Morris A A M
Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Hospital Road, Pendlebury, Manchester, M27 4HA, UK.
J Inherit Metab Dis. 2005;28(2):109-21. doi: 10.1007/s10545-005-5518-0.
Ketone bodies (KBs) are an important source of energy for the brain. During the neonatal period, they are also precursors for the synthesis of lipids (especially cholesterol) and amino acids. The rate of cerebral KB metabolism depends primarily on the concentration in blood; high concentrations occur during fasting and on a high-fat diet. Cerebral KB metabolism is also regulated by the permeability of the blood-brain barrier (BBB), which depends on the abundance of monocarboxylic acid transporters (MCT1). The BBB's permeability to KBs increases with fasting in humans. In rats, permeability increases during the suckling period, but human neonates have not been studied. Monocarboxylic acid transporters are also present in the plasma membranes of neurons and glia but their role in regulating KB metabolism is uncertain. Finally, the rate of cerebral KB metabolism depends on the activities of the relevant enzymes in brain. The activities vary with age in rats, but reliable results are not available for humans. Cerebral KB metabolism in humans differs from that in the rat in several respects. During fasting, for example, KBs supply more of the brain's energy in humans than in the rat. Conversely, KBs are probably used more extensively in the brain of suckling rats than in human neonates. These differences complicate the interpretation of rodent studies. Most patients with inborn errors of ketogenesis develop normally, suggesting that the only essential role for KBs is as an alternative fuel during illness or prolonged fasting. On the other hand, in HMG-CoA lyase deficiency, imaging generally shows asymptomatic white-matter abnormalities. The ability of KBs to act as an alternative fuel explains the effectiveness of the ketogenic diet in GLUT1 deficiency, but its effectiveness in epilepsy remains unexplained.
酮体（KBs）是大脑重要的能量来源。在新生儿期，它们也是脂质（尤其是胆固醇）和氨基酸合成的前体。脑酮体代谢速率主要取决于血液中的浓度；禁食和高脂饮食期间浓度会升高。脑酮体代谢还受血脑屏障（BBB）通透性的调节，而血脑屏障的通透性取决于单羧酸转运体（MCT1）的丰度。人类禁食时血脑屏障对酮体的通透性会增加。在大鼠中，哺乳期血脑屏障的通透性会增加，但尚未对人类新生儿进行研究。单羧酸转运体也存在于神经元和神经胶质细胞的质膜中，但其在调节酮体代谢中的作用尚不确定。最后，脑酮体代谢速率取决于脑中相关酶的活性。在大鼠中，这些酶的活性随年龄变化，但尚无关于人类的可靠研究结果。人类的脑酮体代谢在几个方面与大鼠不同。例如，禁食期间，酮体为人类大脑提供的能量比大鼠更多。相反，哺乳期大鼠大脑中酮体的使用可能比人类新生儿更为广泛。这些差异使得对啮齿动物研究结果的解读变得复杂。大多数患有先天性酮生成障碍的患者发育正常，这表明酮体唯一的重要作用是在患病或长期禁食期间作为替代燃料。另一方面，在HMG - CoA裂解酶缺乏症中，影像学检查通常显示无症状的白质异常。酮体作为替代燃料的能力解释了生酮饮食对GLUT1缺乏症的有效性，但其对癫痫的有效性仍无法解释。
