Disease relevance of Enzyme Induction

• Coronary heart disease, cancer, lipoproteins, and the effects of clofibrate: is enzyme induction a common link and are lipoproteins red herrings [1]?
• Leiomyoblastoma associated with intractable hypercalcemia and elevated 1,25-dihydroxycholecalciferol levels. Treatment by hepatic enzyme induction [2].
• The increased faecal mucin sulphatase activity in ulcerative colitis could be the result of greater intraluminal substrate (mucin) availability leading to bacterial enzyme induction, but would probably result in more rapid degradation of secreted mucin and represents a potential target for treatment [3].
• RESULTS: The end-stage renal disease group had 28% lower baseline erythromycin breath test values than controls (P <.05); however, enzyme induction capacity after rifampin administration was similar between groups (P =.70) [4].
• We consider it probable that pre-existing liver disease affects the response to ethanol, so that greater amounts of GGT are released from hepatic tissue; alternatively, drinkers may have a higher GGT activity in this tissue as a result of enzyme induction by ethanol [5].

Psychiatry related information on Enzyme Induction

• The present experiments also indicate that the primary cause for increased serum gamma-glutamyltransferase activities associated with prolonged alcohol consumption is hepatic enzyme induction rather than liver cell injury [6].
• Nitrazepam does not seem to cause enzyme induction with lowered plasma levels and may therefore be of special value in the treatment of chronic insomnia [7].

High impact information on Enzyme Induction

• Enzyme induction is transiently sensitive to inhibition by actinomycin D, suggesting that increased concentrations of cAMP mediate the inducing effects of the hormones by enhancing the transcription of PA-mRNA sequences [8].
• Microsomal enzyme induction by methadone and its implications on tolerance to methodone lethality [9].
• The striking parallelism between protein kinase activity that is dependent on cytosol cyclic AMP and cellular responses to dibutyryl cyclic AMP in wild-type cells and three classes of clones resistant to cyclic AMP indicates that protein kinase mediates cyclic AMP regulation of growth and enzyme induction in S49 cells [10].
• Enzyme induction reflects increased transcription of the cognate CYP1A1 gene [11].
• Thus, increasing hepatic cholesterol does not directly inhibit cholesterol 7alpha-hydroxylase and initially favors enzyme induction, whereas increased bile acid pool is the most powerful inhibitor of cholesterol 7alpha-hydroxylase [12].

Chemical compound and disease context of Enzyme Induction

• The increase in tyrosine aminotransferase activity which occurs in rat hepatoma tissue culture (HTC) cells in response to cyclic AMP analogs has been shown to be an enzyme induction, similar to the larger response observed in certain other hepatoma cells and in liver [13].
• Hepatic enzyme induction by bezafibrate in rats results in hepatomegaly, but there has been no case of significant hepatotoxicity in man.(ABSTRACT TRUNCATED AT 400 WORDS)[14]
• Neither cefixime nor cefuroxime was a strong inducer of class I beta-lactamases, although enzyme induction did appear to play a role in cefuroxime resistance in a strain of Serratia marcescens [15].
• Guinea-pig model of halothane-associated hepatotoxicity in the absence of enzyme induction and hypoxia [16].
• Enzyme induction by L-buthionine (S,R)-sulfoximine in cultured mouse hepatoma cells [17].

Biological context of Enzyme Induction

• This alkylation dependent enzyme induction required protein synthesis for it did not occur in the presence of cycloheximide [18].
• Three DENSPM analogues that differentially induced SSAT activity but similarly depleted polyamine pools revealed a close correlation between enzyme induction and cytochrome c release, caspase activation, and apoptosis [19].
• Inhibition by sodium butyrate of enzyme induction by glucocorticoids and dibutyryl cyclic AMP. A role for the rapid form of histone acetylation [20].
• It has been assumed that this sensitivity in chronic alcoholics is due to microsomal enzyme induction with enhanced metabolic activation of acetaminophen [21].
• Enzyme induction in the elderly: effect of rifampin on the pharmacokinetics and pharmacodynamics of propafenone [22].

