期刊
ANALYTICAL CHEMISTRY
卷 82, 期 10, 页码 4140-4144出版社
AMER CHEMICAL SOC
DOI: 10.1021/ac1003213
关键词
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资金
- National Institutes of Health [R37 DK36823, R37 DK36823-26S1, R01 DK79890-01S1]
- Centers for Disease Control [200-2007-21729]
- Bioterrorism Cooperative Agreement [U90/CCU616974-07]
- Association of Public Health Laboratories
- National Center For Research Resources [1UL1RR029884]
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.
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