Lactate: the ultimate cerebral oxidative energy substrate?

• Published in: Journal of cerebral blood flow and metabolism 2006-01, Vol.26 (1), p.142-152
• Main Author: Schurr, Avital
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain - metabolism; Brain - physiology; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Energy Metabolism - physiology; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Glycolysis; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Lactic Acid - metabolism; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/sj.jcbfm.9600174

Research over the past two decades has renewed the interest in lactate, no longer as a useless end product of anaerobic glycolysis in brain (and other tissues), but as an oxidative substrate for energy metabolism. While this topic would be considered blasphemy only three decades ago, much recent evidence indicates that lactate does play a major role in aerobic energy metabolism in the brain, the heart, skeletal muscle, and possibly in any other tissue and organ. Nevertheless, this concept has challenged the old dogma and ignited a fierce debate, especially among neuroscientists, pitting the supporters of glucose as the major oxidative energy substrate against those who support lactate as a possible alternative to glucose under certain conditions. Meanwhile, researchers working on energy metabolism in skeletal muscle have taken great strides toward bridging between these two extreme positions, while avoiding the high decibels of an emotional debate. Employing their findings along with the existing old and new data on cerebral energy metabolism, it is postulated here that lactate is the only major product of cerebral (and other tissues) glycolysis, whether aerobic or anaerobic, neuronal or astrocytic, under rest or during activation. Consequently, this postulate entails that lactate is a major, if not the only, substrate for the mitochondrial tricarboxylic acid cycle. If proven true, this hypothesis could provide better understanding of the biochemistry and physiology of (cerebral) energy metabolism, while holding important implications in the field of neuroimaging. Concomitantly, it could satisfy both ‘glucoseniks’ and ‘lactatians’ in the ongoing debate.