Anatomical context of Enzyme Induction

• Both pregnancy and estradiol treatment increased the amount of mRNAs for NOS isozymes eNOS and nNOS in skeletal muscle, suggesting that the increases in NOS activity result from enzyme induction [23].
• P-450 enzyme induction by 5-ethyl-5-phenylhydantoin and 5,5-diethylhydantoin, analogues of barbiturate tumor promoters phenobarbital and barbital, and promotion of liver and thyroid carcinogenesis initiated by N-nitrosodiethylamine in rats [24].
• However, since chronic ethanol consumption had no apparent effect on the incidence of nasal cavity tumors in rats treated by s.c. injection of NNN, factors other than enzyme induction are important in determining the effects of ethanol on NNN carcinogenicity [25].
• These findings provide further evidence that metal ions can regulate heme oxygenase synthesis directly in isolated liver cells and that the metal-metal interactions which lead to blockade of the enzyme induction do not involve extrahepatic tissues [26].
• The intracellular mechanisms involved in the regulation of creatine phosphokinase expression in the BC3H1 muscle-like cell line have been examined under conditions of enzyme induction and repression [27].

Associations of Enzyme Induction with chemical compounds

• Cyclic AMP-dependent protein kinase: pivotal role in regulation of enzyme induction and growth [10].
• DMSO and butyrate may affect the heme biosynthetic pathway by multiple mechanisms or, alternatively, they may affect the multistep pathway at various points, producing partial blocks or incomplete enzyme induction [28].
• Management of paracetamol poisoning complicated by enzyme induction due to alcohol or drugs [29].
• Clofibrate may act as an enzyme inducer and the hypothesis is that enzyme induction is responsible for this pattern [1].
• The association between serum G.G.T. and triglyceride, and their increase after treatment with oral contraceptives, may reflect hepatic microsomal enzyme induction of both the rate-limiting enzymes of triglyceride synthesis, and G.G.T [30].

Gene context of Enzyme Induction

• These results indicate that in uninduced mice, the normal Ah receptor facilitates formation of IQ/DNA adducts in liver and alters the profile of adducts in lung, via an unknown mechanism, whereas the Ah receptor-dependent enzyme induction reduces adducts in liver, probably due to increased detoxification, but increases them in lung [31].
• METHODS: We measured hepatic CYP3A activity at baseline and after rifampin (INN, rifampicin) enzyme induction in 12 patients with end-stage renal disease and 12 healthy, age-matched controls [4].
• We compared the performance of several modifications of the caffeine test for measurement of CYP1A2 activity in subjects with exceptionally high, low, or absent enzyme induction [32].
• CONCLUSIONS: Alterations in the activity of CYP3A4, CYP2C9 and FMO3 through genetic polymorphisms, enzyme induction or inhibition bear the potential to cause clinically significant changes in perazine clearance [33].
• However, associated with IL-1beta, TNF-alpha greatly potentiated this enzyme induction [34].

Analytical, diagnostic and therapeutic context of Enzyme Induction

• Measurement of angiotensin converting enzyme induction and inhibition using quantitative in vitro autoradiography: tissue selective induction after chronic lisinopril treatment [35].
• The stimulatory effects of testosterone and hypophysectomy on the enzyme induction were additive [36].
• Further, we have found that after refeeding a fat-free diet to fasted rats, increases in transcriptional rate, mRNA concentration and enzyme induction of hepatic malic enzyme and glucose-6-phosphate dehydrogenase were always lower in 18-month-old rats than in 1.5-month-old rats [37].
• 6. At doses typically used to achieve hepatic microsomal enzyme induction in man, phenobarbitone treatment caused no significant change or trend towards a change in serum AGP concentrations as measured using the radial immunodiffusion method in nonsmokers (67.4 +/- 19.9 mg dl-1 vs 68.0 +/- 40.7 mg dl-1) or smokers (64.5 +/- 15.7 vs 67.9 +/- 14.9) [38].
• When m-xylene was administered intraperitoneally, the effect of enzyme induction was shown only at the large dose, a finding which suggests that intraperitoneal administration is more similar to inhalation exposure than oral administration [39].

References