Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Enzyme Induction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources
PubMed1975

Influence of double infections on the induction of thymidine kinase by UV-irradiated herpes simplex virus types 1 and 2 and pseudorabies virus.

Simultaneous infection of primary rabbit kidney cells with HSV type 1 TK+ and a TK- strain results in a mutual influence of both viruses on the induction of thymidine kinase (TK). TK+ virus has an enhancing and TK- virus a depressing effect on TK induction by a superinfecting TK+ virus. The enzyme induction depends on the ratio of multiplicities of both viruses. The mutual influence on TK induction depends further on the time of addition of the superinfecting virus: the effect of the second virus can still be observed when given 6 hours after primary infection. Identical phenomena can be observed using combinations with HSV type 2 or Pseudorabies viruses. The ability of HSV to induce TK is progressively inactivated with increasing the time of UV-irradiation. The depressing effect of a TK- strain and the stimulating effect of a TK+ strain on superinfecting TK+ strains is UV-sensitive: after 6 minutes of UV-irradiation neither inhibition nor stimulation of TK induction by a superinfecting TK+ strain can be observed. Infection by long-term (20 minutes) UV-irradiated TK+ strains results in a depression of TK induction by a superinfecting TK+ virus. Long-term irradiation of the TK- virus does not show this effect. Cytosine-arabinoside has no effect on the mutual influence of TK induction by TK+ and TK-strains; the phenomenon of mutual depression therefore has to be considered an early process.

Cell-Free System↗
PubMed2001

Longterm stability of phase I and phase II enzymes of porcine liver cells in flat membrane bioreactors.

Recently, researchers have focused on the use of bioartificial liver devices to support patients with fulminant hepatic failure. Our team developed a cell-based flat membrane bioreactor (FMB). In this, porcine liver cells were maintained in 3D-coculture between two gel layers in a sandwich configuration for 3 weeks to study the influence of this bioreactor technique on the preservation of basic, not induced activities of phase I and phase II enzymes. First, the time and substrate dependencies of the following enzymes were measured: ethoxyresorufin-O-deethylase (EROD, CYP 1A1/1A2) and ethoxycoumarin-O-deethylase (ECOD, CYP 2B6) as phase I enzymes, and glutathione-S-transferase (GST), UDP-glucuronosyltransferase (UGT) and sulfotransferase (ST) as phase II enzymes. To find optimal test conditions Michaelis-Menten kinetics were calculated. Next, different potential inducers were tested to find out the most effective compounds. Based on these results, the basic, not induced levels of the different enzymes were determined in the flat membrane bioreactor. Furthermore, the response of these enzyme activities to the chosen inducers was investigated to examine whether the cells keep their ability for drug-drug interactions. Basic, not induced activities of both phase I enzymes and the phase II enzymes GST and UGT were maintained at nearly the initial levels during the complete period of study. In addition, it was possible to induce these enzymes twice or three times in a weekly interval. In contrast, the basic, not induced activity of ST increased during the first 10 days of culture. It stabilized then and was maintained steady. As in short-term investigations, no reaction of the ST-activity towards any inducer could be obtained. These results prove that porcine liver cells preserve their phase I and phase II activities and respond to inducing drugs over 3 weeks in culture. Therefore, the flat membrane bioreactor is not only suitable for investigating drug metabolism, drug-drug interactions, and enzyme induction but also for supporting liver functions.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1998

In vitro evaluation of guar gum as a carrier for colon-specific drug delivery.

