Cerebral metabolism of lactate in vivo:: Evidence for neuronal pyruvate carboxylation
Cerebral metabolism of lactate in vivo:: Evidence for neuronal pyruvate carboxylation
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DOI：
10.1097/00004647-200002000-00014
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发表时间：
2000-02-01
影响因子：
6.3
通讯作者：
Bråthe, A
中科院分区：
文献类型：
--
作者：
Hassel, B;Bråthe, A
观察脑内乳酸代谢。清醒的小鼠静脉注射[3-C-13]乳酸盐或[1-C-13]葡萄糖，并通过C-13核磁共振光谱分析脑和血液提取物。[3-C-13]乳酸的脑摄取和代谢是[1-C-13]葡萄糖的50%。[3-C-13]谷氨酸、γ-氨基丁酸和谷氨酰胺的C-13标记显示，乳酸几乎完全由神经元代谢，几乎不被神经胶质代谢。注射[3-C-13]乳酸盐导致大量[2-C-13]乳酸盐形成，这在[1-C-13]葡萄糖中未观察到，在先前的[2-C-13]乙酸盐研究中也未观察到。这种形成可能反映了[3-C-13]丙酮酸到苹果酸的可逆羧化和与富马酸的平衡，因为用硝基丙酸抑制琥珀酸脱氢酶并没有阻断它。在到达大脑的[3-C-13]乳酸中，20%经历了这种反应，这可能涉及神经元线粒体苹果酸酶。线粒体苹果酸酶、脱氢酶和乳酸脱氢酶的活性足以解释神经元中[2-C-13]乳酸的形成。纹状体内注射[1-C-14]丙酮酸后，谷氨酸比谷氨酰胺的比活性更高，证实了神经元丙酮酸羧化。该程序还证明了通过丙酮酸羧化形成的苹果酸与富马酸的平衡。神经元丙酮酸羧化的证明需要重新考虑神经元和神经胶质之间的代谢相互关系。
The cerebral metabolism of lactate was investigated. Awake mice received [3-C-13]lactate or [1-C-13]glucose intravenously, and brain and blood extracts were analyzed by C-13 nuclear magnetic resonance spectroscopy. The cerebral uptake and metabolism of [3-C-13]lactate was 50% that of [1-C-13]glucose. [3-C-13]Lactate was almost exclusively metabolized by neurons and hardly at all by glia, as revealed by the C-13 labeling of glutamate, gamma-aminobutyric acid and glutamine. Injection of [3-C-13]lactate led to extensive formation of [2-C-13]lactate, which was not seen with [1-C-13]glucose, nor has it been seen in previous studies with [2-C-13]acetate. This formation probably reflected reversible carboxylation of [3-C-13]pyruvate to malate and equilibration with fumarate, because inhibition of succinate dehydrogenase with nitropropionic acid did not block it. Of the [3-C-13]lactate that reached the brain, 20% underwent this reaction, which probably involved neuronal mitochondrial malic enzyme. The activities of mitochondrial malic enzyme, fumarase, and lactate dehydrogenase were high enough to account for the formation of [2-C-13]lactate in neurons. Neuronal pyruvate carboxylation was confirmed by the higher specific activity of glutamate than of glutamine after intrastriatal injection of [1-C-14]pyruvate into anesthetized mice. This procedure also demonstrated equilibration of malate, formed through pyruvate carboxylation, with fumarate. The demonstration of neuronal pyruvate carboxylation demands reconsideration of the metabolic interrelationship between neurons and glia.