Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of redox systems in microsomes of brown adipose tissue (BAT) in cold exposed rats was investigated and compared with liver. BAT microsomes showed high activity of lipid peroxidation measured both by the formation of malondialdehyde (MDA) and by oxygen uptake. NADH and NADPH dependent cytochrome c reductase activity were present in both BAT and liver microsomes. Aminopyrine demethylase and aniline hydroxylase activities, the characteristic detoxification enzymes in liver microsomes could not be detected in BAT microsomes. BAT minces showed very poor incorporation of [1-14C]acetate and [2-14C]mevalonate in unsaponifiable lipid fraction compared to liver. Biosynthesis of cholesterol and ubiquinone, but not fatty acids, and the activity of 3-hydroxy-3-methyl glutaryl CoA reductase appear to be very low in BAT. Examination of difference spectra showed the presence of only cytochrome b5 in BAT microsomes. In addition to the inability to detect the enzyme activities dependent on cytochrome P-450, a protein with the characteristic spectrum, molecular size in SDS-PAGE and interaction with antibodies in double diffusion test, also could not be detected in BAT microsomes. The high activity of lipid peroxidation in microsomes, being associated with large oxygen uptake and oxidation of NADPH, will also contribute to the energy dissipation as heat in BAT, considered important in thermogenesis.
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PMID:Microsomal redox systems in brown adipose tissue: high lipid peroxidation, low cholesterol biosynthesis and no detectable cytochrome P-450. 210 21

Treatment of intact and hypophysectomized female rats with pregnenolone-16 alpha-carbonitrile (PCN) resulted in a significant increase in hepatic aryl hydrocarbon hydroxylase (AHH) activity. However, the total cytochrome P-450 concentration, as measured by CO difference spectra, was increased to a greater extent in hypophysectomized rats than in intact rats. Total cytochrome P-450 was found to be 0.82 +/- 0.16 vs 2.43 +/- 0.31 nmoles/mg protein for control and PCN-treated hypophysectomized rats, respectively, and 0.68 +/- 0.23 vs 1.28 +/- 0.05 nmoles/mg protein for control and PCN-treated intact rats respectively. The concentration of metyrapone complex in microsomes from intact control and PCN-treated rats was found to be 0.4 +/- 0.11 vs 1.88 +/- 0.23 M respectively. Treatment of hypophysectomized rats with PCN resulted in an approximate 10-fold increase in the concentration of the metyrapone complex (0.42 +/- 0.15 M for control and 4.46 +/- 0.44 M for PCN-treated). Microsomal NADPH and NADPH cytochrome c reductase activities were also altered by PCN-treatment. Aminopyrine demethylase activity was stimulated approximately three-fold by PCN treatment in both intact and hypophysectomized rats. Benzphetamine demethylase activity was not significantly affected by PCN treatment. The results of these studies suggest that the absence of the pituitary gland can markedly influence PCN induction of cytochrome P-450 in the liver in female rats. PCN also differentially affects microsomal mixed-function oxidase activities associated with drug and xenobiotic metabolism.
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PMID:Effects of pregnenolone-16 alpha-carbonitrile on drug metabolizing enzymes in hypophysectomized female rats. 361 68

Renal microsomal aminopyrine demethylation activities of several species were measured by a sensitive radiometric method using [dimethylamino-14C-]aminopyrine as a substrate and 2,4-dinitrophenylhydrazine as a trapping agent for the formaldehyde formed. The activity was highest in hamsters (0.75 nmol min-1 mg-1 protein) and that in rabbits, rats, mice, and guinea-pigs was 19.7, 7.0, 4.5 and 3.7%, respectively, of the hamster values. These species differences did not correlate with species differences in cytochrome P-450 content or in NADPH cytochrome c reductase activity. Aminopyrine demethylation activities in sliced renal tissues of several species were also compared. This activity was also found highest in hamsters (0.54 nmol min-1 g-1 wet tissue) and the activities in rabbits, rats, and guinea-pigs were 9.2, 1.8 and 2.5%, respectively, of the hamster values.
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PMID:Renal aminopyrine demethylation in several species determined by a sensitive radiometric method. 615 Sep 77

Effects of neutral salts on the drug-metabolizing enzyme system were measured in hepatic microsomes of rats in vitro. Aminopyrine N-demethylation was markedly enhanced by Li2SO4, Na2SO4, and K2SO4. Salts such as LiCi, NaCl, and KCl caused an enhancement of the demethylation following by an inhibition at high concentrations. KBr, Kl, and KSCN always inhibited the demethylation. Aniline hydroxylation, on the contrary, was not stimulated by the sulfates, and all other salts inhibited the hydroxylation with increasing concentration. The effectiveness of the neutral salts on changing aminopyrine or aniline oxidation activity followed Hofmeister's lyotropic series of ions: SCN- greater than 1- Br- greater than Cl- greater than SO4-- as anions and Li+ greater than Na+, K+ as cations. KSCN, Kl and KBr caused both the conversion of cytochrome P-450 to cytochrome P-420 and the inhibition of NADPH cytochrome c reductase activity; however, all other salts used in these experiments showed no change of those components. Enhancement of aminopyrine N-demethylation by the sulfates was reversible. It was concluded that cytochrome P-450 associated with aminopyrine N-demethylation is different from that of aniline hydroxylation in the hydrophobic environment of microsomes, and sulfate or chloride causes an enhancement of only cytochrome P-450 activity associated with the demethylation.
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PMID:Effects of neutral salts on hepatic microsomal drug-metabolizing enzyme system in rats. 641 37

Administration of caffeine, ip 100 mg/kg/day for 1-5 days, to adult male rats resulted in a significant increase in hepatic cytochrome P-450 and b5 concentrations and in cytochrome c reductase, aminopyrine N-demethylase and acetanilide hydroxylase activities. No change was seen in relative liver weight but microsomal protein content was increased after treatment for 1 day and decreased after treatment for 3 or 5 days. In adult rats given 25, 100 or 150 mg caffeine/kg for 3 days, maximum stimulation of mixed-function oxidases was seen with the 100-mg/kg dose. Caffeine treatment (100 mg/kg for 3 days) increased relative liver weight in female guinea-pigs and decreased it in chicks and female mice, and decreased microsomal protein content in male mice, female guinea-pigs and young rats, and increased it in chicks. A significant increase in hepatic cytochrome P-450 content was seen in all species studied. Cytochrome b5 content was increased in chicks and young rats, while cytochrome c reductase activity was increased in male and female mice, young rats and chicks and decreased in female guinea-pigs. Aminopyrine N-demethylase activity was increased in young rats and female guinea-pigs, and acetanilide hydroxylase was increased in all test species except male mice. In vitro addition of 2.5 mM-caffeine to microsomal incubations from untreated rats, guinea-pigs, mice and chicks inhibited aminopyrine N-demethylase activity, although only to a significant extent in male mice; addition of caffeine to incubations containing microsomes from caffeine-treated animals produced significant inhibition of aminopyrine N-demethylase activity in microsomes from adult and young rats and female guinea-pigs. Aminopyrine N-demethylase inhibition did not increase with increasing concentration of added caffeine, although acetanilide hydroxylase activity was progressively inhibited in the microsomal incubates from both control and caffeine-treated animals.
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PMID:In vivo and in vitro effects of caffeine on hepatic mixed-function oxidases in rodents and chicks. 653 86