A novel tablet formulation for oral administration using guar gum as the carrier and indomethacin as a model drug has been investigated for colon-specific drug delivery using in vitro methods. Drug release studies under conditions mimicking mouth to colon transit have shown that guar gum protects the drug from being released completely in the physiological environment of stomach and small intestine. Studies in pH 6.8 phosphate buffered saline (PBS) containing rat caecal contents have demonstrated the susceptibility of guar gum to the colonic bacterial enzyme action with consequent drug release. The pre-treatment of rats orally with 1 ml of 2% w/v aqueous dispersion of guar gum for 3 days induced enzymes specifically acting on guar gum thereby increasing drug release. A further increase in drug release was observed with rat caecal contents obtained after 7 days of pre-treatment. The presence of 4% w/v of caecal contents obtained after 3 days and 7 days of enzyme induction showed biphasic drug release curves. The results illustrate the usefulness of guar gum as a potential carrier for colon-specific drug delivery. The study also reveals that the use of 4% w/v of rat caecal contents in PBS, obtained after 7 days of enzyme induction provide the best conditions for in vitro evaluation of guar gum.

Administration, Oral↗
PubMed1998

1 - 1. The chemistry and pharmacology of indole-3-carbinol (indole-3-methanol) and 3-(methoxymethyl)indole. [Part I].

Indole-3-carbinol (I3C) (2) is produced endogenously from naturally occurring glucosinolates contained in a wide variety of plant food substances including members of the family Cruciferae, and particularly members of the genus Brassica, whenever they are crushed or cooked. The acid environment of the gut very facilely converts it into a range of polyaromatic indolic compounds, e.g. (3, 4,5), which appear to be responsible for many of the physiological effects observed following the ingestion of these foods. 3-(Methoxymethyl)indole (6) is formed with great ease whenever 2 contacts methylating agents, including methanol, and it is often found as a contaminant of 2. This contamination is often not recognized or easily removed because of the great similarities of the two in melting points and solubilities. However, their biological properties are essentially identical. These so-called chemopreventive compounds are important because of their enzyme induction and suppression, mutagenic, carcinogenic and, particularly, antimutagenic and anticarcinogenic properties. The natural occurrence, formation, preparation, identification, separation, quantification, chemical transformations and general toxicological properties of these substances are critically reviewed in detail in this paper of 146 references, the first of two parts. The enzyme induction and suppression, mutagenic, antimutagenic, mutagenic, anticarcinogenic and carcinogenic effects will be published later as Part II. At the present time it appears that these have considerable potential as natural prophylactic anticancer agents against certain common neoplasms, especially inasmuch modern diets are increasingly deficient in these vegetable-derived substances.

Anticarcinogenic Agents↗
PubMed1981

Differential retinoic acid inhibition of ornithine decarboxylase induction by 12-O-tetradecanoylphorbol-13-acetate and by germicidal ultraviolet light.

Several retinoids including retinoic acid effectively inhibit phorbol ester-mediated tumor promotion and ornithine decarboxylase (ODC) induction in mouse epidermis. To understand better the possible cellular site of action of retinoids, the inhibitory action of retinoic acid on the induction of ODC was compared for two distinctly different inducers, namely, 12-O-tetradecanoylphorbol-13-acetate (TPA) and germicidal ultraviolet light (UV), in primary mouse epidermal cell cultures. It was found that the induction of ODC by TPA is almost completely prevented by 0.1 to 1 microM retinoic acid while the induction by UV is only moderately inhibited. Maximum inhibition is achieved by treating cells continuously with retinoic acid from 4 hr after plating, although pretreatment or simultaneous treatment relative to either inducer is almost as effective. When added after the inducer, retinoic acid loses its effectiveness as an inhibitor more rapidly for TPA induction than for UV induction of ODC. The differential inhibition of enzyme induction cannot be accounted for by selective retinoid inhibition of DNA, RNA, or protein synthesis either alone or in concert with TPA or UV. Other agents known to modulate the induction of ODC by TPA (fluocinolone acetonide, tosyl-L-lysylchloromethane, and local anesthetics) do not act differentially on UV induction. These agents possibly act at transcription or translation, both of which are required for ODC induction by TPA or UV. The preferential inhibition by retinoic acid of ODC induction by TPA is interpreted to result from specific interference at a unique and early site of interaction of TPA with the cell.

