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人类大脑通过三羧酸循环利用乳酸:13C 标记微透析和高分辨率核磁共振研究。

The human brain utilizes lactate via the tricarboxylic acid cycle: a 13C-labelled microdialysis and high-resolution nuclear magnetic resonance study.

机构信息

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, UK.

出版信息

Brain. 2009 Oct;132(Pt 10):2839-49. doi: 10.1093/brain/awp202. Epub 2009 Aug 20.

DOI:10.1093/brain/awp202
PMID:19700417
Abstract

Energy metabolism in the human brain is not fully understood. Classically, glucose is regarded as the major energy substrate. However, lactate (conventionally a product of anaerobic metabolism) has been proposed to act as an energy source, yet whether this occurs in man is not known. Here we show that the human brain can indeed utilize lactate as an energy source via the tricarboxylic acid cycle. We used a novel combination of (13)C-labelled cerebral microdialysis both to deliver (13)C substrates into the brain and recover (13)C metabolites from the brain, and high-resolution (13)C nuclear magnetic resonance. Microdialysis catheters were placed in the vicinity of focal lesions and in relatively less injured regions of brain, in patients with traumatic brain injury. Infusion with 2-(13)C-acetate or 3-(13)C-lactate produced (13)C signals for glutamine C4, C3 and C2, indicating tricarboxylic acid cycle operation followed by conversion of glutamate to glutamine. This is the first direct demonstration of brain utilization of lactate as an energy source in humans.

摘要

人类大脑的能量代谢尚未被完全理解。传统上,葡萄糖被认为是主要的能量底物。然而,乳酸(通常是无氧代谢的产物)已被提议作为能量来源,但在人类中是否发生这种情况尚不清楚。在这里,我们表明人脑确实可以通过三羧酸循环利用乳酸作为能量来源。我们使用了一种新型的(13)C 标记脑微透析技术,将(13)C 底物输送到大脑中,并从大脑中回收(13)C 代谢物,同时使用高分辨率(13)C 核磁共振。微透析导管放置在创伤性脑损伤患者的局灶性病变附近和相对损伤较轻的脑区。输注 2-(13)C-乙酸盐或 3-(13)C-乳酸会产生谷氨酰胺 C4、C3 和 C2 的(13)C 信号,表明三羧酸循环运行后,谷氨酸转化为谷氨酰胺。这是首次直接证明人类大脑利用乳酸作为能量来源。

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