Comparison of the metabolism of dodecanedioic acid in vivo in control, riboflavin-deficient and clofibrate-treated rats.
Intravenous administration of dodecanedioate (or hexadecanedioate) to anaesthetized rats resulted in the urinary excretion of medium-chain dicarboxylic acids (adipic, suberic and sebacic acids). In control animals, the recovery of infused dodecanedioate in the form of urinary medium-chain dicarboxylic acids corresponded to 30% of the infused dose (22 mumol/100 g body mass). This excretion was markedly increased in riboflavin-deficient rats (75% of the infused dose) while it was severely decreased in clofibrate-treated animals (less than 5%). The initial velocity of this process was similar in both control and riboflavin-deficient rats. In control animals, halving the infused dose of dodecanedioate to 11 mumol/100 g body mass resulted in a halving of the initial rate of the urinary appearance of medium-chain dicarboxylates, while doubling the amount of dicarboxylate administered to 44 mumol/100 g body mass did not further modify this velocity, but rather prolonged the duration of the excretion of the resulting products. In riboflavin-deficient and clofibrate-treated rats, the hepatic peroxisomal dicarboxylyl-CoA beta-oxidation activity measured as dicarboxylyl-CoA H2O2-generating oxidase and cyanide-insensitive dicarboxylyl-CoA-dependent NAD+ reduction was increased about threefold and tenfold, respectively. Dicarboxylyl-CoA synthetase activity was normal in the clofibrate-treated rat livers but was increased more than tenfold in the livers from the riboflavin-deficient animals. This work provides evidence that in the rat both mitochondria and peroxisomes are involved in the catabolism of dicarboxylates.
Draye
J P
JP
International Institute of Cellular and Molecular Pathology, Université Catholique de Louvain, Bruxelles, Belgium.
Veitch
K
K
Vamecq
J
J
Van Hoof
F
F
D000818:Animals; D002994:Clofibrate / Q000494:pharmacology*; D003998:Dicarboxylic Acids / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D007262:Infusions, Intravenous; D008297:Male; D008830:Microbodies / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012257:Riboflavin Deficiency / Q000378:metabolism*
D003998:Dicarboxylic Acids; C036836:dodecanedioic acid; D002994:Clofibrate