Enantioselective analysis of ketone bodies in patients with beta-ketothiolase deficiency, medium-chain acyl coenzyme A dehydrogenase deficiency and ketonemic vomiting

Enantioselective multidimensional gas chromatography-mass spectrometry (ena ntio-MDGC-MS) is a valuable tool for the differentiation of enantiomers fro m complex matrices when present in trace amounts. The separation of chiral compounds provides further information on the diagnosis of diseases, and on normal and abnormal biochemical pathways. The formation of the normal urin ary metabolite 3-hydroxy-2-methylbutanoic acid (HMBA), excreted in abnormal ly high amounts in beta-ketothiolase deficiency, is not absolutely clarifie d. Metabolic pathways involving this metabolite are isoleucine catabolism, as well as presumably beta-oxidation of fatty acids and ketogenesis. The la tter two pathways are distinguishable in their enantioselectivity. Enantios elective analysis gives further information on interfering metabolic pathwa ys and the selectivity of the enzyme(s) forming HMBA. Different ratios of t he stereoisomers of HMBA in control urine samples and patients with beta-ke tothiolase deficiency were detected. Analogous to HMBA urinary 3-hydroxybut anoic acid (HBA) was investigated in several diseases. The formation of HBA and HMBA is expected to result from the same or similar metabolic pathways , Differences in the enantiomeric ratio of HMBA may originate from the enan tioselectivity of different enzyme systems. (C) 2000 Elsevier Science B.V. All rights reserved.