Donors organic nitrites

These compounds contain the fragment R as an alkyl or aryl moiety. In other words, they result from the esterification of an alcohol or a phenol with nitrous acid, nitric acid, phosphoric acid, sulfuric acid, or sulfamic acid, respectively. Many of the esters to be examined in this chapter must be activated prior to eliciting their effects, e.g., the organic nitrites and nitrates, which act as donors of nitric oxide or an analogous molecule, and phosphates, which are activated by hydrolysis or even by phosphorylation (antiviral agents). Sulfates are very seldom active or used as prodrugs, but they have significance as metabolites and as industrial xenobiotics. 

Organic nitrites (amyl nitrite and isobutyl nitrite) cause dizziness, giddiness, rapid heart rate, lowered blood pressure, "speeding," and flushing of the skin. These effects last only a few minutes and can readily be repeated. The main effect of the drug on sexual performance is probably to enhance or prolong erection through the release of nitric oxide in the corpora cavernosa (see Chapter 19 Nitric Oxide, Donors, Inhibitors). 

Tolerance limits the clinical use of organic nitrite and nitrate esters it is associated with increased angiotensin II (ANGII)-dependent vascular production of superoxide radical from NAD(P)H oxidase and endothelial NOS (eNOS) (25,26). The superoxide radical generated by these enzymes reacts with NO derived from the NO-donor to form peroxynitrite, as indicated by the finding of increased urinary 3-nitrotyrosine in nitrate-tolerant patients (27). Importantly, nitrate tolerance is also associated with cross-tolerance to endothelium-derived NO (28), both by... 

In fimgi and similar organisms, reduced pyridine is the apparent physiological electron donor for nitrite reduction. However, the enzyme can also utilize reduced viologen dyes thereby bypassing the flavin portion of the enzyme (see electron transfer scheme on page 136). The metabolic source of the NADPH for nitrite has not been established. 

An important development is the appreciation of the role of anammox bacteria. These carry out the anaerobic reaction between NH4 and NO2 in which nitrite is the electron donor with the production of N2 (Schmid et al. 2005). Several groups of bacteria have been implicated, and all of them belong to the phylum Planctomyces, although quite distinct organisms may be involved. They... 

Nitric oxide generation from L-arginine and nitric oxide donors and the formation of cGMP. L-NMMA inhibits nitric oxide synthase. Some of the nitric oxide donors such as furoxans and organic nitrates and nitrites require a thiol cofactor such as cysteine or glutathione to form nitric oxide. 

Similar mechanisms operate in the action of nitrate reductase and nitrite reductase. Both of these substances are produced from ammonia by oxidation. Plants and soil bacteria can reduce these compounds to provide ammonia for metabolism. The common agricultural fertilizer ammonium nitrate, NH4NO3, provides reduced nitrogen for plant growth directly, and by providing a substrate for nitrate reduction. NADH or NADPH is the electron donor for nitrate reductase, depending on the organism. 

Nitrification must be followed by denitrification to remove nitrogen from wastewater. It implies the reduction of nitrate to nitric oxide, nitrous oxide and nitrogen gas, coupled to the respiratory electron transport chain (because nitrates or nitrites are used as electron acceptors for the oxidation of a variety of organic or inorganic electron donors). 

Nitrite and nitrate are reduced to gaseous nitrogen by a variety of facultative heterotrophs in an anoxic environment. An organic source, such as acetic acid, sewage, acetone, ethanol, methanol, or sugar is needed to act as hydrogen donor (oxygen acceptor) and to supply carbon for synthesis. Methanol is used, as it is frequently the least expensive. The basic reactions take the form ... 

In the heterotrophic nitrate respiration, in most cases hydrogen atoms derived from organic compounds ([H], mostly in the form of NADH in the case of heterotrophic denitriliers) are first oxidized with nitrate. The reaction is catalyzed by nitrate reductase. The enzyme contains Mo, [Fe4S4] and [Fe2S2] clusters (Fe/S), and cytochrome b (Chaudhry and MacGregor, 1983). Mo is present in the enzyme as molybdenum cofactors combining with molybdopterin or molybdopterin guanine dinucleotide. The enzyme catalyzes the reduction of nitrate to nitrite with ubiquinol or menaquinol (QH2) as the electron donor. 

Nitrous acid is used in the well-known preparation of diazonium compounds in organic chemistry. Numerous organic derivatives of the N02 group are known. They are of two types nitrites, R—ONO, and nitro compounds, R—N02. Similar tautomerism occurs in inorganic complexes, in which either oxygen or nitrogen is the actual donor atom when NOj is a ligand. 

The physiological electron donors for NIR are either the cupredoxins pseudoazurin or azurin depending on the organism. Pseudoazurin, for example, reduces the type-1 copper and subsequently the electron is transferred to the type-2 copper site, which is also the binding site for nitrite. Nitrite is bound to the type-2 copper site as demonstrated by electron nucleus double resonance studies on NIR from Achromohacter xylosoxidans and in a crystal structure of the complex between nitrite and NIR from A. cycloclastes The crystal structure of the complex shows that nitrite binds asymmetrically with the oxygens toward the copper. 

---