Lemire Joseph, Mailloux Ryan J, Appanna Vasu D
Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada.
PLoS One. 2008 Feb 6;3(2):e1550. doi: 10.1371/journal.pone.0001550.
Lactate has long been regarded as an end product of anaerobic energy production and its fate in cerebral metabolism has not been precisely delineated. In this report, we demonstrate, for the first time, the ability of a human astrocytic cell line (CCF-STTG1) to consume lactate and to generate ATP via oxidative phosphorylation. (13)C-NMR and HPLC analyses aided in the identification of tricarboxylic acid (TCA) cyle metabolites and ATP in the astrocytic mitochondria incubated with lactate. Oxamate, an inhibitor of lactate dehydrogenase (LDH), abolished mitochondrial lactate consumption. Electrophoretic and fluorescence microscopic analyses helped localize LDH in the mitochondria. Taken together, this study implicates lactate as an important contributor to ATP metabolism in the brain, a finding that may significantly change our notion of how this important organ manipulates its energy budget.
长期以来,乳酸一直被视为无氧能量产生的终产物,其在脑代谢中的命运尚未得到精确描述。在本报告中,我们首次证明了人星形胶质细胞系(CCF-STTG1)能够消耗乳酸并通过氧化磷酸化产生ATP。(13)C-NMR和HPLC分析有助于鉴定与乳酸一起孵育的星形胶质细胞线粒体中的三羧酸(TCA)循环代谢物和ATP。乳酸脱氢酶(LDH)抑制剂草氨酸盐消除了线粒体对乳酸的消耗。电泳和荧光显微镜分析有助于将LDH定位在线粒体中。综上所述,本研究表明乳酸是大脑ATP代谢的重要贡献者,这一发现可能会显著改变我们对这个重要器官如何管理其能量预算的观念。