Cytochrome reductase activity, effect

The formation of nitric oxide in microsomes results in the inhibition of microsomal reductase activity. It has been found that the inhibitory effect of nitric oxide mainly depend on the interaction with cytochrome P-450. NO reversibly reacts with P-450 isoforms to form the P-450-NO complex, but at the same time it irreversibly inactivates the cytochrome P-450 via the modification of its thiol residues [64]. Incubation of microsomes with nitric oxide causes the inhibition of 20-HETE formation from arachidonic acid [65], the generation of reactive oxygen species [66], and the release of catalytically active iron from ferritin [67],... 

In a recent investigation to develop novel cytochrome P450 biocatalysts, DNA shuffling was used to produce chimeric cytochrome P450s mutants with enhanced biocatalytic activities, which were then co-expressed with NADPH-cytochrome reductase in E. coli to form an efficient system, in this case demonstrated to be effective for indole oxidation [69]. 

Nitromethane was administered intraperitoneally (200 mg/kg bw) to male Wistar rats (three months of age) as a 10% solution in olive oil. The effects of nitromethane in the liver were detected only 48 h after administration and included a decrease in NADPH-cytochrome c reductase activity with proliferation of the smooth endoplasmic reticulum. Nitromethane also caused an increase in brain acid proteinase (4 h after injection) and acetylcholine esterase activities (4, 24 and 48 h after injection) (Zitting etal, 1982). 

Marked decreases in NADPH cytochrome P-450 reductase activity were consistently seen when BHT was included in the diet of male rats (24) but no significant effects were noted in female rats (27). 

A very important conclusion was reached based on the effect of p-mer-curibenzoate on the NADPH oxidase and the NADPH-cjrtochrome c reductase activities of microsomes, namely, that the natural acceptor might be a component reactive with oxygen and involved in hydroxyla-tions or demethylations (11). It was found that in the absence of cytochrome c, the oxidase activity was largely inhibited by p-mercuri-benzoate. In the presence of cytochrome c, NADPH oxidation exceeded cytochrome c reduction in the absence of p-mercuribenzoate and the two rates equaled each other in the presence of p-mercuribenzoate. Thus, a mercurial sensitive oxidase distinct from the reductase was indicated, and this component was hypothesized to be connected with hydroxylation and/or demethyktion (11). 

Ferricyanide appears to accept electrons from both the flavin and the heme (299-302), and it is believed that heme is required for cytochrome c reduction. Forestier and Baudras (302) have reported that, by treatment with guanidinium chloride, preparations of cytochrome 62 could be rendered partially deficient in flavin and heme. Thus, enzyme preparations were obtained which contained 65-75% flavin and variable amounts of heme from about 12 to 100%. The low heme preparations showed considerably greater loss of cytochrome c reductase than ferricyanide reductase activity. When preparations with increasing content of heme relative to flavin were tested, both the ferricyanide and the cytochrome c reductase activities increased as a linear function of heme to flavin ratio (up to heme flavin =1), but the increase in the heme content had a much greater effect on the cytochrome c reductase activity of the enzyme. The apoenzyme of cytochrome 62 has been prepared. However, reconstitution with FMN, heme, and FMN plus heme in all cases resulted in extremely... 

Table 10. Effect of erythrocuprein on cytochrome-c reductase activity of flavoproteins. The cytochrome-c reductase activity was measured in air-equilibrated solutions containing 0.1 M pyrophosphate, pH 8.5, in the presence of 3.33 X 70-5 M cytochrome c and 10 fig bovine catalase. The concentration of erythrocuprein in this assay mixture was 0.62 fiM. The temperature was 25° (150)...

Baldwin RL, Wells MR (1978) Effect of DDT on NADH-cytochrome K, reductase activity in the freshwater planarian, Phagocata velata. Bull Environ Contam Toxicol 19 428-430... 

Because other liposoluble vitamins (K and E) have often been implicated in the electron transport chain, the effects of vitamin A on mitochondria and mitochondrial enzymes have also been investigated. Although the mitochondrial respiration rate may be decreased in vitamin A-deficient animals, there is no change in the activity of succinoxidase or the enzymes of the Krebs cycle. Some investigators claim that cytochrome c reductase activity is decreased in tissues of vitamin A-deficient animals. A decrease in trans-hydrogenase activity of liver mitochondria and an increase in NADPH cytochrome c reductase has also been described in vitamin A deficiency. Ubiquinone is consistently in excess in deficient rats but not in chickens. 

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