Among the urinary metabolites of dodecylcyclohexane or cyclohexylacetic acid, the glycine conjugate of 1-hydroxy-cyclohexylacetic acid was identified and its origin studied, using cyclohexylacetic acid as the starting molecule, as it results from beta-oxidation of cyclohexyldodecanoic acid produced by terminal oxidation of the alkyl chain of the cycloparaffin. Three hypotheses were tested: (a) hydroxylation by the liver microsomal mixed-function oxidases involved in detoxication mechanisms; (b) hydroxylation by a cyt. P450-containing mitochondrial hydroxylase; and (c) beta-oxidation blockade after the reaction catalyzed by enoyl-CoA-hydratase. Liver microsomal or mitochondrial fractions were prepared and incubated in the presence of [14C] cyclohexylacetic acid, glucose-6-phosphate dehydrogenase and a NADPH-producing system. On the other hand, mitochondria were incubated in a suitable respiratory medium with or without cofactors required for ATP production. The reaction products were extracted and analyzed by thin layer radiochromatography and radio gas chromatography. Evidence is given that hydroxylation of cyclohexylacetic acid in position 1 is a mitochondrial step requiring activation in the acyl-CoA form and results from beta-oxidation blockade, the cyclohexane ring hindering hydroxyacyl-CoA-dehydrogenase action.

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