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)

Oxidative demethylation of dimethylnitosamine was studied with both reconstituted and unresolved liver microsomal cytochrome P-450 enzyme systems from rats and hamsters. Proteinase treatment of liver microsomal preparations yielded cytochrome P-450 particulate fractions. Both cytochrome P-450 and NADPH- cytochrome c reductase fractions were required for optimum demethylation activity. Particulate cytochrome P-450 fractions were more effecient than either Triton X-100- or cholatesolubilized preparations of these particles in demethylation activity with rat and hamster liver preparations appear to be due to differences in specificity in their cytochrome P-450 fractions.
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PMID:Dimethylnitrosamine demethylation by reconstituted liver microsomal cytochrome P-450 enzyme system. 81 3

Administration of a single acute dose (20 mg/kg body weight) of methadone hydrochloride to both male and female mice increased the specific activity of NADPH-cytochrome c reductase and did not change much the content of cytochrome P-450 of their liver microsomes. Administration of multiple acute doses of methadone in male mice increased the specific activity of cytochrome c reductase and the content of cytochrome P-450 of their liver microsomes. Chronic administration of progressively increasing doses of methadone (up to 40 mg/kg body weight) to male mice increased the specific activity of c reductase. Similar chronic administration of methadone up to 28 mg/kg body weight also increased the microsomal content of P-450, but with higher doses of methadone, the content of P-450 declined and finally dropped slightly below control levels. The levels of c reductase activity and P-450 content returned to normal about two weeks after discontinuation of methadone administration.
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PMID:Influence of acute and chronic administration of methadone hydrochloride on NADPH-cytochrome c reductase and cytochrome P-450 of mouse liver microsomes. 82 9

The effect of mestranol on drug-metabolizing enzymes was studied in female rats receiving either deficient or thiamin-supplemented diets. Rats on the deficient diet showed increased hepatic microsomal activity of aniline hydroxylase, ethylmorphine demethylase, NADPH cytochrome c reductase, and cytochrome P-450. There were also increased concentrations of microsomal docosahexaenoic acid and arachidinic acid. Rats on the thiamin-supplemented diet showed decreased binding of aniline to microsomes, which was due to decreased levels of cytochrome P-450. However, high levels of thiamin decreased the binding of ethylmorphine to P-450. Mestranol increased ethylmorphine and aniline metabolism to a greater degree in animals receiving the thiamin-supplemented diet than those receiving the deficient diet or laboratory feed. However, levels of cytochrome P-450, cytochrome c reductase, or microsomal proteins were not increased, and the binding of aniline to cytochrome P-450 was not affected. Generally, treatment with mestranol decreased the binding of ethylmorphine. It appears that mestranol alters the Type I binding site on cytochrome P-450, but has no effect on the Type II binding site.
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PMID:Influence of the oral contraceptive, menstranol, on drug-metabolizing enzymes of female rats in thiamin-supplemented and deficiency states. 82 34

Male rats fed diet containing 3% corn oil for 3 weeks metabolized hexobarbital, aniline and heptachlor significantly faster than those fed fat-free diet. Half-maximal changes in aniline hydroxylation occurred in rats fed corn oil at approximately 0.1% of calories, whereas half-maximal changes in hexobarbital oxidase and heptachlor epoxidase occurred in rats fed corn oil at 1 to 1.5% of calories. Kinetic measurements of the drug-metabolizing enzyme system in washed microsomes revealed that maximal rate of aniline and ethylmorphine metabolism in male rats occurred with 3% corn oil diet, whereas maximal rate for hexobarbital occurred with 10% corn oil diet. In female rats maximal aniline hydroxylation occurred in rats receiving 10% corn oil diet. No alterations in Km for these reactions were observed in male or female rats fed 3% corn oil but were increased in rats fed 10% corn oil for those substrates whose maximal rate of metabolism was also increased (i.e., hexobarbital in males and aniline in females). Thus qualitative changes in microsomal drug-metabolizing enzymes may occur in rats ingesting diets containing 10% corn oil. Associated with the increased drug metabolism in corn oil-fed rats were increases in concentration of cytochrome P-450 in male and female rats, decreased sleeping time in male rats, and decreased glucose 6-phosphate dehydrogenase activity of male and female rats. No change in NADPH cytochrome c reductase activity was observed. Spectral binding measurements revealed increases in substrate binding associated with increased metabolism, most of which could be ascribed to the increases in cytochrome P-450. The spectral dissociation constant for these interactions between drug and oxidized cytochrome P-450 was unaltered with the exception that it was decreased in female rats fed 10% corn oil diet. Evidence of qualitative changes in the enzymes of endoplasmic reticulum was limited to those associated with an altered fatty acid composition of phospholipid and changes in the ethylisocyanide difference spectrum of reduced microsomes.
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PMID:Effect of dietary lipid on drug-metabolizing enzymes. 82 58