Animals↗
PubMed1983

Drug interactions affecting analgesic toxicity.

Most reports of interactions involving analgesics deal with their effects on the actions of other drugs rather than vice versa. Aspirin and ethanol have synergistic effects on the development of gastritis, gastrointestinal bleeding, and chronic gastric ulcer. This must be the most common and most important interaction affecting analgesic toxicity. Combined overdosage of aspirin with central nervous system depressants may be particularly hazardous because suppression of the salicylate-induced respiratory stimulation further shifts the disordered acid-base balance towards acidosis. The toxicity of acetaminophen (paracetamol) depends primarily on the balance between the rate of formation of the hepatotoxic metabolite and the rate of glutathione synthesis in the liver. In animals, prolonged pretreatment with ethanol increases the metabolic activation and acute toxicity of acetaminophen, and there is some evidence that chronic alcoholics are more susceptible to hepatotoxicity following acute overdosage. It has been assumed that this sensitivity in chronic alcoholics is due to microsomal enzyme induction with enhanced metabolic activation of acetaminophen. However, the metabolic activation of acetaminophen, as judged by the urinary excretion of its cysteine and mercapturic acid conjugates, is not increased in heavy drinkers or in patients induced by long-term treatment with anticonvulsants or rifampicin. Microsomal enzyme induction is complex. There are important species differences and different agents may selectively induce different variants of the multiple forms of cytochrome P-450. The acute administration of ethanol greatly reduces the metabolic activation of acetaminophen in heavy drinkers with more than a 50 percent decrease in cysteine and mercapturic acid conjugate production. Thus ingestion of ethanol should reduce the risk of liver damage following acetaminophen overdosage. Cimetidine, which inhibits the oxidative metabolism of some drugs, reduces the hepatotoxicity and increases the dose of acetaminophen in mice required to kill 50 percent of the animals. However, contrary to expectations, cimetidine does not inhibit the oxidative metabolism of acetaminophen in man. Salicylamide competes with acetaminophen for sulphate conjugation but is unlikely to potentiate toxicity following overdosage since sulphate conjugation is rapidly saturated anyway. Animal studies suggest that the hepatotoxicity of acetaminophen after overdosage may be increased by other agents which deplete glutathione, but there is no information on this point in man.

Acetaminophen↗
PubMed1996

The nifedipine-rifampin interaction. Evidence for induction of gut wall metabolism.

The calcium channel blocker nifedipine is metabolized by cytochrome P450 3A4, which is present in liver and mucosa of the small bowel. Cytochrome P450 3A4 is inducible by the tuberculostatic rifampin in liver and the small bowel. The contribution of gut wall metabolism to total clearance of nifedipine before and during induction has not been determined in detail. We therefore investigated the nifedipine-rifampin interaction, with special emphasis on the contribution of gut wall metabolism to total metabolism of nifedipine before and during administration of rifampin. Pharmacokinetics of nifedipine were studied in six healthy volunteers on separate days by administration of 20 micrograms/kg body weight nifedipine iv and 20 mg nifedipine orally before and after 7 days of rifampin treatment (600 mg/day). Enzyme induction did not significantly alter pharmacokinetics of nifedipine after iv administration. In contrast, oral clearance of nifedipine increased from 1.5 +/- 0.2 liters/min to 20.9 +/- 8.3 liters/min (p < 0.01) and bioavailability decreased from 41.2 +/- 5.4% to 5.3 +/- 2.7% (p < 0.001). Although hepatic extraction of nifedipine was not significantly altered during induction (47.4 +/- 6.6% versus 67.4 +/- 20.2%; ns), the calculated extraction of nifedipine in gut wall mucosa increased from 21.8 +/- 13.3% to 75.8 +/- 28.2% (p < 0.05). We conclude that there is a relevant interaction between nifedipine and rifampin. The reduction of nifedipine bioavailability during enzyme induction is most likely due to rifampin-induced gut wall metabolism.

