Urinary 3-hydroxyadipic acid 3,6-lactone: structural identification and effect of fasting in adults and children.
Increased urinary excretion of medium-chain dicarboxylic acids is a general feature of disordered fatty acid metabolism. The physiological role of the metabolic pathways involved in dicarboxylic acid production has been a subject of controversy. In the present investigation, the existence of 3-hydroxyadipic acid 3,6-lactone, possibly representing a metabolic intermediate in the beta-oxidation of adipic acid to succinic acid, has been demonstrated. The identity of this compound was established by electron-impact mass spectrometry of its trimethylsilyl derivative and by comparison with synthetic authentic samples. 3-Hydroxyadipic acid 3,6-lactone is present in almost every urine sample we have examined. In the nonfasting state, urinary concentrations of 0.9 +/- 0.5 micrograms/mg creatinine were observed in the adults. During fasting, the urinary excretion of this compound increased with time. It reached 19.1 +/- 8.5 micrograms/mg creatinine by the end of the third day. The responses in children were even higher; urinary concentrations of 82 +/- 50 micrograms/mg creatinine were observed by the end of 36 hours. The urinary excretion of the lactone is closely correlated (r2 = 0.8) with that of adipic acid, an indicator of fatty acid omega-oxidation activity. Non-ketotic dicarboxylic aciduria appears to vary in different defects based on the ratio of urinary lactone to adipic acid.
Tserng
K Y
KY
Veterans Administration Medical Center, Cleveland, OH 44106.
Jin
S J
SJ
Hoppel
C L
CL
Kerr
D S
DS
Genuth
S M
SM
D000272:Adipates / Q000138:chemical synthesis / Q000652:urine*; D000328:Adult; D015415:Biomarkers / Q000652:urine*; D002264:Carboxylic Acids / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D002849:Chromatography, Gas; D005215:Fasting; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007202:Indicators and Reagents; D007783:Lactones / Q000138:chemical synthesis / Q000652:urine*; D008875:Middle Aged
D000272:Adipates; D015415:Biomarkers; D002264:Carboxylic Acids; D005227:Fatty Acids; D007202:Indicators and Reagents; D007783:Lactones; C060196:3-hydroxyadipic acid 3,6-lactone