Leung Kam
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
β-Oxidation of long-chain fatty acids is the major (60%–80%) aerobic process for energy production in the heart, liver, and skeletal muscle. Abnormalities of fatty acid oxidation (FAO) are associated with several cardiovascular diseases, neurodegeneration, fatty liver, and diabetes (1-5). Myocardium has a high mitochondrial content because of high energy usage. Carnitine palmitoyltransferases (CPT1 and CPT2) mediate transfer of fatty acids into the mitochondrial matrix for β-oxidation (6, 7). Various radiolabeled, thia-substituted, fatty acid analogs have been found to be metabolically trapped in the myocardial mitochondria (8-10). 4-Thia fatty acids are oxidized in the mitochondria to 4-thia-enoyl-CoAs, which cannot be further metabolized and trapped (protein-bound) in the mitochondria. Oleate (18:1) is preferentially oxidized relative to palmitate (16:0) and stearate (18:0) by the mitochondrial FAO (11). DeGrado et al. (12) have synthesized 18-[F]fluoro-4-thia-oleate ([F]FTO) for evaluation as a positron emission tomography (PET) agent of FAO.
长链脂肪酸的β-氧化是心脏、肝脏和骨骼肌中主要的（60% - 80%）有氧能量产生过程。脂肪酸氧化（FAO）异常与多种心血管疾病、神经退行性变、脂肪肝和糖尿病相关（1 - 5）。由于能量消耗高，心肌的线粒体含量很高。肉碱棕榈酰转移酶（CPT1和CPT2）介导脂肪酸转运至线粒体基质进行β-氧化（6, 7）。已发现各种放射性标记的、含硫取代的脂肪酸类似物在心肌线粒体中发生代谢滞留（8 - 10）。4-硫代脂肪酸在线粒体中被氧化为4-硫代烯酰辅酶A，后者无法进一步代谢并滞留（与蛋白质结合）在线粒体中。相对于棕榈酸（16:0）和硬脂酸（18:0），油酸（18:1）优先被线粒体FAO氧化（11）。DeGrado等人（12）合成了18-[F]氟-4-硫代油酸酯（[F]FTO），用于评估其作为FAO的正电子发射断层扫描（PET）剂。