Adult↗
PubMed1999

The high-affinity binding of [3H]norharman ([3H]beta-carboline) to the ethanol-inducible cytochrome P450 2E1 in rat liver.

High-affinity binding sites of [3H]norharman (synonymous: [3H]beta-carboline) were characterized in microsomal membranes from rat liver utilizing various beta-carboline (BC) derivatives and substances binding to enzymes of the cytochrome P450 (CYP) superfamily (EC 1.14.14.1). Saturation experiments demonstrated that [3H]norharman binds with high-affinity (dissociation constant 20.86 nM; maximum binding 21.40 pmol/mg protein). Displacement experiments with the beta-carboline derivatives 6-methyl-BC and 6-hydroxy-BC revealed a better adaptation to the two-site model, indicating that [3H]norharman binds to at least two sites, with an affinity of the high-affinity site in the low nM range. Substances binding with relative preference to isozymes of the CYP superfamily displaced [3H]norharman with a lesser potency than unlabeled norharman. Imidazole, pyrazole, and 4-methylpyrazole, known as inducers of the ethanol-inducible CYP2E1, displaced [3H]norharman with relative high potency. Furthermore, binding experiments with microsomes from human lymphoblast-expressed rat CYP2E1 revealed a high-affinity binding site [inhibition constant (Ki) 13.21 nM] comparable to that of microsomal membranes for norharman. It was displaceable by ethanol (Ki 14.25 microM), indicating that norharman and ethanol bind to the same binding site on CYP2E1. In vivo experiments with rats which had ingested ethanol for two weeks revealed that norharman blood plasma levels were significantly elevated at the end of this period, supporting the notion of an interaction of norharman and ethanol metabolism. Since it has been demonstrated in the Ames test that norharman's comutagenic action is connected with microsomal membranes (containing CYP isozymes), the present findings suggest that the observed increase in the levels of norharman in alcoholics leads to further CYP enzyme induction and thereby contributes to the increased risk of carcinomas in these patients.

Animals↗
PubMed1987

Alpha-melanocyte-stimulating hormone regulation of tyrosinase in Cloudman S-91 mouse melanoma cell cultures.

alpha-MSH (melanocyte-stimulating hormone) causes an increase in tyrosinase activity (O-diphenol-O2 oxidoreductase; EC 1.14.18.1) in Cloudman S-91 mouse melanoma cell cultures following a lag period of approximately 9 h. Treatment of cells with 2 X 10(-7)M alpha-MSH for 6 days results in a 90-fold increase in the specific activity of the enzyme. The hormone-mediated increase in tyrosinase activity is dependent upon continued transcription since the enzyme induction is suppressed by either cordycepin (1 microgram/ml) or alpha-amanitin (10 micrograms/ml). Immunoprecipitation analysis of pulse-labeled tyrosinase from control and MSH-treated cultures (48-h exposure) has demonstrated that MSH stimulates tyrosinase synthesis by approximately 4-fold, a level of induction which does not correspond to the observed 14-fold increase in enzyme activity. When immunotitration curves were developed from cell extracts of control and MSH-treated cultures using immunoprecipitation and competitive enzyme-linked immunosorbent assay protocols, evidence for the presence of immunologically active but catalytically less active enzyme in untreated melanoma cell cultures was demonstrated. Degradation rates of tyrosinase were found to be similar in control cultures or in cells treated with MSH for up to 48 h. Taken together, these results suggest that in addition to stimulating tyrosinase synthesis, MSH may also promote an increase in the catalytic efficiency of the enzyme.

Animals↗
PubMed1997

Effects of pantoprazole on xenobiotic metabolizing enzymes in rat liver microsomes: a comparison with other proton pump inhibitors.

