Nitric oxide synthase reaction catalyzed

Endogenous NO is produced almost exclusively by L-arginine catabolism to L-citrul-line in a reaction catalyzed by a family of nitric oxide synthases (NOSs) [3]. In the first step, Arg is hydroxylated to an enzyme-bound intermediate "-hydroxy-1.-arginine (NHA), and 1 mol of NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) and O2 are consumed. In the second step, N H A is oxidized to citrulline and NO, with consumption of 0.5 mol of NADPH and 1 mol of 02 (Scheme 1.1). Oxygen activation in both steps is carried out by the enzyme-bound heme, which derives electrons from NADPH. Mammalian NOS consists of an N-terminal oxy-... 

Rusche, K. M., Spiering, M. M., Marletta, M. A., Reactions catalyzed by tetrahydrobiopterin-free nitric oxide synthase, Biochemistry VI (1998),... 

A less common reactive species is the Fe peroxo anion expected from two-electron reduction of O2 at a hemoprotein iron atom (Fig. 14, structure A). Protonation of this intermediate would yield the Fe —OOH precursor (Fig. 14, structure B) of the ferryl species. However, it is now clear that the Fe peroxo anion can directly react as a nucleophile with highly electrophilic substrates such as aldehydes. Addition of the peroxo anion to the aldehyde, followed by homolytic scission of the dioxygen bond, is now accepted as the mechanism for the carbon-carbon bond cleavage reactions catalyzed by several cytochrome P450 enzymes, including aromatase, lanosterol 14-demethylase, and sterol 17-lyase (133). A similar nucleophilic addition of the Fe peroxo anion to a carbon-nitrogen double bond has been invoked in the mechanism of the nitric oxide synthases (133). 

Nitric oxide is synthesized from arginine in an NADPH-dependent reaction catalyzed by nitric oxide synthase (Fig. 22-31), a dimeric enzyme structurally related to NADPH cytochrome P-450 reductase (see Box 21-1). The reaction is a five-electron oxidation. Each subunit of the enzyme contains one bound molecule of each of four different cofactors FMN, FAD, tetrahydro-... 

As shown in Figure 10.11, the reaction catalyzed by nitric oxide synthase is hydroxylation of arginine AT-hydroxy-arginine then decomposes to citrulline and nitric oxide. It is unclear whether the immediate product of the enzyme is nitric oxide itself or the nitroxyl anion NO the addition of superoxide dis-mutase in vitro increases the formation of nitric oxide, but this could be the... 

Oxidation of L-arginine by a strain of Nocardia sp. produces nitric oxide and L-citrulline (Chen and Rosazza 1995). The enzyme (nitric oxide synthase) carries out two distinct reactions (1) hydroxylation of L-arginine catalyzed by an enzyme analogous to cytochrome P-450 and (2) a one-electron oxidation of Na -hydroxy-L-arginine to NO and L-citrulline. 

The amino acid Arginine is a precursor to a novel second messenger and neurotransmitter, which is a gas, nitric oxide. Nitric oxide is produced from arginine in an unusual five-electron oxidation that also yields citrulline (see Figure 21.3). The enzyme catalyzing the reaction, nitric oxide synthase, contains bound FMN, FAD, non-heme iron, and tetrahydrobiopterin. 

The complex conversion of arginine to citrulline and nitric oxide is shown in Figure 21.3. The enzyme catalyzing the reaction is nitric oxide synthase. 

The heme-containing metalloenzymes cytochrome P450, chloroperoxidase (CPO) nitric oxide synthase (NOS) , and their relatives catalyze a host of crucial biological oxidation reactions. Highly specific P450s are involved in the selective oxygenations of steroid and prostaglandin biosynthesis. Myeloperoxidase, which is a CPO, is an... 

Hurshman, A.R. and M.A. Marietta (2002). Reactions catalyzed by the heme domain of inducible nitric oxide synthase Evidence for the involvement of tetrahydrobiopterin in electron transfer. Biochemistry 41, 3439-3456. 

Mayer, B., Heinzel, B.. Klatt, P., John M., Schmidt, K., and Bohme, E. (1992). Nitric oxide synthase-catalyzed activation of oxygen and reduction of cytochromes Reaction mechanisms and possible physiological implications. J. Cardiovasc. Pharmacol. 20, S54-S56. 

Fig. 6.15 The role of TxtE in synthesis of the phytotoxin thaxtomin. The P450 TxtE (CYP1048A1) catalyzes the C4 nitration ofl-tryptophan to produce 4-nitrotryptophan (indicated by an arrow). The NO required is generated by a nitric oxide synthase (NOS) enzyme (TxtD) encoded adjacent to txtE on the S. turgidiscabies genome. 4-nitro-tryptophan undergoes a condensation reaction withi-phe-...

Another medically important enzyme, nitric oxide synthase (NOS), has many similarities to cyts P450 and catalyzes the formation of nitric oxide. Nittic oxide is a messenger involved in vasodilation and inflammatory response. The production of nitric oxide is a result of the degradation of the amino acid arginine. Like cytochrome P450, the active center is a heme and the reaction is NAD(P)H dependent. Unlike cytochrome P450s, the current view on the mechanism of NO production does not involve por+Fe =0. Instead, the reactive species is believed to be porFe —00 . NOS is mediated by Ca +-calmodulin and does not produce nitric oxide in the absence of calcium. 

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]. 

Nitric Oxide (NO) Nitric oxide is a relatively stable free radical synthesized from molecular oxygen and the guanidino nitrogen of arginine (see Fig. 22-31) in a reaction catalyzed by NO synthase. 

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