Rethinking the Citric Acid Cycle: Connecting Pyruvate Carboxylase and Citrate Synthase to the Flow of Energy and Material

Int J Mol Sci. 2021 Jan 9;22(2):604. doi: 10.3390/ijms22020604.

Abstract

In 1937, Sir H. A Krebs first published the Citric Acid Cycle, a unidirectional cycle with carboxylic acids. The original concept of the Citric Acid Cycle from Krebs' 1953 Nobel Prize lecture illustrates the unidirectional degradation of lactic acid to water, carbon dioxide and hydrogen. Here, we add the heart lactate dehydrogenase•proton-linked monocarboxylate transporter 1 complex, connecting the original Citric Acid Cycle to the flow of energy and material. The heart lactate dehydrogenase•proton-linked monocarboxylate transporter 1 complex catalyses the first reaction of the Citric Acid Cycle, the oxidation of lactate to pyruvate, and thus secures the provision of pyruvic acid. In addition, we modify Krebs' original concept by feeding the cycle with oxaloacetic acid. Our concept enables the integration of anabolic processes and allows adaption of the organism to recover ATP faster.

Keywords: Citric Acid Cycle; exercise; malic acid; memory formation; oxidative phosphorylation; succinic acid.

Publication types

  • Review

MeSH terms

  • Animals
  • Citrate (si)-Synthase / metabolism*
  • Citric Acid Cycle*
  • Exercise
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Monocarboxylic Acid Transporters / metabolism
  • Oxidative Phosphorylation
  • Protons
  • Pyruvate Carboxylase / metabolism*
  • Symporters / metabolism

Substances

  • Monocarboxylic Acid Transporters
  • Protons
  • Symporters
  • monocarboxylate transport protein 1
  • L-Lactate Dehydrogenase
  • Citrate (si)-Synthase
  • Pyruvate Carboxylase