Reductive reactions quinone oxidoreductase

Succinate quinone oxidoreductases (EC 1.3.5.1 Hagerhall, 1997 Lancaster, 2002a,b) are enzymes that couple the two-electron oxidation of succinate to fumarate (reaction 1) to the two-electron reduction of quinone to quinol (reaction 2). 

They can also catalyze the opposite reaction, the coupling of quinol oxidation to quinone to the reduction of fumarate to succinate (Lemma et al., 1991). The m-configuration isomer of fumarate, maleinate, is neither produced in the oxidation reaction nor consumed as a substrate in the reduction reaction, i.e, the reaction is stereospecific in both directions. Depending on the direction of the reaction catalyzed in vivo, the members of the superfamily of succinate quinone oxidoreductases... 

Studies on metabolic stability using hepatocyte suspensions are not feasible for automation/HTS, but these studies do provide rather complete profiles of hepatic biotransformation without the supplements of cofactors and cosubstrates. The use of S9 in metabolic stability studies can be evaluated in a manner similar to that used for the microsomal assays, but with the possible addition of a broader panel of cofactors or cosubstrates. These include NADPH for CYP/FMO-mediated reactions, NADH for xanthine oxidoreductase and quinone oxidoreductase 2, NADPH-dependent reductions by carbonyl reductases, and NADPH/NADH-dependent reductions catalyzed by aldo-keto reductases, uridine 5 -diphosphate... 

The reductive biotransformation of drugs has been one of the least studied reactions, and many of the enzymes that are involved have not been well characterized. Some of the enzymes that catalyze reductive reactions of drugs are the cytochrome P450s, molybdenum reductases, alcohol dehydrogenases, carbonyl reductases, NADPH cytochrome P450 reductase, NAD(P)H— quinone oxidoreductases, and enzymes of the intestinal microflora (Matsunaga et al., 2006 Rosemond and Walsh, 2004). 

There is another mechanism that protects the cells from toxic effects of qui-nones. It is the reaction catalyzed by the NAD(P)H quinone oxidoreductase (NQO) (EC 1.6.5.2) enzyme. In this two-electron reduction the diol is formed. It can pass through the cell membrane. Getting to the extracellular space it can be detected amperometrically. The amperometric current in certain conditions reflects the NQO enzyme activity. 

Fig. 4.6. The proposed arrangement of the RC and h/c, complex in the photosynthetic chain of Rps. sphaeroides. The scheme indicates the reduction of Q to QHj by a pair of RC complexes and the net oxidation of QH2 by two turnovers of the oxidoreductase, as a balance of the oxidation of two quinols and the reduction of one quinone at the site. The proposed sites of proteolytic reactions are also indicated (from Ref. 93).

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