Urinary metabolites of L-threonine in type 1 diabetes determined by combined gas chromatography/chemical ionization mass spectrometry.
Metabolic profiling of urinary organic acids from patients with juvenile-onset (Type 1) diabetes mellitus have revealed significantly elevated levels of 2-hydroxybutyric and 4-deoxythreonic acids. To test the hypothesis that these metabolites, as well as 4-deoxyerythronic acid, are derived from L-threonine, stable isotope-labeled threonine was infused into an insulin-deficient dog and the incorporation of 13C into these metabolites was monitored by gas chromatography/mass spectrometry. Electron ionization was relatively insensitive, but positive chemical ionization with ammonia as the reactant gas gave both protonated molecules and [M + NH4]+ ions, which could be analysed by selected ion monitoring. The isotope-labeled species of 2-hydroxybutyric, 4-deoxyerythronic and 4-deoxythreonic acids were observed, but 13C was not incorporated into other organic acids. Thus, it is proposed that L-threonine is a precursor of these metabolites.
D000818:Animals; D002247:Carbon Isotopes; D003921:Diabetes Mellitus, Experimental / Q000652:urine*; D003922:Diabetes Mellitus, Type 1 / Q000652:urine*; D004285:Dogs; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D013912:Threonine / Q000652:urine*
D002247:Carbon Isotopes; D013912:Threonine