Search PubMed⌕ Search

Biomedical subjects

J N Smith

Publications and source records attributed to J N Smith.

At least 55 records · Page 3Linked to original sources

Metabolism of m-tert.-butylphenyl N-methylcarbamate in insects and mice.

The metabolism of m-tert.-butylphenyl N-methylcarbamate was studied in mice and five species of insects. Both the tert.-butyl group and the N-methyl group were hydroxylated. The major phenolic metabolite was m-(beta-hydroxy-tert.-butyl)phenol, which was identified by mass spectroscopy. Significant amounts of dihydroxy compounds were formed at a constant rate from the start of the enzymic oxidation process. The considerable species variation in the yields of the different types of oxidation products suggests that N-demethylation and oxidation of the tert.-butyl groups were catalysed by different enzymes. A microsomal NADPH-dependent enzyme also catalysed the splitting of the ester link in the insecticide.

Animals↗

The inhibition of 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (DDT) dehydrochlorinase and glutathione S-aryltransferase in grass-grub and housefly preparations.

The inhibition of DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane] dehydrochlorinase and glutathione S-aryltransferase by diphenylmethane and triphenylmethane derivatives was examined. Bis-(3,5-dibromo-4-hydroxyphenyl)methane and similar compounds were excellent inhibitors of both enzymes, but only DDT dehydrochlorinase was inhibited by compounds similar to bis-(N-dimethylaminophenyl)methane. Colour salts of the basic triphenylmethyl dyes were excellent inhibitors of both enzymes. All the inhibitors examined appeared to act by competition with glutathione for its binding site on the two enzymes.

Animals↗

The separation of multiple forms of housefly 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (DDT) dehydrochlorinase from glutathione S-aryltransferase by electrofocusing and electrophoresis.

Electrophoresis in a sucrose gradient at pH values between 5 and 8 separated housefly DDT [1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane] dehydrochlorinase into two major fractions. GSH S-aryltransferase under similar conditions migrated as a single peak of activity. Separation of housefly homogenates or partially purified enzyme preparations by electrofocusing in a natural pH gradient also showed the presence of multiple forms of DDT dehydrochlorinase.

Animals↗

Detoxications in peripatus. Sulphate, phosphate and histidine conjugations.

Phenols were detoxified in the Onycophoran Peripatoides novaezealandiae by conjugation with sulphuric acid and phosphoric acid, but no evidence for a glycoside detoxication could be found. [(14)C]Benzoic acid was metabolized in 24h to N(2)-benzoyl-l-histidine, which was identified by electrophoresis, chromatography and dilution analysis. Similar conjugates were formed with p-aminobenzoic acid and p-nitrobenzoic acid. In longer-duration experiments further unidentified metabolites were formed, two of which appeared to result from the further metabolism of the histidine conjugate.

Aminobenzoates↗

The metabolism of hexachlorocyclohexanes and pentachlorocyclohexenes in flies and grass grubs.

1. gamma-Hexachlorocyclohexane, gamma-pentachlorocyclohexene and delta-pentachlorocyclohexene were converted by houseflies and grass grubs into metabolites that had chromatographic properties identical with those of S-2,4-dichlorophenylglutathione. 2. The metabolism of gamma-hexachlorocyclohexane and the pentachlorocyclohexene isomers was negligible in newly emerged blowflies, but increased over the next 10 days. 3. The metabolism of both gamma-hexachlorocyclohexane and the pentachlorocyclohexene isomers was inhibited by simultaneous dosage with tetrabromophenolphthalein ethyl ester or Bromophenol Blue in both grass grubs and flies, but only the metabolism of pentachlorocyclohexenes in blowflies was stopped by simultaneous dosage with bis-(N-dimethylaminophenyl)methane. NN-Di-n-butyl-p-chlorobenzenesulphonamide had no effect on the metabolism of pentachlorocyclohexenes by blowflies. 4. The use of these inhibitors and colorimetric assays leads to the conclusion that a pentachlorocyclohexene is not a major intermediary metabolite of gamma-hexachlorocyclohexane in these insects.

Animals↗

Inhibitors of microsomal oxidations in insect homogenates.

1. Homogenates of insect tissues were assayed for enzymes capable of oxidizing p-nitrotoluene to p-nitrobenzoic acid. 2. Locust fat-body homogenate 10000g supernatant was an effective enzyme and required no added cofactors. 3. Homogenates of other insects or locust organs and 10000g sediment from locust fat-body were not active and inhibited microsomal oxidations carried out by locust fat-body or rabbit liver enzyme. 4. Inhibitory power was high in homogenates of whole flies and of fly heads or thoraces. 5. Inhibition appeared to involve both irreversible inactivation of enzyme and the removal of essential cofactors.

Acids↗

Enzymic oxidation of some alkylbenzenes in insects and vertebrates.

1. Oxidation rates of alkylbenzenes have been measured in 10000g supernatants of vertebrate livers, locust fat bodies and housefly abdomens. 2. Activity per g. of insect was greater in fly than locust preparations but both were of the same order as a range of vertebrate species. 3. Methyl groups of toluene and p-nitrotoluene were oxidized more rapidly than the side chains of higher homologues. 4. In the higher homologues hydroxylation occurred most readily at the alpha-methylene group and less readily at penultimate methylene and terminal methyl groups. 5. Oxidations in both vertebrates and insects were inhibited by piperonylbutoxide and similar synergists. 6. Oxidation activity was stimulated by pretreatment of rats, but not locusts, with phenobarbitone or 3,4-benzopyrene.

Animals↗

Oxidation of methyl groups by grass grubs and vertebrate liver enzymes.

1. Oxidation rates of p-nitrotoluene, p-acetamidotoluene and p-toluidine by intact grass grubs and vertebrate liver preparations were measured. 2. The effect of p-substitution in increasing the rate of conversion of the methyl into a carboxy group was in the order acetamido> nitro[unk] amino in mice and grass grubs. 3. Rates of oxidation of the N-methyl group in some alkylaryl N-methylcarbamates was measured and the effect of ring substituents in increasing the rate was in the order hydrogen> o-methyl or o-isopropyl> p-methyl or p-isopropyl> m-methyl or m-isopropyl. 4. Rates of oxidation of the N-methyl groups were similar to those of the p-substituted toluenes.

Acids↗