Nitric catalytic cycle

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. 

In the late 1960s, direct observations of substantial amounts (3ppb) of nitric acid vapor in the stratosphere were reported. Crutzen [118] reasoned that if HN03 vapor is present in the stratosphere, it could be broken down to a degree to the active oxides of nitrogen NO (NO and N02) and that these oxides could form a catalytic cycle (or the destruction of the ozone). Johnston and Whitten [119] first realized that if this were so, then supersonic aircraft flying in the stratosphere could wreak harm to the ozone balance in the stratosphere. Much of what appears in this section is drawn from an excellent review by Johnston and Whitten [119]. The most pertinent of the possible NO reactions in the atmosphere are... 

Reactions 2-6 through 2-8 form a catalytic cycle, in that the hydroxyl radical that is used in Reaction 2-6 is r enerated in Reaction 2-8. The net results of this cycle are the oxidations of nitric oxide to nitrogen dioxide and carbon monoxide to carbon dioxide by the oxygen present in the air. 

The reaction of nitric oxide with superoxide dismutase is a simple reversible equilibrium, whereas the catalytic cycle with superoxide involves a two step sequence. Consequently, superoxide dismutase may be reduced by superoxide and then react with nitric oxide to form nitroxyl anion. Nitroxyl anion may react with molecular oxygen to form peroxynitrite anion (ONOO"). 

Minor species observed in the stratosphere are shown in Fig. VIII-11. Of these it is now believed that nitric oxide is the most effective agent to destroy ozone by a catalytic cycle... 

NOS is an important signaling enzyme that synthesizes L-citrulline and nitric oxide (NO) from L-arginine and O2 via two turnovers in a P450-like catalytic cycle (Scheme 2). NOS participates in physiological processes such as neurotransmission, vasodilation, and immune response [54,55]. Improper regulation of NO production can lead to diseases such as septic shock, heart disease, arthritis, and diabetes. 

As shown in Table 3, nitrate anions consxuned in the rate controlling step are reformed in the next step involving nitric radicals and S(IV). This is a sort of a catalytic cycle, where... 

The bacterial, iron-containing cd nitrite reductases constitute another family of enzymes catalyzing the one-electron reduction of nitrite to nitric oxide (74). These enzymes are homodimers of 60-kDa subunits, each containing one heme-c and one heme-rii. Extensive studies have established heme-c as the electron entry site, whereas heme-dj is the catalytic center where nitrite is reduced (95). Three-dimensional structures of two different cytochromes cd have been determined in oxidized and reduced states P. pantotrophus, Pp-NiR (96, 97) and P. aeruginosa, Pa-NiR (98, 99). In both enzymes, heme-c is covalently linked to the A-terminal a-helical domain and heme-di is bound noncovalently to the C-terminal B-propeller domain (Fig. 17). Intramolecular ET between c and di hemes is an essential step in the catalytic cycle this reaction has been studied by several groups using different methods (95, 100-106). The rate constants for Pa-NiR are on the order of 1 s (95, 100-102, 104), while intramolecular ET in Pp-NiR is significantly faster (rate constant of... 

As shown in Scheme 1, NHase catalyzes the conversion of nitriles to amides 4), The active site contains either a non-corrin cobalt(III) or non-heme iron(III). Amino acid sequence comparisons have shown that the primary coordination sphere is conserved regardless of the identity of the metal center and consists of a -C-S-L-C-S-C- motif (5). EPR studies on Fe-NHase revealed the iron center maintains a low-spin Fe(III) state throughout the catalytic cycle, and that the iron center has a variable coordination site for substrate interaction (6). These findings are consistent with the hypothesis that the enzyme functions solely as a hydrolytic (i.e., redox-inactive) catalyst. Incubation of the enzyme with nitric oxide in the dark inactivates the enzyme. Exposure to light was found to reinstate activity with concomitant loss of NO, thus revealing a novel photo-regulatory mechanism (7-70). 

A bacterial flavohemoglobin, which contains a globin domain fused to a flavin/NADH binding domain, functions enzymatically as a nitric oxide dioxygenase, using a catalytic cycle similar to that in Figure 10. The role of this enzyme is apparently to detoxify nitric oxide produced by the body in response to bacterial infection. The distal pocket of flavohemoglobins more closely... 

In the biochemical context, it has been well noted that the chemistry of NO (and of its conjugated acid, FINO (i8)) is quite distinct from that of NO (22). Its occurrence in catalytic cycles of NO synthase, nitrite reductase, and nitric oxide reductase (NOR) has been postulated (23). For example, in the multi-iron containing enzyme NOR two NO molecules are converted reductively to nitrous oxide, N2O, with nitroxyl (NO ), and hyponitrite (N202 ) (24) as putative intermediates (23). 

Topsoe N-Y, Dumesic JA, Tops0e H (1995) Vanadia-Titania Catalysts for Selective Catalytic Reduction of Nitric-Oxide by Ammonia. 2. Studies of Active-Sites and Formulation of Catalytic Cycles. J Catal 151 (l) 241-252... 

Tops0e, N.-Y., Dumesic, J.A., and Tops0e, H. Vanadia/titania catalysts for selective catalytic reduction of nitric oxide by ammonia. II. Studies of active sites and formulation of catalytic cycles. J. Catal. 1995,151, 241-252. 

Reactions of this type can be sequentially incorporated into catalytic cycles. An example of such a cycle is shown in Scheme 9.4, where triphenylphosphine is oxidized to triphenylphosphine oxide by reaction with Mn (porph)0, and the nitrite complex Mn (porph)N02 then photoreacts to give Mn (porph)0 and nitric oxideS Photooxidations using Mn(TPP)(OAc) and periodate ion also involve... 

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