The biological origin of ketotic dicarboxylic aciduria. II. In vivo and in vitro investigations of the beta-oxidation of C8-C16-dicarboxylic acids in unstarved, starved and diabetic rats.
The beta-oxidation of C8-C16-dicarboxylic acids to short-chain dicarboxylic acids was investigated in vivo and in rat liver homogenate. The beta-oxidation in vivo was evaluated from the excretions of C6-C10-dicarboxylic acids in urine from rats given C8-C16-dicarboxylic acids. Correspondingly, the beta-oxidation in vitro was determined from the rise in concentration of C6-C10(12)-dicarboxylic acids in the postnuclear (600Xg) fraction of rat liver homogenates incubated with C8-C16-dicarboxylic acids. The results showed that C10-C14-dicarboxylic acids were far better substrates for beta-oxidation than were C8- and C16-dicarboxylic acids. In particular, hexadecanedioic acid could only be beta-oxidized to a minor degree, and, in contrast to the other dicarboxylic acids, it was toxic for starved rats. The activity of the lipid metabolism (unstarved, starved and diabetic ketotic rats) was of decisive significance for the quantity and pattern of the C6-C10-dicarboxylic acids present both in vivo and in vitro, since adipic acid was increased and sebacic acid decreased with increasing lipid catabolism, i.e. the adipic: sebacic acid ratio increased with increasing rates of beta-oxidation. On comparison with earlier investigations on the chain-length dependency of the omega-oxidation of monocarboxylic acids it was concluded that the biological origin of the ketotic C6-C8 -dicarboxylic aciduria is C10-C14-monocarboxylic acids, and that an elevated beta-oxidation rate is important for the formation of C6-C8-dicarboxylic aciduria.
D000138:Acidosis / Q000652:urine*; D000818:Animals; D003998:Dicarboxylic Acids / Q000378:metabolism* / Q000652:urine; D005260:Female; D007662:Ketosis / Q000652:urine*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013217:Starvation; D013329:Structure-Activity Relationship
D003998:Dicarboxylic Acids