Nitric oxide enzyme reactions

Chemiluminescence. Chemiluminescence (262—265) is the emission of light duting an exothermic chemical reaction, generaUy as fluorescence. It often occurs ia oxidation processes, and enzyme-mediated bioluminescence has important analytical appHcations (241,262). Chemiluminescence analysis is highly specific and can reach ppb detection limits with relatively simple iastmmentation. Nitric oxide has been so analyzed from reaction with ozone (266—268), and ozone can be detected by the emission at 585 nm from reaction with ethylene. 

In contrast to superoxide, which participates in one-electron transfer reactions as a reductant, nitric oxide is apparently able to oxidize various transition metal-containing proteins and enzymes. The study of NO reaction with hemoglobin has been started many years ago when... 

In this chapter the generation of free radicals, mainly superoxide and nitric oxide, catalyzed by prooxidant enzymes will be considered. Enzymes are apparently able to produce some other free radicals (for example, HO and N02), although their formation is not always rigorously proved or verified. The reactions of such enzymes as lipoxygenase and cyclooxygenase also proceed by free radical mechanism, but the free radicals formed are consumed in their catalytic cycles and probably not to be released outside. Therefore, these enzymes are considered separately in Chapter 26 dedicated to enzymatic lipid peroxidation. 

Simultaneous generation of nitric oxide and superoxide by NO synthases results in the formation of peroxynitrite. As the reaction between these free radicals proceeds with a diffusion-controlled rate (Chapter 21), it is surprising that it is possible to detect experimentally both superoxide and NO during NO synthase catalysis. However, Pou et al. [147] pointed out that the reason is the fact that superoxide and nitric oxide are generated consecutively at the same heme iron site. Therefore, after superoxide production NO synthase must cycle twice before NO production. Correspondingly, there is enough time for superoxide to diffuse from the enzyme and react with other biomolecules. 

S / V CONTENTS Preface, Robert W. Hay. Structure and Function of Manganese-Containing Biomolecules, David C. Weather-bum. Repertories of Metal Ions as Lewis Acid Catalysts in Organic Reactions, Junghan Suh. The Multicopper-Enzyme Ascorbate Oxidase, Albrecht Messerschmidt. The Bioinorganic Chemistry of Aluminum, Tomas Kiss and Etelka Farkas. The Role of Nitric Oxide in Animal Physiology, Anthony R. Butler, Frederick Flitney and Peter Rhodes. Index. 

The NO/NO+ and NO/NO- self-exchange rates are quite slow (42). Therefore, the kinetics of nitric oxide electron transfer reactions are strongly affected by transition metal complexes, particularly by those that are labile and redox active which can serve to promote these reactions. Although iron is the most important metal target for nitric oxide in mammalian biology, other metal centers might also react with NO. For example, both cobalt (in the form of cobalamin) (43,44) and copper (in the form of different types of copper proteins) (45) have been identified as potential NO targets. In addition, a substantial fraction of the bacterial nitrite reductases (which catalyze reduction of NO2 to NO) are copper enzymes (46). The interactions of NO with such metal centers continue to be rich for further exploration. 

Redox reactions involving nitric oxide have important implications beyond their fundamental chemistry as demonstrated by the controversy in the biomedical literature regarding conditions under which generation of NO leads to the amelioration or the exacerbation of oxidative stress in mammalian systems (95). Oxidative stress is defined as a disturbance in the balance between production of reactive oxygen species (pro-oxidants) and antioxidant defenses (96). Reactive oxygen species include free radicals and peroxides as well as other reactants such as oxidative enzymes with metal ion sites in high oxidation states. The... 

Nitric oxide and nitrite react with other peroxidase enzymes such as horseradish peroxidase (HRP) (138a,139), lactoperoxidase (138a) and eosinophil peroxidase (140) similarly. The rate constants for reaction of NO with compounds I and II in HRP were found to be 7.0 x 105M 1s 1 and 1.3 x 106M 1s 1, respectively (139). Catalytic consumption of NO as measured by an NO sensitive electrode in the presence of HRP compounds I and II is shown in Fig. 5 where accelerated consumption of NO is achieved even in deoxygenated solutions (140). 

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-... 

Despite intense study of the chemical reactivity of the inorganic NO donor SNP with a number of electrophiles and nucleophiles (in particular thiols), the mechanism of NO release from this drug also remains incompletely understood. In biological systems, both enzymatic and non-enzymatic pathways appear to be involved [28]. Nitric oxide release is thought to be preceded by a one-electron reduction step followed by release of cyanide, and an inner-sphere charge transfer reaction between the ni-trosonium ion (NO+) and the ferrous iron (Fe2+). Upon addition of SNP to tissues, formation of iron nitrosyl complexes, which are in equilibrium with S-nitrosothiols, has been observed. A membrane-bound enzyme may be involved in the generation of NO from SNP in vascular tissue [35], but the exact nature of this reducing activity is unknown. 

The role of arginase in some cells is not to produce urea but to regulate the concentration of arginine. This is important since arginine is the substrate for the reaction that produces an important messenger molecule, nitric oxide, via the enzyme nitric oxide synthase. 

---