Induction of the Drug-Metabolizing Enzymes

Parke, Dennis V.

doi:10.1007/978-1-4615-8954-9_8

Cited by 39 publications

(19 citation statements)

References 199 publications

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“…Many Cyt P-450 monooxygenases involved in catabolic transformations in animals, microbes, and plants are induced by treatment with the corresponding oxygenase substrate (Parke, 1957;Benveniste et al, 1982;Sligar and Murray, 1986). Cyt P-450 monooxygenase systems in plants have also been induced by treatment with growth hormones, heavy metals, and other xenobiotics (Reichhart et al, 1980;Adele et al, 1981).…”

Section: Induction Of Camphor-6-exo-hydroxylasementioning

confidence: 99%

Induction and Characterization of a Cytochrome P-450-Dependent Camphor Hydroxylase in Tissue Cultures of Common Sage (Salvia officinalis)

Funk

Croteau

1993

Plant Physiol.

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(+)-Camphor, a major monoterpene of the essential oil of common sage (Salvia officinalis), is catabolized in senescent tissue, and the pathway for the breakdown of this bicyclic ketone has been previously elucidated in sage cell-suspension cultures. In the initial step of catabolism, camphor is oxidized to 6-exo-hydroxycamphor, and the corresponding NADPH-and O,-dependent hydroxylase activity was demonstrated in microsomal preparations of sage cells.Severa1 well-established inhibitors of cytochrome P-450-dependent reactions, including cytochrome c, clotrimazole, and C O , inhibited the hydroxylation of camphor, and CO-dependent inhibition was partially reversed by blue light. Upon treatment of sage suspension cultures with 30 mM MnCI2, camphor-6-hydroxylase activity was induced up to 7-fold. A polypeptide with estimated molecular mass of 58 kD from sage microsomal membranes exhibited antigenic cross-reactivity in western blot experiments with two heterologous polyclonal antibodies raised against cytochrome P-450 camphor-5-exo-hydroxylase from Pseudomonas putida and cytochrome P-450 limonene-6s-hydroxylase from spearmint (Mentha spicata). Dot blotting indicated that the concentration of this polypeptide increased with camphor hydroxylase activity in microsomes of Mn'+-induced sage cells. These results suggest that camphor-6-exo-hydroxylase from sage is a microsomal cytochrome P-450 monooxygenase that may share common properties and epitopes with bacterial and other plant monoterpene hydroxylases.The biosynthetic capacity of plant cell cultures to produce various monoterpenoid, sesquiterpenoid, and diterpenoid substances has been demonstrated; however, the accumulation of monoterpenes in cultured cell systems is only rarely observed (Banthorpe et al., 1986; Charlwood et al., 1989). Studies with undifferentiated suspension cultures of common sage (Salvia officinalis) showed that the enzymes directly responsible for the conversion of the ubiquitous isoprenoid precursor, geranyl pyrophosphate (Fig. 1, structure l)', to (+)-camphor (Z), a major monoterpene of the intact plant, were readily detected during the late logarithmic phase of growth. Yet, no significant accumulation of camphor (C0.3 ng/g fresh

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Section: Induction Of Camphor-6-exo-hydroxylasementioning

confidence: 99%

Induction and Characterization of a Cytochrome P-450-Dependent Camphor Hydroxylase in Tissue Cultures of Common Sage (Salvia officinalis)

Funk

Croteau

1993

Plant Physiol.

