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Biomedical subjects

J Capdevila

Publications and source records attributed to J Capdevila.

At least 73 records · Page 4Linked to original sources
PubMed1982

Cytochrome P-450-dependent oxygenation of arachidonic acid to hydroxyicosatetraenoic acids.

Arachidonic acid is oxidized by a NADPH-dependent oxygenase of rat liver microsomes to a number of oxygen-containing products, which can be resolved by HPLC. Several of these products have been purified and characterized. They exhibit an absorbance in the UV region of the spectrum that has a maximum at approximately 235 nm, indicative of the presence of a conjugated diene function. Mass spectral analysis of the trimethylsilyl ether derivatives of the methyl esters of the hydrogenated and nonhydrogenated metabolites shows that they are the 9-, 11-, 12-, and 15-monohydroxy derivatives of arachidonic acid, the hydroxyicosatetraenoic acids (HETEs). Their UV absorbance and chromatographic properties suggest that these products possess cis,transdiene geometry characteristic of HETEs isolated from other mammalian sources. THe isolation of these isomeric HETEs suggests that cytochrome P-450 may play a role in the oxidative metabolism of arachidonic acid to physiologically and pharmacologically important hydroxylated unsaturated fatty acids.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1981

Liver microsomal cytochrome P-450 and the oxidative metabolism of arachidonic acid.

Arachidonic acid is oxidatively metabolized by rat liver microsomes at a rate of approximately 5 nmol per min per mg of protein at 25 degrees C. This reaction is dependent on the presence of NADPH and oxygen. Studies with various inhibitors indicate a role for membrane-bound cytochrome P-450 in the transformation of arachidonic acid to a mixture of hydroxy acid derivatives. The stoichiometry of the reaction conforms to that of a monooxygenase reaction--i.e., one mole of NADPH is oxidized per mole of oxygen utilized--suggesting a reaction mechanism different from that proposed for lipid peroxidation reactions. No evidence for the formation of prostaglandin-like metabolites was obtained. The diene character of some of the metabolites formed suggests another role for cytochrome P-450--i.e., participation in hydrogen abstraction reactions for the activation of various substrates.

Animals↗
PubMed1979

The metabolic activation of benzo(a)pyrene and 9-hydroxybenzo(a)pyrene by liver microsomal fractions.

A rat liver microsome-mediated bacterial mutagenicity test showed 9-hyroxybenzo(a)pyrene to be significantly more effective as a pre-mutagen than benzo(a)pyrene. Experiments measuring the ability of these compounds to be metabolically activated to moieties that alkylate exogenous DNA demonstrated that 9-hydroxybenzo(a)pyrene was almost six times more effective than benzo(a)pyrene itself. Addition of trichloropropene-2,3-oxide to the reaction mixture enhanced the mutagenicity and DNA alkylation by benzo(a)pyrene but had little or no effect on the 9-hydroxybenzo(a)pyrene-mediated mutagenicity and alkylation. On the other hand, 7,8-benzoflavone inhibited the microsome-mediated mutagenicity and DNA alkylating activity of both hydrocarbons.

Alkylation↗
PubMed1979

Diagnostic value of leucocytic acid-phosphatase isoenzymes in determining cytological types of non-lymphoid acute leukaemias.

The normal isoenzymatic pattern of leucocytic acid-phosphatase based on the study of 150 haematologically normal individuals is reported. The different pathologic patterns of the leucocytic acid-phosphatase isoenzymes occurring in non-lymphoblastic acute leukaemias are presented and correlated with the subdivisions of acute leukaemias established by the French-American-British (FAB) Co-operative Group. This study is considered to be especially useful in identifying pure acute monocytic leukaemias corresponding to subtype M5 of the FAB as well as acute erythraemias with unusual cytological and cytochemical features.

Acid Phosphatase↗
PubMed1975

The metabolism of benzo(alpha)pyrene in isolated rat liver cells.

Isolated rat liver cells catalyze the metabolism of benzo(alpha)pyrene (BP) with the resulting formation of phenols, dihydrodiols, and conjugates. The rate of the primary oxidative step in the process was similar to that catalyzed by isolated rat liver microsomes in the presence of a reduced nicotinamide adenine dinucleotide phosphate-generating system and responded similarly to various inhibitors, including 2-diethylaminoethyl-2,2-diphenylvalerate, metyrapone, alpha-naphthoflavone, and hexobarbital. The level of cytoplasmic, reduced nicotinamide adenine dinucleotide phosphate was not rate limiting in liver cells isolated from either fed or fasted animals. The conjugates and dihydrodiols formed were readily excreted, whereas low concentrations of phenols accumulated intracellularly. The pattern of metabolites of BP was the same in isolated rat liver cells and in the isolated perfused rat liver. 3-Methylcholanthrene treatment of the rats caused a marked increase in cellular BP metabolism as well as in cytochrome P-450 concentration. The induced hemoprotein revealed characteristics similar to those previously established with isolated liver microsomes, i.e., increase in high-spin form, enhanced affinity for BP as revealed by a lower Michaelis constant, and sensitivity to the inhibitory action of alpha-naphthoflavone. After 3-methylcholanthrene treatment, phenols and dehydrodiols constituted a larger percentage of the total metabolites, indicating a more pronounced stimulation of the oxidative than of the conjugative step of BP metabolism by induction, and the dihydrodiols now tended to accumulate intracellularly.

Animals↗