The effects of pantoprazole on xenobiotic metabolizing enzymes in rat liver microsomes were examined. Groups of female Sprague-Dawley rats were orally administered pantoprazole and other proton pump inhibitors, omeprazole and lansoprazole, at 5, 50, or 300 mg/kg/day for 7 days, followed by assays to detect changes in the levels of liver microsomal protein, cytochrome P450, cytochrome b5, NADPH cytochrome c reductase, and drug metabolizing enzyme activities. Increases in total cytochrome P450 contents were evident after a 7-day high-dose administration of all the proton pump inhibitors tested, and the increase by treatment with pantoprazole was less than that with lansoprazole. The three proton pump inhibitors increased the enzymatic activities and cytochrome P450 enzyme levels of CYP1A, CYP2B, and CYP3A. CYP1A was less induced with pantoprazole than with omeprazole or lansoprazole. In contrast, CYP2B was more strongly induced with pantoprazole than with other proton pump inhibitors. NADPH cytochrome c reductase was induced with omeprazole and pantoprazole. The present results suggest that enzyme induction differs among these proton pump inhibitors not only quantitatively but also qualitatively.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

m-xylene toxicokinetics in phenobarbital-treated rats: comparison among inhalation exposure, oral administration, and intraperitoneal administration.

Rats, pretreated with phenobarbital (PB) for 3 days (80 mg/kg/day), were challenged with m-xylene orally or intraperitoneally at a small (0.01 ml/kg or 0.081 mmol/kg) or a large (0.10 ml/kg or 0.814 mmol/kg) dose, or by 6-hr inhalation exposure at a low (40 ppm) or a high (400 ppm) concentration. The concentrations of m-xylene and its major metabolite, m-methyl hippuric acid (m-MHA), were measured over time in the blood and urine, respectively. PB treatment, which increased the hepatic metabolism of m-xylene in vitro about sixfold, had a significant effect on the metabolism of inhaled m-xylene (decreased blood m-xylene concentration together with increased urinary excretion of m-MHA) only at a high exposure concentration (400 ppm). On the other hand, the enzyme induction had a significant effect on the metabolism of orally administered m-xylene either at a small (0.081 mmol/kg) or a large (0.814 mmol/kg) dose, due to the first-pass metabolism that plays a great role in this route. 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. However, in agreement with oral administration but in contrast to inhalation exposure, PB treatment increased the urinary excretion of m-MHA only shortly after intraperitoneal administration of m-xylene, with no significant increase occurring in the total amount of m-MHA excreted in the urine, despite the great difference in the blood m-xylene concentration between PB-treated and control rats.

Administration, Inhalation↗
PubMed1983

In vivo hydroxylation of 3H-acetanilide--evaluation of a new radiospirometric method in the rat.

The proposed in vivo methodology for the investigation of hydroxylation rates consists of of the i.v. administration of tritiated substrates and the collection of tritiated water (HTO) from exhaled air as a measure of HTO accumulation in body water. Specifically, HTO was assessed in exhaled water after i.v. administration of 3H-acetanilide. Over a wide range the half lives of accumulation of HTO in exhaled water (T50) were almost identical with the half lives of elimination of 3H-acetanilide in blood, evaluated by an inverse isotope dilution method (r = 0.96, N = 18). Average T50 amounted to 29 min in controls, was reduced to 20 min after enzyme induction by phenobarbital or 3-methylcholanthrene, and prolonged to 45, 46 and 66 min after bile duct ligation, portacaval shunt and a single dose of ethanol, respectively. It is concluded that the chosen pharmacokinetic approach corrects for the NIH-shift and the results adequately reflect changes in acetanilide hydroxylation related to enzyme induction or inhibition and to liver pathology.

Acetanilides↗
PubMed1997

Development of a screening method for anti-6 beta-hydroxycortisol antibody using an enzyme-linked immunosorbent assay (ELISA) and its applications.

