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This Article Full Text Full Text (PDF) 089011.Supplemental Data All Versions of this Article: clinchem.2007.089011v1 53/12/2169    most recent Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Wikoff, W. R. Articles by Siuzdak, G. Search for Related Content PubMed PubMed Citation Articles by Wikoff, W. R. Articles by Siuzdak, G. Related Collections Pediatric Clinical Chemistry Automation and Analytical Techniques

Metabolomics Identifies Perturbations in Human Disorders of Propionate Metabolism

¹ Department of Molecular Biology and The Center for Mass Spectrometry, The Scripps Research Institute, La Jolla, CA.
² Department of Pediatrics, University of California–San Diego, School of Medicine, La Jolla, CA.

^aAddress correspondence to these authors at: Department of Pediatrics, University of California–San Diego, School of Medicine, 9500 Gilman Dr., #0830, La Jolla, CA 92093-0830. Fax 619-543-3565; e-mail bbarshop{at}ucsd.edu or Department of Molecular Biology and The Center for Mass Spectrometry, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Fax 858-784-9496; e-mail siuzdak{at}scripps.edu.

Background: We applied untargeted mass spectrometry-based metabolomics to the diseases methylmalonic acidemia (MMA) and propionic acidemia (PA).

Methods: We used a screening platform that used untargeted, mass-based metabolomics of methanol-extracted plasma to find significantly different molecular features in human plasma samples from MMA and PA patients and from healthy individuals. Capillary reverse phase liquid chromatography (4 µL/min) was interfaced to a TOF mass spectrometer, and data were processed using nonlinear alignment software (XCMS) and an online database (METLIN) to find and identify metabolites differentially regulated in disease.

Results: Of the approximately 3500 features measured, propionyl carnitine was easily identified as the best biomarker of disease (P value 1.3 x 10^–18), demonstrating the proof-of-concept use of untargeted metabolomics in clinical chemistry discovery. Five additional acylcarnitine metabolites showed significant differentiation between plasma from patients and healthy individuals, and -butyrobetaine was highly increased in a subset of patients. Two acylcarnitine metabolites and numerous unidentified species differentiate MMA and PA. Many metabolites that do not appear in any public database, and that remain unidentified, varied significantly between normal, MMA, and PA, underscoring the complex downstream metabolic effects resulting from the defect in a single enzyme.

Conclusions: This proof-of-concept study demonstrates that metabolomics can expand the range of metabolites associated with human disease and shows that this method may be useful for disease diagnosis and patient clinical evaluation.

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				M. J. Bennett Untargeted Metabolomic Analysis Hits the Target Clin. Chem., December 1, 2007; 53(12): 2037 - 2039. [Full Text] [PDF]