthetic group and 1 equiv each of FAD and FMN per subunit [270, 271]. Further, NOS requires NADPH to proceed the reactions. Interestingly, P-450 itself has been demonstrated to catalyze NO synthesis [272, 273]. While the detail of the reaction mechanism is still obscure. Scheme 17 summarizes proposed reaction sequences [269]. 

Marietta, M.A. (1988). Mammalian synthesis of nitrite, nitrate, nitric oxide and N-nitrosating agents. Chem. Res. Toxicol. 1,249-257. 

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