Yudkoff Marc, Daikhin Yevgeny, Nissim Ilana, Lazarow Adam, Nissim Itzhak
Department of Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA.
Prostaglandins Leukot Essent Fatty Acids. 2004 Mar;70(3):277-85. doi: 10.1016/j.plefa.2003.07.005.
We do not know the mode of action of the ketogenic diet in controlling epilepsy. One possibility is that the diet alters brain handling of glutamate, the major excitatory neurotransmitter and a probable factor in evoking and perpetuating a convulsion. We have found that brain metabolism of ketone bodies can furnish as much as 30% of glutamate and glutamine carbon. Ketone body metabolism also provides acetyl-CoA to the citrate synthetase reaction, in the process consuming oxaloacetate and thereby diminishing the transamination of glutamate to aspartate, a pathway in which oxaloacetate is a reactant. Relatively more glutamate then is available to the glutamate decarboxylase reaction, which increases brain [GABA]. Ketosis also increases brain [GABA] by increasing brain metabolism of acetate, which glia convert to glutamine. GABA-ergic neurons readily take up the latter amino acid and use it as a precursor to GABA. Ketosis also may be associated with altered amino acid transport at the blood-brain barrier. Specifically, ketosis may favor the release from brain of glutamine, which transporters at the blood-brain barrier exchange for blood leucine. Since brain glutamine is formed in astrocytes from glutamate, the overall effect will be to favor the release of glutamate from the nervous system.
我们尚不清楚生酮饮食控制癫痫的作用机制。一种可能性是，该饮食改变了大脑对谷氨酸的处理方式，谷氨酸是主要的兴奋性神经递质，也是引发和持续惊厥的一个可能因素。我们发现，酮体的脑代谢能够提供高达30%的谷氨酸和谷氨酰胺碳源。酮体代谢还为柠檬酸合酶反应提供乙酰辅酶A，在此过程中消耗草酰乙酸，从而减少谷氨酸向天冬氨酸的转氨基作用，而草酰乙酸是该转氨基途径中的一种反应物。这样一来，相对更多的谷氨酸可用于谷氨酸脱羧酶反应，进而增加脑内γ-氨基丁酸（GABA）含量。酮症还通过增加乙酸的脑代谢来提高脑内GABA含量，乙酸可被神经胶质细胞转化为谷氨酰胺。GABA能神经元很容易摄取后一种氨基酸并将其用作GABA的前体。酮症还可能与血脑屏障处氨基酸转运的改变有关。具体而言，酮症可能有利于脑内谷氨酰胺的释放，血脑屏障处的转运体可将谷氨酰胺与血液中的亮氨酸进行交换。由于脑内谷氨酰胺是由星形胶质细胞中的谷氨酸形成的，总体效果将是有利于谷氨酸从神经系统释放。
