Aerobic Glycolysis: A DeOxymoron of (Neuro)Biology

Metabolites. 2022 Jan 13;12(1):72. doi: 10.3390/metabo12010072.

Abstract

The term 'aerobic glycolysis' has been in use ever since Warburg conducted his research on cancer cells' proliferation and discovered that cells use glycolysis to produce adenosine triphosphate (ATP) rather than the more efficient oxidative phosphorylation (oxphos) pathway, despite an abundance of oxygen. When measurements of glucose and oxygen utilization by activated neural tissue indicated that glucose was consumed without an accompanied oxygen consumption, the investigators who performed those measurements also termed their discovery 'aerobic glycolysis'. Red blood cells do not contain mitochondria and, therefore, produce their energy needs via glycolysis alone. Other processes within the central nervous system (CNS) and additional organs and tissues (heart, muscle, and so on), such as ion pumps, are also known to utilize glycolysis only for the production of ATP necessary to support their function. Unfortunately, the phenomenon of 'aerobic glycolysis' is an enigma wherever it is encountered, thus several hypotheses have been produced in attempts to explain it; that is, whether it occurs in cancer cells, in activated neural tissue, or during postprandial or exercise metabolism. Here, it is argued that, where the phenomenon in neural tissue is concerned, the prefix 'aerobic' in the term 'aerobic glycolysis' should be removed. Data collected over the past three decades indicate that L-lactate, the end product of the glycolytic pathway, plays an essential role in brain energy metabolism, justifying the elimination of the prefix 'aerobic'. Similar justification is probably appropriate for other tissues as well.

Keywords: BOLD fMRI (blood oxygen level-dependent functional magnetic resonance imaging); CMR (cerebral metabolic rate); L-lactate; aerobic glycolysis; astroglial-neuronal L-lactate shuttle; glucose; mitochondrial oxidative phosphorylation; oxygen.