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Biomedical subjects

D V Parke

Publications and source records attributed to D V Parke.

At least 199 records · Page 11Linked to original sources
PubMed1977

The metabolism of cyclohexanecarboxylic acid in the isolated perfused rat liver.

1. Cyclohexanecarboxylic acid in isolated perfused rat livers was eliminated from the perfusion system by a first-order process. 2. After 6 h, 16% was excreted in bile as cyclohexylcarbonyl beta-D-glucuronide. The remainder was present in the perfusate as unchanged cyclohexanecarboxylic acid (10%), hippuric acid (50%), hexahydrohippuric acid (2%), 3,4,5,6-tetrahydrohippuric acid (2%), cyclohexylcarbonyl-beta-D-glucuronide (2-4%) and benzoic acid (1-2%). Six per cent of the dose was associated with the red blood cell present in the perfusion medium. 3. Unlike the whole animal, the isolated rat liver produced no detectable benzoyl glucuronide. 4. The identity and kinetics of production of the metabolites are consistent with a metabolic pathway previously proposed for cyclohexanecarboxylic acid and shikimic acid.

Animals↗
PubMed1976

Preparation of immobilized baker's-yeast glucose 6-phosphate dehydrogenase attached to modified sepharose and sephadex and a comparison of the properties of these preparations with those of the soluble enzyme.

1. Glucose 6-phosphate dehydrogenase (D-glucose 6-phosphate-NADP+ oxidoreductase, EC 1.1.1.49) from baker's yeast (Saccharomyces cerevisiae) was immobilized on CNBr-activated Sepharose 4B with retention of about 3% of enzyme activity. This uncharged preparation was stable for up to 4 months when stored in borate buffer, pH7.6, at 4 degrees C. 2. Stable enzyme preparations with negative or positive overall charge were made by adding valine or ethylenediamine to the CNBr-activated Sepharose 4B 30min after addition of the enzyme. 3. These three immobilized enzyme preparations retained 40-60% of their activity after 15 min at 50 degrees C. The soluble enzyme is inactivated by these conditions. 4. The soluble enzyme lost 45 and 100% of its activity on incubation for 3h at pH6 and 10 respectively. The three immobilized-enzyme preparations were completely stable over this entire pH range. 5. The pH optimum of the positively and negatively charged immobilized-enzyme preparations were about 8 and 9 respectively. The soluble enzyme and the uncharged immobilized enzyme had an optimum pH at about 8.5 6. Glucose 6-phosphate dehydrogenase immobilized on CNBr-activated Sephadex G-25 was unstable, as was enzyme attached to CNBr-activated Sepharose 4B to which glycine, asparitic acid, valine or ethylenediamine was added at the same time as the enzyme.

Buffers↗
PubMed1976

The effects of benzopyrene and safrole on biphenyl 2-hydroxylase and other drug-metabolizing enzymes.

A study was made of the nature and specificity of the increase in biphenyl 2-hydroxylase activity after preincubation of liver microsomal preparations with various carcinogens in vitro. This enhancement of enzyme activity in vitro was investigated in mouse, hamster and rat, and although the rat appears to be atypical in the variation of the pattern of 2- and 4-hydroxylation with age, similar enhancements were detectable in each species examined. An increase in biphenyl 2-hydroxylase activity was apparent 2h after intraperitoneal administration of safrole or benzopyrene to mature Wistar albino rats and appeared to be similar in nature to that observed after preincubation of liver microsomal preparations with the same chemical in vitro. Investigation of other drug-metabolizing enzyme systems suggests that the enhancing effects of carcinogens in vitro are specific for biphenyl 2-hydroxylase. No correlation between the enhancement of biphenyl 2-hydroxylase and inhibtion of biphenyl 4-hydroxylase was apparent.

Acetone↗
PubMed1976

The effect of some glucocorticoids on hepatic microsomal hydroxylation in the rat and hamster.

The effect of some glucocorticoids on hepatic microsomal biphenyl and aniline hydroxylations were investigated in rat and hamster. Steroids were either added to the standard incubation mixture or given as a single dose intraperitoneally before preparation of the liver microsomes for enzyme determination. The addition of steroids in vitro enhanced biphenyl-2-hydroxylation activity in hepatic microsomes of rat but not of hamster and the most pronounced effect was obtained with betamethasone. A similar species difference in the effects of betamethasone on this enzyme was also observed after administration of a single dose of the steroid in vivo.

Aniline Hydroxylase↗
PubMed1976

The effect of allyl compounds on hepatic microsomal mixed function oxidation and porphyrogenesis.

The activities of 5-aminolaevulinate (5-ALA) synthetase and of various microsomat drug-metabolising enzymes have been determined in the livers of rats pretreated with different drugs and chemicals containing the allyl group. Safrole, isosafrole and secobarbital gave rise to slight increases in 5-ALA synthetase, whereas alclophenac and triallyl cyanurate almost doubled the enzyme activity and the known porphyrogenic agents, allylisopropylacetamide (AIA) and allobarbital caused increases of 1.5- and 2.5-fold, respectively. Allobarbital induced the microsomal drug-metabolising enzymes while secobarbital had only a weak effect and alclophenac and triallyl cyanurate had no effect at all. From these results it is suggested that induction of the synthesis of cytochrome P-450 is not rate dependent on the synthesis haem and induction of porphyrin biosynthesis.

