title: Quantitative measurement of plasma 3-hydroxyisovaleryl carnitine by LC-MS/MS as a novel biomarker of biotin status in humans.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, Arkansas 72205, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Horvath
authors.forename: Shawna L
authors.initials: SL
authors.lastname: Stratton
authors.forename: Anna
authors.initials: A
authors.lastname: Bogusiewicz
authors.forename: Lindsay
authors.initials: L
authors.lastname: Pack
authors.forename: Jeffery
authors.initials: J
authors.lastname: Moran
authors.forename: Donald M
authors.initials: DM
authors.lastname: Mock
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001710:Biotin / Q000737:chemistry*; D001774:Blood Chemical Analysis; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D014803:Vitamin B Complex / Q000097:blood*
chemical_list: C098116:3-hydroxyisovalerylcarnitine; D015415:Biomarkers; D014803:Vitamin B Complex; D001710:Biotin; D002331:Carnitine
references.citation: J Lipid Res. 1997 Jan;38(1):173-82
references.pmid: 9034211
references.citation: J Nutr. 2009 Jan;139(1):154-7
references.pmid: 19056637
references.citation: Proc Soc Exp Biol Med. 2000 Jan;223(1):14-21
references.pmid: 10632957
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jul 15;870(2):154-9
references.pmid: 18088573
references.citation: Teratology. 1990 Sep;42(3):295-300
references.pmid: 2274895
references.citation: J Nutr. 2005 Jan;135(1):42-7
references.pmid: 15623830
references.citation: J Nutr. 2005 May;135(5):973-7
references.pmid: 15867267
references.citation: Pediatrics. 2006 Dec;118(6):2555-6
references.pmid: 17142544
references.citation: J Nutr. 2002 Jul;132(7):1945-50
references.pmid: 12097674
references.citation: Am J Clin Nutr. 2006 Aug;84(2):384-8
references.pmid: 16895887
references.citation: J Nutr. 1992 Jul;122(7):1493-9
references.pmid: 1619476
references.citation: Am J Clin Nutr. 2002 Feb;75(2):295-9
references.pmid: 11815321
references.citation: Clin Chim Acta. 1995 Aug 31;240(1):35-51
references.pmid: 8582058
references.citation: Int J Biochem Cell Biol. 1998 Jan;30(1):1-5
references.pmid: 9597748
references.citation: Mol Genet Metab. 2008 Dec;95(4):201-5
references.pmid: 18974016
references.citation: J Nutr Biochem. 1999 Mar;10(3):128-38
references.pmid: 15539280
references.citation: Am J Hum Genet. 1982 Sep;34(5):699-716
references.pmid: 6127031
references.citation: J Inherit Metab Dis. 1994;17(6):678-90
references.pmid: 7707691
references.citation: J Nutr. 1991 Jan;121(1):101-4
references.pmid: 1992046