Formation of n-hexanedioic acid from hexadecanoic acid by an initial ω oxidation in ketotic rats

Abstract

1. 1. Urine samples from normal and ketotic rats (streptozotocin-induced ketosis) have been analysed for dicarboxylic acids using gas-liquid chromatography and mass spectrometry. 2. 2. Normal rats were found to excrete small amounts of hexanedioic acid (0.2–0.5 μmoles/24 h) and only traces of octanedioic acid (less than o.1 μmoles/24 h) in the urine. Ketotic rats, on the other hand, excreted considerable quantities of both hexanedioic and octanedioic acid (up to 8.7 and 1.8 μmoles/24 h, respectively) in addition to large amounts of 3-hydroxybutyrate. 3. 3. There was a positive correlation between the excretion of hexanedioic and octanedioic acid and the excretion of 3-hydroxybutyrate. 4. 4. Urine samples from two ketotic rats given [1- 14C]- or [16- 14C]hexadecanoic acid, respectively, have been analysed for radioactive label in the hexanedioic acid by a procedure including extractions, thin-layer chromatography and preparative gas chromatography. Equal amounts of radioactivity (about 0.02% of the injected dose) were found in the hexanedioic acid fraction from both rats. 5. 5. These results indicate that long-chain fatty acids may be precursors of the hexanedioic and octanedioic acid excreted in urine during ketosis, and, furthermore, that most or all of the dicarboxylic acids derived from long-chain fatty acids are formed by an initial co oxidation followed by β oxidations.