An indirect enzyme-linked immunosorbent assay (ELISA) for the detection of anti-6 beta-hydroxycortisol (6 beta-OHC) antibody has been developed. After immunization of 6 beta-OHC protein conjugates in New Zealand White rabbits, specific polyclonal antibody to 6 beta-OHC was detected by ELISA in which the wells of microtiter plates were coated with 6 beta-OHC conjugated to protein. The rabbit anti-6 beta-OHC antibody titer was above 1:500,000 dilution. Cross-reactivity with other structurally related steroids such as cortisol hydrocortisone was less than 5%. The sensitivity of the polyclonal antibody was comparable to previous studies reported, and was within the accepted detection limit for 6 beta-OHC in man and in laboratory animals. The assay has a low detection limit of 1 ng/ml, an intraassay variation of 3.1% and an interassay variation of 5.2%. The application of the anti-6 beta-OHC-based-ELISA to detect urinary 6 beta-OHC was tested by measuring the concentration of 6 beta-OHC in man before and after enzyme induction by rifampicin treatment. The mean 24 h urine output of 6 beta-OHC in man subjects was 370 +/- 105 micrograms and 1350 +/- 201 micrograms before and after rifampicin administration, respectively. This polyclonal anti-6 beta-OHC antibody-based ELISA can be modified to detect mouse anti-6 beta-OHC IgG with equally good precision and specificity which should be useful in screening positive clones of a 6 beta-OHC IgG secreting mouse hybridoma currently being developed for detecting enzyme induction of CYP3A4 in man and laboratory animals.

Adult↗
PubMed1994

Changes in the concentration of serum alpha 1-acid glycoprotein in epileptic patients.

Factors leading to elevation of the serum level of alpha 1-acid glycoprotein (AAG), the principal binding protein of cationic drugs in the systemic circulation, were investigated in 142 epileptic patients receiving long-term therapy with carbamazepine (CBZ), phenytoin (DPH), phenobarbital (PB), or valproate (VPA). The mean serum activity of gamma-glutamyl transpeptidase (gamma-GTP), an indicator of enzyme induction, in the groups of patients receiving enzyme inducers such as CBZ, DPH, and/or PB was at least some 5-fold higher than in patients receiving VPA alone, which is well known to be a non-inducer. There was no significant difference in the mean serum level of AAG between the former and the latter groups, i.e. there was no correlation between AAG and gamma-GTP levels in serum, and it is unlikely that the enzyme inducing properties of CBZ, DPH and PB are associated with an increased level of AAG. The mean serum level of AAG in the patients with poorly controlled seizures was significantly higher than in those with well controlled seizures (0.81 vs. 0.56 milligram). The serum AAG level in individual patients changed in parallel with the frequency of seizures. The present results strongly suggest that elevation of serum AAG level in epileptic patients may not be associated with the enzyme-inducing activities of anticonvulsants, but with the epileptic seizures per se.

Adolescent↗
PubMed1990

The effect of hepatic enzyme inducers on busulfan neurotoxicity and myelotoxicity.

Anticonvulsants are commonly used empirically to prevent seizures in patients receiving high-dose busulfan in preparation for bone marrow transplantation. This study evaluates the effects of two anticonvulsants with enzyme-inductive properties, phenytoin and phenobarbital, and an enzyme inducer without anticonvulsant properties, Aroclor 1254, on the myelotoxicity and acute neurotoxicity of busulfan in a murine model. To assess the neuroprotective effects of these agents, we studied the effects of a single dose of 100 mg/kg i.p. busulfan, previously shown in this model to be uniformly lethal due to neurotoxicity. A significantly greater proportion of mice survived when pretreated with phenytoin or phenobarbital as compared with Aroclor 1254 pretreatment or an untreated control group. Busulfan myelotoxicity was studied in another group of mice treated with 135-150 mg/kg given in divided doses over 6 days. The proportion of animals surviving the otherwise myeloablative effects of this regimen were significantly improved by Aroclor 1254, high-dose phenytoin, and phenobarbital pretreatment. We conclude that anticonvulsants offer protection from the acute neurotoxicity of busulfan. However, these enzyme-inducing agents may reduce the myelosuppressive effects as well. These results suggest that an inducible enzyme system such as microsomal or glutathione S-transferases plays an important role in busulfan metabolism, warranting concern over concomitant administration of agents that either induce or inhibit these enzymes.

