title: Formation and degradation of dicarboxylic acids in relation to alterations in fatty acid oxidation in rats.
abstract: Dicarboxylic acids are excreted in urine when fatty acid oxidation is increased (ketosis) or inhibited (defects in beta-oxidation) and in Reye's syndrome. omega-Hydroxylation and omega-oxidation of C6-C12 fatty acids were measured by mass spectrometry in rat liver microsomes and homogenates, and beta-oxidation of the dicarboxylic acids in liver homogenates and isolated mitochondria and peroxisomes. Medium-chain fatty acids formed large amounts of medium-chain dicarboxylic acids, which were easily beta-oxidized both in vitro and in vivo, in contrast to the long-chain C16-dicarboxylic acid, which was toxic to starved rats. Increment of fatty acid oxidation in rats by starvation or diabetes increased C6:C10 dicarboxylic acid ratio in rats fed medium-chain triacylglycerols, and increased short-chain dicarboxylic acid excretion in urine in rats fed medium-chain dicarboxylic acids. Valproate, which inhibits fatty acid oxidation and may induce Reye like syndromes, caused the pattern of C6-C10-dicarboxylic aciduria seen in beta-oxidation defects, but only in starved rats. It is suggested, that the origin of urinary short-chain dicarboxylic acids is omega-oxidized medium-chain fatty acids, which after peroxisomal beta-oxidation accumulate as C6-C8-dicarboxylic acids. C10-C12-dicarboxylic acids were also metabolized in the mitochondria, but did not accumulate as C6-C8-dicarboxylic acids, indicating that beta-oxidation was completed beyond the level of adipyl CoA.
authors.affiliation: Department of Medicine A, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: P B
authors.initials: PB
authors.lastname: Mortensen
mesh_terms: D000818:Animals; D002264:Carboxylic Acids / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008830:Microbodies / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002264:Carboxylic Acids; D003998:Dicarboxylic Acids; D005227:Fatty Acids