Comparison of in vitro carnitine and glycine conjugation with branched-side chain and cyclic side chain carboxylic acids in rats.
The substrate specificity for carnitine conjugation was examined using rat hepatocytes and kidney slices and compared with glycine conjugation which is a competitive pathway through the CoA thioester. For both hepatocytes and kidney slices, the best substrate for the camitine conjugate was cyclopropanecarboxylic acid followed by cyclobuthanecarboxylic acid (CBCA) and cyclohexanecarboxylic acid (CHCA). For the glycine conjugate, the best substrate was benzoic acid, with conjugation also occurring with CHCA and CBCA. These results suggest that carnitine transferase shows substrate specificity for cyclic side chain carboxylic acids of lesser carbon number, while glycine transferase shows inverse specificity. To compare directly the amounts of carnitine and glycine conjugates in the liver and the kidney, we estimated the endogenous amounts of carnitine and glycine and then multiplied the results by the production ratio of each conjugate. With respect to the enzyme activity per unit tissue weight, the kidney tended to show higher activities for both conjugates than the hepatocytes. This is the first report, to our knowledge, of the kidney having high carnitine conjugation activity. Cyclopentanecarboxylic acid (CPECA) was the least effective substrate for glycine and carnitine conjugates in both hepatocytes and kidney slices, CPECA may not readily undergo esterification with CoA. The branched-side chain carboxylic acids, such as pivalic acid (PA) and isobutylic acid, were also poor substrates for carnitine and glycine conjugates in rat hepatocytes and kidney slices.
Kanazu
T
T
Developmental Research Laboratories, Shionogi & Co. Ltd., Toyonaka, Osaka, Japan.
Yamaguchi
T
T
D000818:Animals; D001565:Benzoates / Q000378:metabolism; D019817:Benzoic Acid; D002087:Butyrates / Q000378:metabolism; D002264:Carboxylic Acids / Q000378:metabolism*; D002331:Carnitine / Q000378:metabolism*; D002478:Cells, Cultured; D003521:Cyclopropanes / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D058610:Isobutyrates; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001565:Benzoates; D002087:Butyrates; D002264:Carboxylic Acids; D003521:Cyclopropanes; D058610:Isobutyrates; C015766:cyclopropanecarboxylic acid; C020380:isobutyric acid; D019817:Benzoic Acid; D002331:Carnitine; D005998:Glycine