Substrate specificity for carnitine and glycine conjugation of branched side-chain and cyclic side-chain carboxylic acids in various experimental animals.
Substrate specificities for the carnitine and glycine conjugates of branched side-chain and cyclic side-chain carboxylic acids were examined using dog, rabbit, cynomolgus monkey, and squirrel monkey hepatocytes and kidney slices. For all tested samples, the substrate specificity for carnitine or glycine conjugation showed a similar tendency to those for rat experiments reported previously, that is, the best substrate for the carnitine conjugate was cyclopropanecarboxylic acid (CPCA), while that for the glycine conjugate was benzoic acid (BA), followed by cyclohexanecarboxylic acid (CHCA). With respect to carnitine conjugation for CPCA, rat hepatocytes showed the highest ability followed by dog, rabbit, and monkey hepatocytes. Rat kidney slices showed the highest carnitine conjugation ability, followed by rabbit, dog, and monkey kidney slices, in that order. With respect to glycine conjugation for BA, rabbit hepatocytes showed the highest ability, followed by rat and monkey hepatocytes. Dog hepatocytes have no or little glycine conjugate ability for the carboxylic acids studied here. Rabbit kidney slices showed the highest glycine conjugation ability followed by rat, dog, and monkey kidney slices.
Kanazu
T
T
Drug Metabolism & Pharmacokinetics, Development Research Laboratories, Shionogi & Co., Ltd, Osaka, Japan.
Yamaguchi
T
T