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Am J Physiol Gastrointest Liver Physiol 256: G680-G688, 1989;
0193-1857/89 $5.00
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AJP - Gastrointestinal and Liver Physiology, Vol 256, Issue 4 680-G688, Copyright © 1989 by American Physiological Society


ARTICLES

Rat liver metabolism of dicarboxylic acids

J. Vamecq, J. P. Draye and J. Brison
Laboratorie de Chimie Physiologique, University of Louvain, Brussels, Belgium.

Recently, we demonstrated in rat liver that dicarboxylic acids containing more than five carbons can be activated by a microsomal dicarboxylyl-CoA synthetase (J. Vamecq, E. de Hoffmann, and F. Van Hoof. Biochem. J. 230: 683-693, 1985). The products of this reaction, dicarboxylyl-CoA esters, were found to be substrates for an H2O2-generating dicarboxylyl-CoA oxidase. In the present work we report that 1) the catalytic center or the essential domains of dicarboxylyl-CoA synthetase are located at the cytosolic aspect of the endoplasmic reticulum membrane; 2) dicarboxylyl-CoA oxidase is optimally active on dodecanedioyl-CoA and is a peroxisomal enzyme; 3) cyanide-insensitive dodecanedioyl-CoA oxidation (NADH production) is catalyzed by rat liver homogenates. Cell fractionation studies disclose that, similar to dodecanedioyl-CoA oxidase (H2O2 production), the cyanide-insensitive dodecanedioyl-CoA oxidizing activity also belongs to peroxisomes; 4) a dodecanedioyl-CoA oxidoreductase reaction can be assayed by the dichlorphenolindophenol procedure in rat liver homogenates, and the activity is abundant in peroxisomal, mitochondrial, and soluble fractions; 5) by contrast with monocarboxylyl-CoA esters, the dicarboxylyl-CoAs are apparently not substrates for mitochondrial fatty acid oxidation; however, the use of dicarboxylylcarnitine esters as direct substrate for mitochondria suggests the existence of an active beta-oxidation of dicarboxylates in these organelles, which is further confirmed by experiments in which mitochondria are permeabilized with digitonin; 6) the in vivo oxidation of infused dodecanedioic acid results in a rapid appearance in urine of medium-chain dicarboxylic acids, with only 30-50% of the infused dose recovered in urine.


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G. Liu, B. Hinch, and A. D. Beavis
Mechanisms for the Transport of alpha ,omega -Dicarboxylates through the Mitochondrial Inner Membrane
J. Biol. Chem., October 11, 1996; 271(41): 25338 - 25344.
[Abstract] [Full Text] [PDF]




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