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Biomedical subjects

C T Bedford

Publications and source records attributed to C T Bedford.

11 recordsLinked to original sources

Reactions of pentachlorophenol with laccase from Coriolus versicolor.

Laccase, purified from Coriolus versicolor, removed pentachlorophenol (PCP) from solution at pH 5, depending on initial PCP concentration and amount of laccase. With 100 units of laccase, 100% of 25 microg ml(-1) PCP and 60% of 200 microg ml(-1) PCP were removed respectively over 72 h. No free chloride was released in the reaction. In reaction with 100 microg PCP, products were primarily polymers (about 80,000 MW) with only 2-3 pg of o- and p-chloranils formed. Polymers were stable to acid hydrolysis and no release of PCP, or other low-molecular-weight products, was detected over several weeks. Laccase has a potential use in the biotreatment of aqueous effluents containing PCP, with polymerised products being removed from solution due to their high molecular weight.

Biodegradation, Environmental↗

Glucuronic acid conjugates.

The methods of assay in body fluids of 1-beta-alkyl, 1-beta-phenyl and 1-beta-acyl glucuronic acids ("glucuronide conjugates") have been reviewed. Most of the 78 references cited (from the literature of the period 1990-1997) concern the glucuronide conjugates of drug metabolites, and these have been considered, for reasons of accessibility, within sections of individual drug classes such as analgesics, anti-cancer agents and opioids. Other glucuronide conjugates are considered under "miscellaneous compounds". A few gas chromatography and capillary electrophoresis methods are described, but the major technique of assay (62 citations) is reversed-phase high-performance liquid chromatography.

Chromatography, Gas↗

Structure-activity studies of sulfate transfer: the hydrolysis and aminolysis of 3'-phosphoadenosine 5'-phosphosulfate (PAPS).

The pH-rate profile for the hydrolysis of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) in aqueous solution has been measured. Comparison with other data suggests that hydrolysis occurs by almost complete unimolecular elimination of sulfur trioxide, with weak involvement of a molecule of water in the transition state. The catalytic power (kcat/kuncat) of the sulfotransferases is estimated to be in the order of 10(10)-10(12). Amines--exemplified by morpholine--react spontaneously with PAPS in water at 39 degrees C by attack at both sulfuryl and (5')phosphoryl groups in a ratio of 2:3. The mechanism of activation of the coenzyme, PAPS, by the sulfotransferases that catalyse N-sulfation must involve suppression of its native N-phosphorylating reactivity and specific enhancement of its N-sulfating reactivity. Studies of the aminolysis of the coenzyme in aprotic solvent-water mixtures suggest how this might be accomplished.

Amines↗

An example of the oxidative de-esterification of an isopropyl ester. Its role in the metabolism of the herbicide flampropisopropyl.

1. Two mammalian metabolites of the herbicidal ester, flamprop-isopropyl (BARNON), have been characterized as products of omega-hydroxylation of the isopropoxycarbonyl grouping (-CO2 CHMe 2). 2. Hydroxylation at the methine group of this moiety, to afford an unstable lactol (-CO2C(OH)Me2) and thence the corresponding carboxylic acid also appears to occur. On the basis of experiments with rat liver microsomes, this pathway to the acid may be as important as the esterase-catalysed route. 3. Biomimetic oxidation studies with peroxytrifluoroacetic acid of a simple model of the herbicide (isopropyl acetate) have provided confirmation of the feasibility of the novel biotransformation.

Anilides↗

The metabolic fate of endrin in the rabbit.

1. [14C]Endrin, administered orally to rabbits, is excreted in the faeces as unchanged endrin (50% of that administered) and in the urine as a mixture of polar metabolites. 2. The major biotransformation is hydroxylation at the methylene bridge (C-12) to yield anti-12-hydroxyendrin. syn-Hydroxylation at C-12 also occurs. 3. The hydroxylated metabolites are excreted mainly as their sulphate conjugates. 4. Glucuronide conjugates are also excreted. anti-12-Hydroxyendrin is rapidly conjugated in vitro on incubation with rabbit liver microsomal glucuronyl transferase and UDPGA. 5. Comparative aspects of the metabolism of endrin in rats and rabbits are discussed.

Administration, Oral↗