Hassel B, Bråthe A
Division for Environmental Toxicology, Norwegian Defense Research Establishment, Kjeller, Norway.
J Cereb Blood Flow Metab. 2000 Feb;20(2):327-36. doi: 10.1097/00004647-200002000-00014.
The cerebral metabolism of lactate was investigated. Awake mice received [3-13C]lactate or [1-13C]glucose intravenously, and brain and blood extracts were analyzed by 13C nuclear magnetic resonance spectroscopy. The cerebral uptake and metabolism of [3-13C]lactate was 50% that of [1-13C]glucose. [3-13C]Lactate was almost exclusively metabolized by neurons and hardly at all by glia, as revealed by the 13C labeling of glutamate, gamma-aminobutyric acid and glutamine. Injection of [3-13C]lactate led to extensive formation of [2-13C]lactate, which was not seen with [1-13C]glucose, nor has it been seen in previous studies with [2-13C]acetate. This formation probably reflected reversible carboxylation of [3-13C]pyruvate to malate and equilibration with fumarate, because inhibition of succinate dehydrogenase with nitropropionic acid did not block it. Of the [3-13C]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 [2-13C]lactate in neurons. Neuronal pyruvate carboxylation was confirmed by the higher specific activity of glutamate than of glutamine after intrastriatal injection of [1-14C]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.
对乳酸的脑代谢进行了研究。清醒小鼠静脉注射[3-¹³C]乳酸或[1-¹³C]葡萄糖，然后通过¹³C核磁共振波谱分析脑和血提取物。[3-¹³C]乳酸的脑摄取和代谢是[1-¹³C]葡萄糖的50%。如谷氨酸、γ-氨基丁酸和谷氨酰胺的¹³C标记所示，[3-¹³C]乳酸几乎完全由神经元代谢，而几乎不由神经胶质细胞代谢。注射[3-¹³C]乳酸导致大量[2-¹³C]乳酸形成，这在注射[1-¹³C]葡萄糖时未见到，在之前用[2-¹³C]乙酸的研究中也未见到。这种形成可能反映了[3-¹³C]丙酮酸可逆羧化生成苹果酸并与富马酸达到平衡，因为用硝基丙酸抑制琥珀酸脱氢酶并不能阻止它。到达脑的[3-¹³C]乳酸中，20%发生了这种反应，这可能涉及神经元线粒体苹果酸酶。线粒体苹果酸酶、延胡索酸酶和乳酸脱氢酶的活性高到足以解释神经元中[2-¹³C]乳酸的形成。在麻醉小鼠纹状体内注射[1-¹⁴C]丙酮酸后，谷氨酸的比活性高于谷氨酰胺，从而证实了神经元丙酮酸羧化作用。该过程还证明了通过丙酮酸羧化形成的苹果酸与富马酸达到平衡。神经元丙酮酸羧化作用的证明需要重新考虑神经元与神经胶质细胞之间的代谢相互关系。
