Yudkoff M, Daikhin Y, Nissim I, Lazarow A, Nissim I
Division of Child Development and Rehabilitation, Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA.
J Neurosci Res. 2001 Oct 15;66(2):272-81. doi: 10.1002/jnr.1221.
The relationship between ketosis and brain amino acid metabolism was studied in mice that consumed a ketogenic diet (>90% of calories as lipid). After 3 days on the diet the blood concentration of 3-OH-butyrate was approximately 5 mmol/l (control = 0.06-0.1 mmol/l). In forebrain and cerebellum the concentration of 3-OH-butyrate was approximately 10-fold higher than control. Brain [citrate] and [lactate] were greater in the ketotic animals. The concentration of whole brain free coenzyme A was lower in ketotic mice. Brain [aspartate] was reduced in forebrain and cerebellum, but [glutamate] and [glutamine] were unchanged. When [(15)N]leucine was administered to follow N metabolism, this labeled amino acid accumulated to a greater extent in the blood and brain of ketotic mice. Total brain aspartate ((14)N + (15)N) was reduced in the ketotic group. The [(15)N]aspartate/[(15)N]glutamate ratio was lower in ketotic animals, consistent with a shift in the equilibrium of the aspartate aminotransferase reaction away from aspartate. Label in [(15)N]GABA and total [(15)N]GABA was increased in ketotic animals. When the ketotic animals were injected with glucose, there was a partial blunting of ketoacidemia within 40 min as well as an increase of brain [aspartate], which was similar to control. When [U-(13)C(6)]glucose was injected, the (13)C label appeared rapidly in brain lactate and in amino acids. Label in brain [U-(13)C(3)]lactate was greater in the ketotic group. The ratio of brain (13)C-amino acid/(13)C-lactate, which reflects the fraction of amino acid carbon that is derived from glucose, was much lower in ketosis, indicating that another carbon source, i.e., ketone bodies, were precursor to aspartate, glutamate, glutamine and GABA.
在食用生酮饮食（>90%的热量来自脂质）的小鼠中研究了酮症与脑氨基酸代谢之间的关系。饮食3天后，3-羟基丁酸的血浓度约为5 mmol/l（对照组 = 0.06 - 0.1 mmol/l）。在前脑和小脑中，3-羟基丁酸的浓度比对照组高约10倍。生酮动物的脑[柠檬酸]和[乳酸]更高。生酮小鼠全脑游离辅酶A的浓度较低。前脑和小脑中脑[天冬氨酸]降低，但[谷氨酸]和[谷氨酰胺]未改变。当给予[(15)N]亮氨酸以追踪氮代谢时，这种标记氨基酸在生酮小鼠的血液和脑中积累的程度更大。生酮组全脑天冬氨酸（(14)N + (15)N）降低。生酮动物中[(15)N]天冬氨酸/[(15)N]谷氨酸的比值较低，这与天冬氨酸转氨酶反应平衡远离天冬氨酸的转变一致。生酮动物中[(15)N]γ-氨基丁酸的标记和总[(15)N]γ-氨基丁酸增加。当给生酮动物注射葡萄糖时，40分钟内酮血症部分减轻，脑[天冬氨酸]增加，与对照组相似。当注射[U-(13)C(6)]葡萄糖时，(13)C标记迅速出现在脑乳酸和氨基酸中。生酮组脑[U-(13)C(3)]乳酸中的标记更大。反映来自葡萄糖的氨基酸碳分数的脑(13)C-氨基酸/(13)C-乳酸的比值在酮症时低得多，表明另一种碳源，即酮体，是天冬氨酸、谷氨酸、谷氨酰胺和γ-氨基丁酸的前体。
