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

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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.

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Abbreviations

ACC:

Acetyl-CoA carboxylase

ACO2:

Aconitase

αKG:

α-Ketoglutarate

α-KGDH :

α-Ketoglutarate dehydrogenase

ATP:

Adenosine triphosphate

CPT1:

Carnitine palmitoyltransferase 1

CiC:

Mitochondrial citrate carrier

CoA:

Acetyl coenzyme A

COX:

Cytochrome c oxidase

DC:

Dendritic cell

FADH2:

Flavin adenine dinucleotide reduced form

HIF-1α:

Inducible factor of hypoxia alpha

GSH:

Glutathione

GTP:

Guanosine triphosphate

LDH:

Lactate dehydrogenase

NADH:

Nicotinamide adenine dinucleotide

NO:

Nitric oxide

Nrf2:

NNuclear factor erythroid 2-related factor 2

ROS:

Reactive oxygen species

TCA:

Tricarboxylic acid

TCAI:

Tricarboxylic acid intermediate

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Correspondence to Geir Bjørklund.

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Gasmi, A., Peana, M., Arshad, M. et al. Krebs cycle: activators, inhibitors and their roles in the modulation of carcinogenesis. Arch Toxicol 95, 1161–1178 (2021). https://doi.org/10.1007/s00204-021-02974-9

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  • DOI: https://doi.org/10.1007/s00204-021-02974-9

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