Krebs cycle: activators, inhibitors and their roles in the modulation of carcinogenesis

Arch Toxicol. 2021 Apr;95(4):1161-1178. doi: 10.1007/s00204-021-02974-9. Epub 2021 Mar 2.

Abstract

A fundamental metabolic feature of cancerous tissues is high glucose consumption. The rate of glucose consumption in a cancer cell can be 10-15 times higher than in normal cells. Isolation and cultivation of tumor cells in vitro highlight properties that are associated with intensive glucose utilization, the presence of minimal oxidative metabolism, an increase in lactate concentrations in the culture medium and a reduced rate of oxygen consumption. Although glycolysis is suggested as a general feature of malignant cells and recently identified as a possible contributing factor to tumor progression, several studies highlight distinct metabolic characteristics in some tumors, including a relative decrease in avidity compared to glucose and/or a glutamine dependency of lactate and even proliferative tumor cells. The aim of this review is to determine the particularities in the energy metabolism of cancer cells, focusing on the main nutritional substrates, such as glucose and glutamine, evaluating lactate dehydrogenase as a potential marker of malignancy and estimating activators and inhibitors in cancer treatment.

Keywords: Activators; Cancer; Glucose; Glycolysis; Inhibitors; Krebs cycle.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinogenesis / drug effects*
  • Citric Acid Cycle / drug effects*
  • Disease Progression
  • Energy Metabolism / physiology
  • Glucose / metabolism
  • Glutamine / metabolism
  • Glycolysis / physiology
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Oxygen Consumption / physiology

Substances

  • Glutamine
  • L-Lactate Dehydrogenase
  • Glucose