title: 3-, 6- and 7-hydroxyoctanoic acids are metabolites of medium-chain triglycerides and excreted in urine as glucuronides.
abstract: Three new metabolites of medium-chain fatty acid oxidation, 3-, 6- and 7-hydroxyoctanoyl beta-D-glucuronide, were identified in the urine of six infants who were fed a diet enriched in medium-chain triglycerides (MCT). Glucuronides were extracted from the urine by organic solvent extraction with ethyl acetate and by solid-phase extraction on Sep-Pak C18 cartridges. The compounds of interest were also purified from the organic solvent extract by preparative one-dimensional thin-layer chromatography. Cleavage of the glucuronides was achieved by either alkaline hydrolysis or enzymatic hydrolysis with beta-D-glucuronidase. The analyses of the trimethylsilylated derivatives were performed both by gas chromatography with flame ionization detection (GC/FID) and by gas chromatography/mass spectrometry (GC/MS). The structure of the hydroxyoctanoic acids was proved by comparison of their mass spectra with those of reference substances. Authentic 6-hydroxyoctanoic acid was synthesized. The presence of 6-hydroxyoctanoyl glucuronide shows that in addition to beta-oxidation, omega-oxidation and (omega-1)-hydroxylation, medium-chain fatty acids can be oxidized at the omega-2 position. The conjugation of medium-chain hydroxy-monocarboxylic acids with glucuronic acid has not been described in humans before.
authors.affiliation: University Children's Hospital, Het Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands.
authors.forename: C C
authors.initials: CC
authors.lastname: Costa
authors.forename: L
authors.initials: L
authors.lastname: Dorland
authors.forename: M
authors.initials: M
authors.lastname: Kroon
authors.forename: I
authors.initials: I
authors.lastname: Tavares de Almeida
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
authors.forename: M
authors.initials: M
authors.lastname: Duran
mesh_terms: D002210:Caprylates / Q000652:urine*; D002855:Chromatography, Thin Layer; D004032:Diet; D005410:Flame Ionization; D008401:Gas Chromatography-Mass Spectrometry; D005965:Glucuronates / Q000652:urine; D006801:Humans; D006868:Hydrolysis; D007223:Infant; D010084:Oxidation-Reduction; D014280:Triglycerides / Q000652:urine*
chemical_list: D002210:Caprylates; D005965:Glucuronates; D014280:Triglycerides; C026717:7-hydroxyoctanoic acid; C101941:6-hydroxyoctanoic acid; C101940:3-hydroxyoctanoic acid