5-Aminolevulinate Synthetase↗
PubMed1976

Effect of protein-energy nutrition on the activity of hepatic microsomal drug-metabolizing enzymes in growing rats.

Male Wistar weanling rats were divided into three groups and fed one of the following diets for 7, 14 and 28 days: a control diet (21% protein) fed ad libitum, a low protein diet fed ad libitum (the control diet diluted to contain 7% protein by the addition of starch) or an energy and protein restricted diet (control diet fed to provide protein intake equal to that consumed by the low protein group). The activity of glucoronyl transferase was depressed by energy restriction and cytochrome P-450 was depressed by the low protein-ad libitum energy diet compared to controls. In the animals fed the low protein diet with ad libitum energy for 14 or 28 days, the rise in the activity of biphenyl 4-hydroxylase per g liver was sufficient to compensate for the lower liver weight so that the absolute amount of enzyme activity per liver was the same as in the controls. Due to adaptive response of the enzyme to the low protein diet, the activity of biphenyl 4-hydroxylase per g liver was higher than in the controls in animals fed a protein-free diet. It is concluded that the adaptive response of biphenyl 4-hydroxylase was possibly mediated by corticosteroids and was not due to a change in the conformation of the enzyme.

Animals↗
PubMed1976

Gastrointestinal absorption of carbenoxolone in the rat determined in vitro and in situ: deviations from the pH-partition hypothesis.

The absorption of [14C] carbenoxolone from everted rat ileum in vitro and from rat stomach and ileum in situ has been examined. The rate of its mucosal to serosal transfer in vitro increases as pH increases from 5 to 8 whereas the amount bound to ileum tissue decreases with increased pH; absorption closely parallels the drug's solubility. The uptake of carbenoxolone in situ is bi-exponential and the rate constants for the two processes, have been calculated. Absorption in situ, and biliary excretion, of the drug increases with increasing pH from 5.0 to 7.4. Tissue binding to the ileum in situ is not dependent on pH except below pH 5.0 when extensive tissue accumulation of carbenoxolone occurs because of its low solubility. Tissue binding to the stomach increases markedly with decrease of pH from 7.4 to 6.5 and at pH 6.5 is 80 times greater than binding to the intestine. The rate of absorption from the stomach, at pH 6.5-7.4, was much less than that from the intestine in situ. When allowance is made for the binding of carbenoxolone to the stomach, contrary to the pH-partition hypothesis, correlation is apparent between its absorption and the amount present in the ionized form.

Animals↗
PubMed1976

The binding of trichlorofluoromethane and other haloalkanes to cytochrome P-450 under aerobic and anaerobic conditions.

1. Trichlorofluoromethane and other haloalkanes interact with hepatic microsomal cytochrome P-450 to give type I spectra under aerobic conditions. 2. Anaerobically, CCl3F, CCl2F. CClF2 and CCl4 interact to give peaks at approx. 420 nm and 455 nm; the other haloalkanes gave peaks at approx. 420 nm only. The formation of the 452 nm peak for CCl3F was time-dependent, and dependent on substrate concentration. 3. Iso-octane extraction of the microsomal preparation increased the magnitude of spectral interaction under reducing conditions but not its rate of formation. Phenobarbitone pretreatment increased the magnitude of the spectral interaction; 3-methylcholanthrene pre-treatment had no effect on the magnitude of the 452 nm peak but decreased its rate of formation. 4. It is suggested that the 452 nm peak represents the interaction of a reactive species formed from CCl3F with the Fe2+ of the haem of reduced cytochrome P-450.

Aerobiosis↗
PubMed1975

Mitochondrial enzyme pathways and their possible role during curing.

The velocity of oxidation of exogenous ferrocytochrome c by nitrite under anaerobic conditions in the presence of skeletal muscle mitochondria is dependent upon pH over at least the range 5.6-6.7, increasing markedly as the pH is lowered. A product of the reaction is the complex formed between nitric oxide and ferricytochrome c. At levels up to 20 mM, nitrite inhibits aerobic cytochrome oxidase action; at higher concentrations, however, a partial resuscitation of the oxidation of ferrocytochrome c occurs, the enhancement of reaction velocity being considerably greater at pH 6.0 than at 6.5. Mitochondrial respiration is also inhibited by nitrite but no similar resurgence was, however, observed and thus the oxidation of ferrocytochrome c by high levels of nitrite is considered to be a direct non-enzymic action. Under anaerobic conditions, the rate of increase of the velocity constant of the oxidation of ferrocytochrome c with nitrite concentration in the presence of muscle mitochondria similarly decreased with rise of pH over the same range. The permeability of the muscle mitochondrion to nitrire has been demonstrated by swelling studies and by the rapid conversion of endogenous ferrocytochrome a3 into its nitrosyl-derivative. Over longer periods of anaerobic incubations of mitochondria with nitrite, oxidation of endogenous cytochromes occurs with the formation of nitrosylferricytochrome c. Above a nitrite concentration of 0.3 mM, the mitochondrial enzyme system probably involved is increasingly inhibited but by a concentration of 30 mM a direct non-enzymic oxidation has intervened. Commercial vacuum packed bacons were examined by electron microscopy. Mitochondria were clearly recognisable although they contained fewer cristae than those observed in fresh meat.

Electron Transport Complex IV↗