Oxidation aerobic flavin system

The aerobic flavin system with NHzNHzasa reducing agent that was employed for the sulfoxidation (Section 8.2.2.2) can also be used for the N-oxidation of tertiary amines [59]. However the reaction requires elevated temperature (60 °C) (Eq. (8.27)), most likely because elimination of O H from the flavin-OH (cf. 26 17, Scheme 8.4) is difficult for the N,N,N-3,5,10-trialkylated flavin at the higher pH caused by the amine. 

Aerobic respiration can be subdivided into a number of distinct but coupled processes, such as the carbon flow pathways resulting in the production of carbon dioxide and the oxidation of NADH + H+ and FADH2 (flavin adenine dinucleotide) to water via the electron transport systems or the respiratory chain. 

The biochemical importance of flavin coenzymes ap-pears to be their versatility in mediating a variety of redox processes, including electron transfer and the activation of molecular oxygen for oxygenation reactions. An especially important manifestation of their redox versatility is their ability to serve as the switch point from the two-electron processes, which predominate in cytosolic carbon metabo-lism, to the one-electron transfer processes, which predomi-nate in membrane-associated terminal electron-transfer pathways. In mammalian cells, for example, the end products of the aerobic metabolism of glucose are C02 and NADH (see chapter 13). The terminal electron-transfer pathway is a membrane-bound system of cytochromes, nonheme iron proteins, and copper-heme proteins—all one-electron acceptors that transfer electrons ultimately to 02 to produce H20 and NAD+ with the concomitant production of ATP from ADP and P . The interaction of NADH with this pathway is mediated by NADH dehydrogenase, a flavoprotein that couples the two-electron oxidation of NADH with the one-electron reductive processes of the membrane. 

The catalytic activity of the immobilized flavin was determined using the oxidation of an NADH-analog, namely 1-benzyl-1,4-dihydronicotinamide (BNAH), as a model reaction (Figure 8). If a potential of +0.9 V is applied to the system, hydrogen peroxide, which is formed in the aerobic oxidation of BNAH by flavin, can be oxidized... 

The methanotrophic bacteria have one known pathway for aerobic methane oxidation to CO2 31, 42,123). MMO catalyzes the first energetically difficult step in the formation of methanol from methane. The second step is catalyzed by methanol dehydrogenase (with a PQQ cofactor) and results in formation of formaldehyde, which is then converted by formaldehyde dehydrogenase (with no known cofactor) to formate. Finally, carbon dioxide is produced by formate dehydrogenase (with five different iron-sulfur clusters, a Mo-pterin cofactor, and an unusual flavin) 31, 42, 123). MMOs have a unique ability to oxidize a broad range 31,42,128,129) of hydrocarbons in addition to methane. One other system with a similar broad substrate utilization is the monoheme cytochrome P450 family, but in this case different isozymes show different specific activities (31). For soluble MMO, one single... 

The 5-deazaflavin (203), in combination with flavin mononucleotide (FMN), provides an efficient catalytic system for the aerobic oxidation of benzylamines to benzaldehydes (Scheme 90). Alternatively, an auto-... 

The formation of superoxide is the result of one electron transfer by several coenzymes in ETS, including flavins, flavoproteins, quinones, and iron sulfur proteins. This product has a longer half-life than other intermediates and is toxic to anaerobic bacteria. Peroxidase is formed by two electron transfers and mediated by flavoproteins. Peroxidase is further reduced to the hydroxyl radical with the addition of one electron followed by subsequent reduction to water by the addition of another electron. The oxidative effect of these intermediates can result in the destruction of cells. The aerobic bacteria have enzyme systems such as superoxidase dismutase, peroxidase, and catalase to reduce the toxic levels of these intermediates. 

Once simple sulfides (thioethers) enter the systemic circulation, they are rapidly oxidized to sulfoxides and, depending on the structure of the thioether, may be further oxidized to sulfones. Aliphatic thioethers yield mixtures of sulfoxide and sulfone urinary metabolites (Damani, 1987). Enzymes of the cytochrome P450 superfamily and flavin-containing monooxygenases catalyse the oxidation of thioethers to sulfoxides (Renwick, 1989). Oxidation of sulfoxides to the corresponding sulfones occurs both in tissues and in aerobic microorganisms and is an irreversible metabolic reaction in mammals (Damani, 1987). Sulfoxides can also be metabolized back to the thioether by thioredoxin and its reductase and by the gut microflora in the anaerobic environment of the lower bowel (Lee Renwick, 1995). 

This discussion will be limited to aerobic hydroxylation reactions. As already mentioned, it is a reaction which appears to be restricted to the metabolism of rather inert molecules. The reason for this is not apparent, but it may be because the reaction is energetically expensive for the cell. If, in the hydration type of hydroxylation reaction, a pyridine nucleotide functions as the hydrogen acceptor, the subsequent reoxidation of the DPNH or TPNH over the flavin-cytochrome hydrogen transport system could be coupled to the synthesis of 3 moles of ATP per mole of DPNH oxidized. In the aerobic type of hydroxylation reaction, utilizing TPNH as the electron donor, the oxidation of the TPNH is apparently not coupled to high-energy phosphate-bond synthesis and the cell therefore loses the equivalent of three ATP s. 

---