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