The effect of ethinyl estradiol, a steroid commonly used in birth control pills and possibly associated with impaired drug metabolism in humans, on the activity of and turnover of components of the hepatic microsomal mixed-function oxidase system was studied in male rats. After 5 days of ethinyl estradiol, 5 mg/kg/day, there was a significant decrease in the activity of ethylmorphine-N-demethylase and in cytochrome P-450, cytochrome b2, and NADPH cytochrome c reductase. Cytochrome P-450 apoproteins were identified within an SDS-polyacrylamide gel system, and the rate of turnover of cytochrome P-450 apoproteins was studied by double-isotope labeling techniques. After 5 days of ethinyl estradiol administration, the rate of degradation of cytochrome P-450 apoprotein was reduced (half-life of 50 hr compared to 24 hr in control), and their relative rate of synthesis was likewise reduced, indicating that a new steady state of protein turnover associated with reduced synthesis rate had been reached. This was confirmed by studies of the effect of ethinyl estradiol on the level of microsomal cytochrome P-450 over a 10-day period.
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PMID:Effects of ethinyl estradiol on hepatic microsomal proteins and the turnover of cytochrome P-450. 92 82

Dietary protein deficiency is known to modify the response to the pharmacotoxicological activities of drugs and foreign compounds, due in part to altered rates of metabolism. Prediction of whether in vivo susceptibilities to foreign compounds are increased or decreased in protein deficient animals has been said to be related to the relative toxicites of the metabolic products. We have shown that weanling rats fed semipurified casein diets for 15 days show a 75% depression of hepatic microsomal mixed function oxidase activities. About one-fourth of this decrease is due to a retardation of the normal rate of liver cell proliferation and less microsomal protein; the remaining three-fourths is due to a reduction of the specific enzyme activity. This latter decrease is closely correlated with similar decreases in cytochrome P-450 and cytochrome c reductase activities and cytochrome P-450 contents. Although protein deficiency affects the relative contents of phosphatidylcholine and cytochrome P-450, this does not result in modifications of the Km for metabolism, as is seen with phenobarbital administration in the various dietary groups. The depression of mixed function oxidase enzyme activities caused by feeding the protein deficient diet for 15 days can be restored to normal by feeding the 20% casein diets for an additional 30 days in the case of aniline hydroxylase but only partially in the case of ethylmorphine N-demethylase. The complexities of determining the role of metabolism as a modulator of protein deficiency effects on foreign compound toxicity are discussed.
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PMID:The effect of quantity and quality of dietary protein on drug metabolism. 97 91

The effect of inducing the rat liver nuclear mixed-function oxidase system by phenobarbital or 3-methylcholanthrene on NADPH- and NADH-dependent production of reactive oxygen intermediates was evaluated. The inducing agents produced a 2-fold increase in cytochrome P-450, a 50 to 70% increase in NADPH-cytochrome c reductase activity, and a 20 to 30% increase in NADH-cytochrome c reductase activity. Associated with these increases was a corresponding increase in NADPH- and NADH-dependent production of hydroxyl radical (.OH)-like species and of H2O2. Rates of .OH production were inhibited by catalase and partially sensitive to superoxide dismutase. The increase in nuclear production of .OH-like species after drug treatment appears to be due a corresponding increase in H2O2 generation. In contrast to H2O2 and .OH generation, production of thiobarbituric acid-reactive material by nuclei was not increased by the phenobarbital or 3-methylcholanthrene treatment. Redox cycling agents such as menadione and paraquat increased oxygen radical generation to similar extents in the control and the induced nuclei. These results indicate that induction of the nuclear mixed-function oxidase system by phenobarbital or 3-methylcholanthrene can result in a subsequent increase in production of reactive oxygen intermediates in the presence of either NADPH or NADH.
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PMID:Effect of phenobarbital and 3-methylcholanthrene treatment on NADPH- and NADH-dependent production of reactive oxygen intermediates by rat liver nuclei. 131 3

