糖酵解
柠檬酸循环
厌氧糖酵解
生物
葡萄糖转运蛋白
生物能学
体内
生物化学
丙酮酸激酶
葡萄糖激酶
葡萄糖摄取
碳水化合物代谢
代谢组
线粒体
新陈代谢
化学
内分泌学
代谢物
酶
胰岛素
生物技术
作者
Huihui Li,Caroline Guglielmetti,Yoshitaka J. Sei,Misha Zilberter,Lydia M. Le Page,Lauren Shields,Joyce P. Yang,Kevin Nguyen,Brice Tiret,Gao Xiao,Neal K. Bennett,Iris Lo,Talya L. Dayton,Martin Kampmann,Yadong Huang,Jeffrey C. Rathmell,Matthew G. Vander Heiden,Myriam M. Chaumeil,Ken Nakamura
出处
期刊:Cell Reports
[Elsevier]
日期:2023-04-01
卷期号:42 (4): 112335-112335
被引量:16
标识
DOI:10.1016/j.celrep.2023.112335
摘要
Neurons require large amounts of energy, but whether they can perform glycolysis or require glycolysis to maintain energy remains unclear. Using metabolomics, we show that human neurons do metabolize glucose through glycolysis and can rely on glycolysis to supply tricarboxylic acid (TCA) cycle metabolites. To investigate the requirement for glycolysis, we generated mice with postnatal deletion of either the dominant neuronal glucose transporter (GLUT3cKO) or the neuronal-enriched pyruvate kinase isoform (PKM1cKO) in CA1 and other hippocampal neurons. GLUT3cKO and PKM1cKO mice show age-dependent learning and memory deficits. Hyperpolarized magnetic resonance spectroscopic (MRS) imaging shows that female PKM1cKO mice have increased pyruvate-to-lactate conversion, whereas female GLUT3cKO mice have decreased conversion, body weight, and brain volume. GLUT3KO neurons also have decreased cytosolic glucose and ATP at nerve terminals, with spatial genomics and metabolomics revealing compensatory changes in mitochondrial bioenergetics and galactose metabolism. Therefore, neurons metabolize glucose through glycolysis in vivo and require glycolysis for normal function.
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