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“…Although the enzyme system responsible for glucuronide formation is inducible (Blaschke, Berk, Rodkey, Scharschmidt, Collison & Waggoner, 1974;Lecamwasam, 1975;Parke, 1975), animal studies indicate that the stimulation of hepatic microsomal enzymes by phenobarbitone is associated with changes in several other measures of liver function, each of which could theoretically result in enhancement of metabolic drug clearance. These include increased concentration in the hepatocyte of the Y organic anion-binding protein (Reyes, Levy, Gatmaitan & Arias, 1971), increased bile flow (Redinger & Small, 1973) and increased liver blood flow (Ohnaus, Thorgeirsson, Davies & Breckenridge, 1970;Branch, Shand, Wilkinson & Nies, 1974;Nies, Wilkinson, Rush, Strother & McDevitt, 1977).…”

Section: Pharmacokinetic Analysismentioning

confidence: 99%

“…Chronic administration of therapeutic agents such as barbiturates and phenytoin, or exposure to environmental contaminants such as DDT, lindane, certain food additives, may induce the activity of drug metabolizing enzymes in hepatic microsomes (Conney, 1967;Kuntzman, 1969;Parke, 1975). A large number of clinically important drug interactions have been attributed to this mechanism (Breckenridge, 1975;Hunter & Chasseaud, 1976).…”

Section: Introductionmentioning

confidence: 99%

Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs.

Perucca¹,

Richens²

1979

Brit J Clinical Pharma

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1 The serum concentration profile of paracetamol has been determined after administration of single 1000 mg intravenous and oral doses in six normal subjects and six epileptic patients on chronic antiepileptic drug therapy. The urinary excretion of free and conjugated paracetamol has also been determined. 2 Following intravenous administration, serum paracetamol concentration declined with first‐order kinetics. Both elimination rate and total body clearance were higher in the epileptic patients, although in neither case was the difference statistically significant. 3 The oral bioavailability (mean +/‐ s.e. mean) was significantly lower in the epileptic patients than in the normal subjects (0.77 +/‐ 0.03 and 0.89 +/‐ 0.02 respectively, P less than 0.01), whereas the urinary excretion total (free+conjugated) paracetamol was almost identical in the two groups. 4 It is suggested that the lower bioavailability of paracetamol in the epileptic patients results from enhancement of first‐pass metabolism, secondary to enzyme induction.

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“…That these enzyme activities were inducible suggested they would be of clinical importance in pharmacology and therapeutics [4][5][6][7]. A few laboratories also recognized that P450 enzymes participated in steroid and fatty acid hydroxylation in both adrenal cortex and liver [8,9].…”

Section: Introductionmentioning

confidence: 99%

Human cytochromes P450 in health and disease

Nebert

Wikvall

Miller

2013

Phil. Trans. R. Soc. B

425

305

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There are 18 mammalian cytochrome P450 (CYP) families, which encode 57 genes in the human genome. CYP2, CYP3 and CYP4 families contain far more genes than the other 15 families; these three families are also the ones that are dramatically larger in rodent genomes. Most (if not all) genes in the CYP1, CYP2, CYP3 and CYP4 families encode enzymes involved in eicosanoid metabolism and are inducible by various environmental stimuli (i.e. diet, chemical inducers, drugs, pheromones, etc.), whereas the other 14 gene families often have only a single member, and are rarely if ever inducible or redundant. Although the CYP2 and CYP3 families can be regarded as largely redundant and promiscuous, mutations or other defects in one or more genes of the remaining 16 gene families are primarily the ones responsible for P450-specific diseases-confirming these genes are not superfluous or promiscuous but rather are more directly involved in critical life functions. P450-mediated diseases comprise those caused by: aberrant steroidogenesis; defects in fatty acid, cholesterol and bile acid pathways; vitamin D dysregulation and retinoid (as well as putative eicosanoid) dysregulation during fertilization, implantation, embryogenesis, foetogenesis and neonatal development.

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Induction of the Drug-Metabolizing Enzymes

Cited by 39 publications

References 199 publications

Induction and Characterization of a Cytochrome P-450-Dependent Camphor Hydroxylase in Tissue Cultures of Common Sage (Salvia officinalis)

Induction and Characterization of a Cytochrome P-450-Dependent Camphor Hydroxylase in Tissue Cultures of Common Sage (Salvia officinalis)

Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs.

Human cytochromes P450 in health and disease

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