Animals↗
PubMed1983

The in situ assay of Candida albicans enzymes during yeast growth and germ-tube formation.

Conditions are described for the preparation of permeabilized cells of Candida albicans. This method has been used for the in situ assay of enzymes in both yeast cells and germ-tube forming cells. A mixture of toluene/ethanol/Triton X-100 (1:4:0.2, by vol.) at 15% (v/v) and 8% (v/v) was optimal for the in situ assay of glucose-6-phosphate dehydrogenase in yeast and germ-tube forming cells, respectively. The concentration of toluene/ethanol/Triton X-100 required for optimal in situ activity of other enzymes was influenced by the cellular location of the enzyme, growth phase and morphology. The membrane-bound enzymes (chitin synthase, glucan synthase, ATPase), cytosolic enzymes (glucose-6-phosphate dehydrogenase, isocitrate dehydrogenase, pyruvate kinase, phosphofructokinase, alkaline phosphatase, glucosamine-6-phosphate deaminase and N-acetylglucosamine kinase) and wall enzymes (beta-glucosidase and acid phosphatase) were measured and compared to the activity obtained in cell extracts. The pattern of enzyme induction and the properties of the allosteric enzymes phosphofructokinase and pyruvate kinase were measured in situ. Pyruvate kinase in situ was homotropic for phosphoenolpyruvate with a Hill coefficient of 1.9 and a S0.5 of 0.6 mM, whereas in cell extracts, it had a Hill coefficient of 1.9 and a S0.5 of 1.0 mM. The Km for ATP was 1.6 mM in cell extracts and 1.8 mM in permeabilized cells. In situ phosphofructokinase was homotropic for fructose 6-phosphate (S0.5 of 2.3 mM, Hill coefficient of 4.0). The kinetic properties of pyruvate kinase and phosphofructokinase measured in situ or in vitro were similar for both yeast cells and germ-tube forming cells.

Aldose-Ketose Isomerases↗
PubMed1986

Large theophylline requirements due to high theophylline clearance: verification by the antipyrine test.

An asthmatic patient required very high doses of theophylline (2.88 g/day by intravenous infusion) to maintain an adequate serum theophylline concentration (12 micrograms/ml). His cigarette smoking and concurrent treatment with phenytoin were suspected to have produced hepatic microsomal enzyme induction, causing unusually high theophylline clearance. The intravenous antipyrine test demonstrated an unusually short half-life (5.5 h) and high clearance (95 ml/min) of antipyrine, consistent with induced clearance of antipyrine. Formation of the 4-hydroxy metabolite of antipyrine was disproportionately induced. Thus the antipyrine test can be of clinical value for documenting hepatic microsomal enzyme induction in patients with low steady-state theophylline concentrations despite high maintenance doses.

Adult↗
PubMed1979

Chemical exposure and intestinal function.

The particular substances that are ingested by individuals are the consequence of their environmental, residential, and occupational exposures. The possible effects of these exposures on intestinal functions can be examined by the evaluation of in vivo or in vitro exposure followed by an in vivo and/or in vitro monitoring of effects. Several examples of the in vivo exposure and in vitro monitoring approach are presented to demonstrate the consequences of oral exposure to either a heavy metal (arsenic), or a herbicide contaminant (2,3,7,8-tetrachlorodibenzo-p-dioxin) or a jet fuel propellant (hydrazine) and the subsequent measurement of either a particular metabolic pathway, or a cell-specific enzyme induction or the development of brush border enzymes are presented.

Animals↗