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Aniline Hydroxylase
About: Aniline Hydroxylase is a research topic. Over the lifetime, 467 publications have been published within this topic receiving 9542 citations.
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Journal Article•
TL;DR: Although liver microsomes from male rats metabolize most drugs more rapidly than do those from female rats, the magnitude of the sex difference varies markedly with the substrate and the effects of starvation of male rats range from impairment of sex-dependent enzymes which metabolize aminopyrine and hexobarbital to enhancement of thesex-independent enzyme that hydroxylates aniline.
Abstract: Although liver microsomes from male rats metabolize most drugs more rapidly than do those from female rats, the magnitude of the sex difference varies markedly with the substrate. There is more than a 3-fold sex difference with substrates like aminopyrine and hexobarbital, but virtually no sex difference in the hydroxylation of aniline and zoxazolamine. The effects of starvation of male rats range from impairment of sex-dependent enzymes which metabolize aminopyrine and hexobarbital to enhancement of the sex-independent enzyme that hydroxylates aniline. In contrast, starvation of female rats increases the specific activity of the aminopyrine- and hexobarbital-metabolizing enzymes as well as aniline hydroxylase. Since the sex-dependent enzymes are impaired in fasted male rats but enhanced in fasted female rats, starvation diminishes if it does not abolish the sex difference in the metabolism of drugs by rat liver microsomes. Starvation does not alter the metabolism of hexobarbital and enhances the metabolism of aminopyrine by liver microsomes from castrated rats, but impairs the metabolism of these compounds by liver microsomes from castrated rats receiving methyltestosterone.
543 citations
TL;DR: Cytochrome P-450 was purified from liver microsomes of phenobarbital-pretreated rabbits to a specific content of 16 to 17 nmoles per mg of protein with a yield of about 10 %.
Abstract: Cytochrome P-450 was purified from liver microsomes of phenobarbital-pretreated rabbits to a specific content of 16 to 17 nmoles per mg of protein with a yield of about 10 % The purified cytochrome yielded only a single protein band on sodium dodecylsulfate-urea-polyacrylamide gel electrophoresis, and an apparent molecular weight of about 45,000 was estimated for the protein The preparation was free of cytochrome b 5 , NADH-cytochrome b 5 reductase, and NADPH-cytochrome c reductase activities Aniline hydroxylase and ethylmorphine N-demethylase activities could be reconstituted upon mixing the purified cytochrome with an NADPH-cytochrome c reductase preparation (purified by a detergent method) and phosphatidyl choline
291 citations
TL;DR: Hepatic lipids, smooth endoplasmic reticulum, and the activities of drug-metabolizing enzymes were increased with the adequate diet but more so with the deficient one, which may explain the increased tolerance by alcoholics of drugs such as sedatives.
Abstract: Rats were fed ethanol for 2 weeks along with diets either adequate or deficient in protein and choline, the latter intake being similar to that of many alcoholics. Hepatic lipids, smooth endoplasmic reticulum, and the activities of drug-metabolizing enzymes (aniline hydroxylase and nitroreductase) were increased with the adequate diet but more so with the deficient one. These results may explain the increased tolerance by alcoholics of drugs such as sedatives.
240 citations
TL;DR: The data indicate that the profile of microsomal oxidase enzymes and their control undergo striking changes as hepatocytes adapt to cell culture.
Abstract: Primary monolayer culture of adult rat hepatocytes represents a novel and potentially useful technique to study many aspects of hepatic physiology for extended periods of time in vitro (J Cell Biol 59:722–734,1973). In examining the hepatic drug-metabolizing system in these cells, we have discovered that the conditions of cell culture exert rapid, selective, and reproducible changes in microsomal enzymes. In the 24- to 48-hr period immediately following preparation and culture of the isolated parenchymal cells, the level of the drug-binding microsomal hemoprotein, cytochrome P-450, measured in extracts of cell homogenates, declined to less than 20% of its in vivo level, whereas NADPH-cytochrome c reductase activity was only moderately reduced and glucose-6-phosphatase activity remained unchanged. The activity of aminopyrine-N-demethylase and aniline hydroxylase also fell, paralleling the level of cytochrome P-450. By contrast, p-nitroanisole O-demethylase activity was unchanged in the cultured hepatocytes despite evidence (type I binding spectrum, NADPH requirement, inhibition by carbon monoxide or by SKF 525A) that p-nitroanisole O-demethylase is a cytochrome P-450-dependent enzyme. In culture, as in vivo, aromatic polycyclic hydrocarbons stimulated p-nitroanisole O-demethylase and aryl hydrocarbon (benzo[α]pyrene) hydroxylase activities; however, this effect was unaccompanied by a detectable increase in total carbon monoxide-binding hemoprotein. The data indicate that the profile of microsomal oxidase enzymes and their control undergo striking changes as hepatocytes adapt to cell culture.
221 citations
Journal Article•
TL;DR: Results are consistent with activation of CCl 4 by cy tochrome P -450 to a reactive short-lived radical which initiates peroxidation in the immediate vicinity of the cytochrome and thereby inhibits enzyme activity either by destruction of essential lipids or by direct attack on the enzyme by reactive intermediates of the peroxidative process.
Abstract: Carbon tetrachloride initiated lipid peroxidation in isolated rat liver microsomes in the absence of free metal ions. In contrast to the nonenzymatic process stimulated by ferrous iron, CCl 4 -induced peroxidation showed an absolute requirement for NADPH and appeared dependent on the integrity of cytochrome P -450 as reflected by measurement of aminopyrine demethylase and aniline hydroxylase activities. The peroxidation subsided after only 10% of the total peroxidizable polyunsaturated fatty acids had reacted, at which point the cytochrome P -450 activities were 85-95% inhibited, whereas NADPH-cytochrome P -450 reductase activity was not significantly affected. Ferrous iron, in contrast, caused peroxidation of 100% of the available polyunsaturated fatty acids and produced decreases in cytochrome P -450 activities as well as a loss of susceptibility to CCl 4 -induced peroxidation that approximately paralleled the extent of peroxidation. Thus, CCl 4 -induced peroxidation appeared to be 10 times more potent in inhibiting cytochrome P -450 activities than the peroxidation caused by iron. Boiled liver microsomes or liposomes prepared from extracted liver lipid underwent extensive peroxidation in the presence of untreated microsomes when ferrous iron was the initiating species. In contrast, the CCl 4 -induced peroxidative response was not affected by the addition of these exogenous forms of lipid substrate and thus the initiating species appeared to be confined to the active microsomes. No detectable peroxidation was induced by CCl 4 in microsomes from brain, kidney, or lung, and microsomal aminopyrine demethylase and aniline hydroxylase activities were more than 10-fold lower in these tissues compared to liver. These results are consistent with activation of CCl 4 by cytochrome P -450 to a reactive short-lived radical which initiates peroxidation in the immediate vicinity of the cytochrome and thereby inhibits enzyme activity either by destruction of essential lipids or by direct attack on the enzyme by reactive intermediates of the peroxidative process. Loss of cytochrome P -450 activity then results in cessation of the CCl 4 -induced peroxidative response prior to more extensive reaction of membrane polyunsaturated lipids.
172 citations