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Microsomal enzyme induction, egg production, and reproduction in three lines of Japanese quail fed polybrominated biphenyls.

The sensitivity of three genetic lines of Japanese quail to polybrominated biphenyls (PBBs) was evaluated using criteria of egg production, reproduction, and induction of the hepatic microsomal mixed-function oxidase (MFO) system. Two genetic lines of quail, developed to diverge in their plasma cholesterol response to exogenous adrenocorticotropin (ACTH) (a "Low" line and a "High" line), were compared to a random-bred line ("Random"). ACTH administration caused increases in plasma cholesterol in the Low line that were 15 and 39% below the Random-line values in males and females, respectively, while High-line values were 31% higher in males and 36% higher in females when compared to the respective Random-line values. Hepatic activities of aryl hydrocarbon hydroxylase (AHH) and hexobarbital hydroxylase (HxH) were not significantly influenced by ACTH administration or by genetic line in either sex. PBBs fed at 40 or 80 mg/kg diet for 5 wk resulted in significant increases in hepatic AHH and aminopyrine N-demethylase (APND) activities and cytochrome P-450 concentrations. The induction of AHH, APND, and cytochrome P-450 was significantly less in Low-line males in comparison to Random- and High-line males, while the induction of AHH was less in Low-line females when compared to females from the other two lines, based on covariance analysis. In terms of reproductive parameters, there was a greater adverse effect on egg production at 80 ppm PBBs in Low-line females when compared to the Random and High lines. These data indicate an example in which the biological toxicity of a compound and the induction of a 3-methylcholanthrene-type hepatic enzyme are not directly correlated.

Adrenocorticotropic Hormone↗

Enzyme induction by phenobarbitone and vitamin K1 disposition in man.

The plasma disposition of an intravenous pharmacological dose of vitamin K1 was determined in seven healthy volunteers before and after chronic administration of phenobarbitone (100 mg nocte). Phenobarbitone produced a significant increase in antipyrine clearance and 6 beta-hydroxycortisol excretion in all volunteers, indicating induction of hepatic microsomal mixed-function oxidase enzymes. However, phenobarbitone administration had no effect on the plasma disposition of vitamin K1. We conclude therefore, that vitamin K1 is not metabolized to any significant extent, by phenobarbitone-inducible mixed-function oxidase enzymes.

Antipyrine↗

Penicillinamidohydrolase in Escherichia coli. III. Catabolite repression, diauxie, effect of cAMP and nature of the enzyme induction.

Synthesis of penicillinamidohydrolase (penicillin acylase, EC 3.5.1.11) in Escherichia coli is subjected to the absolute catabolite repression by glucose and partial repression by acetate. Both types of catabolite repression of synthesis of the enzyme in Escherichia coli are substantially influenced by cyclic 3',5'-adenosinemonophosphate (cAMP). Growth diauxie in a mixed medium containing glucose and phenylacetic acid serving as carbon and energy sources is overcome by cAMP. cAMP does not influence the basal rate of the enzyme synthesis (without the inducer). Derepression of synthesis of penicillinamidohydrolase by cAMP in a medium with glucose and inducer (phenylacetic acid) is associated with utilization of the inducer, due probably to derepression of other enzymes responsible for degradation of phenylacetic acid. Lactate can serve as a "catabolically neutral" source of carbon suitable for the maximum production of penicillinamidohydrolase. The gratuitous induction of the enzyme synthesis in a medium with lactate as the carbon and energy source and with phenylacetic acid is not influenced by cAMP; however, cAMP overcomes completely the absolute catabolite repression of the enzyme synthesis by glucose.

Acetates↗

Enzyme induction in cultured human hair follicle cells.

The enzyme aryl hydrocarbon hydroxylase is present in murine and human cultures of keratinocytes. While the activity of aryl hydrocarbon hydroxylase in murine cultures was found to be inducible after exposure to benz(a)anthracene, human keratinocytes originating from the hair follicle did not respond to this treatment. Hence, cultured human keratinocytes are not suitable for studying the molecular events that mediate the process of aryl hydrocarbon hydroxylase induction.

Animals↗

L-Tryptophan action on hepatic RNA synthesis and enzyme induction.

L-Tryptophan increases the activity of hepatic amino acid metabolizing enzymes, affects gluconeogenesis and displays a modulatory effect on several enzymes connected with RNA synthesis. The underlying mechanism differ in individual cases and result in both an increase of enzyme synthesis de novo and a decrease of enzyme degradation. Tryptophan displays a unique effect causing aggregation of hepatic polyribosomes connected with enhanced protein synthesis and preceded by a higher transport of poly (A) messenger RNA from the nucleus to the cytoplasm. The variety of rather specific effects mediated by tryptophan brings to mind hormonal action and the existence of specific tryptophan receptors is predicted.

Amino Acids↗

Inhibition of hepatic enzyme induction as a sensitive assay for endotoxin.

Bacterial endotoxins in mice reduced the induction by cortisone of two hepatic enzymes, tryptophan oxygenase, and phosphoenolpyruvate carboxykinase, they prevented the glyconeogenesis in liver induced by the same hormone, and they induced in intact animals the liver enzyme tyrosine-alpha-ketoglutarate transaminase, all in proportion to their ld(50). When cortisone was given in the least amount (100 mug), it resulted in near maximal induction of tryptophan oxygenase; a smaller amount of endotoxin reduced significantly the level of enzyme than that required when 5 mg of hormone was injected. The smallest amount of endotoxin that prevented tryptophan oxygenase induction was given intravenously to adrenalectomized mice in which 25 mug of cortisone was administered. The amount (0.01 mug) is 1/40,000th of the ld(50). The other metabolic processes subject to alteration by endotoxin required at least 100 to 400 times as much. This property of endotoxin can serve as a sensitive bioassay, although the dose-response curve is steep.

Adrenalectomy↗

Induction of sister-chromatid exchanges by direct and indirect mutagens in human lymphocytes, co-cultured with intact rat liver cells. Effect of enzyme induction and preservation of the liver cells by freezing in liquid nitrogen.

An in vitro assay system using intact rat hepatocytes and human peripheral lymphocytes is described which has been developed with the aim of bringing test conditions closer to in vivo conditions, thereby broadening the available battery of simple in vitro assays. A culture vessel, which contains an inner chamber with a semipermeable bottom, has been designed to allow easy removal of the hepatocytes. Determination of sister-chromatid exchange rate was used as the experimental end point. For validation, a series of chemicals were used which have been tested previously in a large interlaboratory investigation of short-term test methods. Our study supplies complementary information to this investigation in as much as some chemicals could be correctly assigned as positive or negative, in contrast to what was found in the earlier tests. Furthermore, we show that the metabolic capacity of both normal and induced liver cells can be preserved in liquid nitrogen for long periods.

Animals↗