REGULATION OF KETOGENESIS AND THE RENAISSANCE OF CARNITINE PALMITOYLTRANSFERASE
REGULATION OF KETOGENESIS AND THE RENAISSANCE OF CARNITINE PALMITOYLTRANSFERASE
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DOI：
10.1002/dmr.5610050305
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发表时间：
1989-05-01
期刊：
影响因子：
--
通讯作者：
FOSTER, DW
中科院分区：
文献类型：
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作者：
MCGARRY, JD;WOELTJE, KF;FOSTER, DW
普通人在长期食物匮乏的情况下生存的能力是通过一系列复杂的激素和生化信号实现的，这些信号确保了主要燃料的适当的器官间重定向和利用。在禁食的早期阶段，肝脏代谢从葡萄糖储存转变为葡萄糖产生，同时还发生其他适应，保存释放的葡萄糖以维持大脑和中枢神经系统功能。至关重要的是，体内大多数组织能够从碳水化合物转向以脂质为基础的经济，利用从脂肪库动员的脂肪酸作为其主要能量来源。肝脏的独特反应是增强其将传入的脂肪酸转化为酮体（乙酰乙酸和对羟基丁酸）的能力，酮体可作为非肝组织呼吸的辅助燃料。随着饥饿的进展，血液酮体浓度逐渐升至 5 mM 左右，使这些化合物对大脑的能量需求做出越来越大的贡献。因此减少了对肝脏糖异生的需求，从而大大节省了肌肉蛋白，这是一个明显的生存益处。生理性酮症虽然是由循环胰岛素下降引起的，但仍受到控制，因为即使面对血浆中葡萄糖的非刺激浓度（相对低血糖），I细胞仍然对游离脂肪酸和酮浓度上升的刺激有反应。在整个饥饿期间，p 细胞激素的低水平分泌可调节游离脂肪酸的释放，并防止进展为全面的酮症酸中毒。然而，这种微妙的
The ability of the average individual to survive long periods of food deprivation is made possible through a complex series of hormonal and biochemical signals that ensure the appropriate interorgan redirection and utilization of major fuels. In the early stages of a fast there is a shift of liver metabolism from glucose storage to glucose production, coupled with other adaptations that conserve the glucose released for maintenance of brain and CNS function. Crucial is the ability of most tissues in the body to switch from a carbohydrate to a lipid-based economy, utilizing fatty acids mobilized from fat depots as their main source of energy. Liver responds uniquely by enhancing its capacity to convert incoming fatty acids into ketone bodies (acetoacetic and p-hydroxybutyric acids), which serve as auxiliary fuels of respiration for nonhepatic tissues. As starvation progresses the blood ketone body concentration gradually rises to the region of 5 mM, allowing these compounds to make an increasing contribution to the energy needs of the brain. The requirement for hepatic gluconeogenesis is thus reduced, which in turn allows significant sparing of muscle protein, an event of obvious survival benefit. Physiological ketosis, although initiated by a fall in circulating insulin, is kept in check because the/I-cell remains responsive to stimulation by rising concentrations of free fatty acids and ketones even in the face of nonstimulatory concentrations of glucose in plasma (relative hypoglycemia). Low-level secretion of the p-cell hormone throughout the starvation period modulates free fatty acid release and prevents progression to full-blown ketoacidosis. However, this delicately