Quantitative measurement of plasma 3-hydroxyisovaleryl carnitine by LC-MS/MS as a novel biomarker of biotin status in humans

  • Anal Chem. 2010 May 15;82(10):4140-4. doi: 10.1021/ac1003213.
Thomas D Horvath  1 ,  Shawna L Stratton ,  Anna Bogusiewicz ,  Lindsay Pack ,  Jeffery Moran ,  Donald M Mock
Affiliations
  • 1. Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, Arkansas 72205, USA.
PMID: 20397702 DOI: 10.1021/ac1003213
Abstract

An increased plasma concentration of 3-hydroxyisovaleryl carnitine (3HIA-carnitine) results from impairment in the leucine catabolic pathway at the conversion of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA. The impairment is caused by reduced activity of the biotin-dependent enzyme 3-methylcrotonyl-CoA carboxylase. Here, we describe an LC-MS/MS method for the quantitation of 3HIA-carnitine in plasma and present preliminary evidence validating plasma 3HIA-carnitine as a novel biomarker of biotin deficiency in humans. Three healthy adult subjects were successfully made marginally biotin deficient by feeding of a 30% egg-white diet for 28 days. For each subject, the plasma 3HIA-carnitine increased approximately 3-fold from Study Day 0 to Study Day 28 (p = 0.027). These results indicate that plasma 3HIA-carnitine concentration increases with biotin deficiency. If these results are confirmed in larger studies, plasma 3HIA-carnitine is likely to be an important indicator of biotin status in a variety of clinical circumstances because quantitation of 3HIA-carnitine by this method has several technical advantages over existing validated indicators of biotin status in humans.

Products