采用 LC-MS/MS 技术对血浆 3-羟基异戊酰肉碱进行定量检测，作为人体生物素状况的新型生物标志物。
Quantitative measurement of plasma 3-hydroxyisovaleryl carnitine by LC-MS/MS as a novel biomarker of biotin status in humans.
机构信息
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, Arkansas 72205, USA.
出版信息
Anal Chem. 2010 May 15;82(10):4140-4. doi: 10.1021/ac1003213.
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.
血浆中 3-羟基异戊酰肉碱（3HIA-肉碱）浓度升高是由于亮氨酸分解代谢途径在 3-甲基戊烯酰辅酶 A 转化为 3-甲基戊二酰辅酶 A 时受到损害所致。这种损害是由于生物素依赖性酶 3-甲基戊烯酰辅酶 A 羧化酶活性降低引起的。在这里，我们描述了一种用于定量检测血浆 3HIA-肉碱的 LC-MS/MS 方法，并初步验证了血浆 3HIA-肉碱作为人类生物素缺乏的新型生物标志物。通过 28 天喂食 30%蛋清饮食，成功使 3 名健康成年受试者处于轻度生物素缺乏状态。对于每个受试者，从研究第 0 天到第 28 天，血浆 3HIA-肉碱增加了约 3 倍（p = 0.027）。这些结果表明，血浆 3HIA-肉碱浓度随着生物素缺乏而增加。如果在更大规模的研究中得到证实，那么血浆 3HIA-肉碱很可能成为各种临床情况下生物素状态的重要指标，因为通过这种方法定量检测 3HIA-肉碱在技术上优于人类生物素状态的现有验证指标。
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