The acylcarnitines comprise a wide range of acyl groups linked via an ester bond to the hydroxyl group of L-carnitine. Mass spectrometry methods are capable of measuring the relative abundance of hundreds of acylcarnitines in a single drop of blood. As such, acylcarnitines can serve as sensitive biomarkers of disease. For certain acylcarnitines, however, their biochemical origin, and biomedical significance, remain unclear. One such example is 3-methylglutaryl (3MG) carnitine (C5-3M-DC). Whereas 3MG carnitine levels are normally very low, elevated levels are detected in discrete inborn errors of metabolism (IEM) as well as different forms of heart disease. Moreover, acute injury, including γ radiation exposure, paraquat poisoning, and traumatic brain injury manifest elevated levels of 3MG carnitine in blood and/or urine. Recent evidence indicates that two distinct biosynthetic routes to 3MG carnitine exist. The first, caused by an inherited deficiency in the leucine catabolism pathway enzyme, 3-hydroxy-3-methylglutaryl (HMG) CoA lyase, leads to a buildup of -3-methylglutaconyl (3MGC) CoA. Reduction of the double bond in -3MGC CoA generates 3MG CoA, which is then converted to 3MG carnitine by carnitine acyltransferase. This route, however, cannot explain why 3MG carnitine levels increase in IEMs that do not affect leucine metabolism or various chronic and acute disease states. In these cases, disease-related defects in aerobic energy metabolism result in diversion of acetyl CoA to -3MGC CoA. Once formed, -3MGC CoA is reduced to 3MG CoA and esterified to form 3MG carnitine. Thus, 3MG carnitine, represents a potential biomarker of disease processes associated with compromised mitochondrial energy metabolism.

中文翻译：

---

3-甲基戊二酰肉碱：线粒体功能障碍的生物标志物


酰基肉碱包含多种酰基，这些酰基通过酯键与 L-肉碱的羟基相连。质谱法能够测量一滴血液中数百种酰基肉碱的相对丰度。因此，酰基肉碱可以作为疾病的敏感生物标志物。然而，对于某些酰基肉碱，它们的生化来源和生物医学意义仍不清楚。一个这样的例子是 3-甲基戊二酰 （3MG） 肉碱 （C5-3M-DC）。虽然 3MG 肉碱水平通常非常低，但在离散的先天性代谢缺陷 （IEM） 以及不同形式的心脏病中检测到水平升高。此外，急性损伤，包括γ辐射暴露、百草枯中毒和创伤性脑损伤，血液和/或尿液中 3 毫克肉碱水平升高。最近的证据表明，存在两种不同的 3MG 肉碱生物合成途径。第一种是由亮氨酸分解代谢途径酶 3-羟基-3-甲基戊二酰 （HMG） 辅酶 A 裂解酶的遗传性缺陷引起的，导致 -3-甲基戊二酰 （3MGC） 辅酶 A 的积累。-3MGC CoA 中双键的还原产生 3MG CoA，然后通过肉碱酰基转移酶转化为 3MG 肉碱。然而，这条途径无法解释为什么 3MG 肉碱水平在 IEM 中增加，而不会影响亮氨酸代谢或各种慢性和急性疾病状态。在这些情况下，有氧能量代谢中与疾病相关的缺陷导致乙酰辅酶 A 转移到 -3MGC 辅酶 A。一旦形成，-3MGC CoA 被还原为 3MG CoA 并酯化形成 3MG 肉碱。因此，3MG 肉碱代表了与线粒体能量代谢受损相关的疾病过程的潜在生物标志物。