The intrauterine position of rat fetuses between siblings of the same or opposite sex has been reported to alter sexually dimorphic behavioral and reproductive traits in the adult. The intrauterine fetal position of adult rats is identified by a three letter code as mMm (a male, M, located between two male siblings, m-m) and fFf (a female, F, positioned between two females, f-f). This study sought to determine whether intrauterine location affected the hepatic polysubstrate monooxygenase and glutathione S-transferase activity, plasma sex steroid levels and organ weights in adult Long-Evans rats. The hepatic microsomal cytochrome P-450 content was higher in females located in utero between two male littermates (mFm) than in females positioned between two females (fFf). NADPH cytochrome c reductase activity was higher in mMm males (positioned in utero between two males) than in fMf males (males contiguous to two female littermates) and female rats. Hepatic microsomal testosterone 2 alpha- and 6 beta-hydroxylase activity was undetectable in fFf female but both activities were measurable in mFm female rats. Testosterone 7 alpha-hydroxylase and 5 alpha-reductase activity was higher in females than in males, and higher in fFf than in mFm females. Glutathione S-transferase activity was not altered by fetal contiguity in male and female rats. Adult mMm males had a higher plasma testosterone level and relative gonadal weight, and lower plasma estradiol concentration than fMf males. The plasma progesterone concentration of fFf female was lower than that of mFm female rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of intrauterine position on the hepatic microsomal polysubstrate monooxygenase and cytosolic glutathione S-transferase activity, plasma sex steroids and relative organ weights in adult male and female Long-Evans rats. 140 93

The major b-type cytochrome in microsomal membrane preparations from developing endosperm of castor bean (Ricinus communis) was cytochrome b5. Cytochrome P-450 was also present. The microsomal membranes had delta 12-hydroxylase activity and catalysed the NAD(P)H-dependent hydroxylation of oleate to yield ricinoleic acid. CO had no effect on the hydroxylase activity. Rabbit polyclonal antibodies were raised against the hydrophilic cytochrome b5 fragment purified from cauliflower (Brassica oleracea) floret microsomes. The anti-(cytochrome b5) IgG inhibited delta 12-hydroxylase, delta 12-desaturase and cytochrome c reductase activity in the microsomes. The results indicate that electrons from NAD(P)H were transferred to the site of hydroxylation via cytochrome b5 and that cytochrome P-450 was not involved.
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PMID:Evidence for cytochrome b5 as an electron donor in ricinoleic acid biosynthesis in microsomal preparations from developing castor bean (Ricinus communis L.). 141 66

The effect of selenium administered acutely or chronically on the hepatic microsomal drug-metabolizing system has been investigated in mice. After 72 h following acute administration of selenium (7.5 mg/kg, i.p.), there was a significant inhibition of the activities of aminopyrine (AM) N-demethylase and ethylmorphine (EM) N-demethylase, and cytochrome P-450 levels but no change in the activities of aniline (AN) hydroxylase, 7-ethoxycoumarin (EC) O-deethylase, reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase and reduced nicotinamide adenine dinucleotide (NADH)-ferricyanide reductase, and cytochrome b5 content. Chronic administration of selenium in the drinking water (1 or 2 ppm selenium) for 12 weeks, resulted in no alteration in any of the parameters measured. However, significant decreases in activities of AM N-demethylase and AN hydroxylase, and cytochrome P-450 levels were detected in animals given higher doses of selenium (4 or 8 ppm selenium). Following the in vitro additions of selenium to hepatic microsomes obtained from untreated mice, selenium inhibited the AM N-demethylase, AN hydroxylase and 7-EC O-deethylase in a concentration-dependent manner, but no alteration in NADPH-cytochrome c reductase and cytochrome P-450 levels was observed. These results indicate that selenium is a specific from inhibitor of hepatic monooxygenase.
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PMID:Inhibition of hepatic mixed-function oxidase enzymes in mice by acute and chronic treatment with selenium. 147 37


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