The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH

ALFAROUK, Khalid O, AHMED, Samrein, ELLIOTT, Robert L, BENOIT, Amanda, ALQAHTANI, Saad S, IBRAHIM, Muntaser E, BASHIR, Adil HH, ALHOUFIE, Sari TS, ELHASSAN, Gamal O, WALES, Christian C, SCHWARTZ, Laurent H, ALI, Heyam S, AHMED, Ahmed, FORDE, Patrick F, DEVESA, Jesus, CARDONE, Rosa A, FAIS, Stefano, HARGUINDEY, Salvador and RESHKIN, Stephan J (2020). The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH. Metabolites, 10 (7): 285.

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Abstract

The Pentose Phosphate Pathway (PPP) is one of the key metabolic pathways occurring in living cells to produce energy and maintain cellular homeostasis. Cancer cells have higher cytoplasmic utilization of glucose (glycolysis), even in the presence of oxygen; this is known as the “Warburg Effect”. However, cytoplasmic glucose utilization can also occur in cancer through the PPP. This pathway contributes to cancer cells by operating in many different ways: (i) as a defense mechanism via the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) to prevent apoptosis, (ii) as a provision for the maintenance of energy by intermediate glycolysis, (iii) by increasing genomic material to the cellular pool of nucleic acid bases, (iv) by promoting survival through increasing glycolysis, and so increasing acid production, and (v) by inducing cellular proliferation by the synthesis of nucleic acid, fatty acid, and amino acid. Each step of the PPP can be upregulated in some types of cancer but not in others. An interesting aspect of this metabolic pathway is the shared regulation of the glycolytic and PPP pathways by intracellular pH (pHi). Indeed, as with glycolysis, the optimum activity of the enzymes driving the PPP occurs at an alkaline pHi, which is compatible with the cytoplasmic pH of cancer cells. Here, we outline each step of the PPP and discuss its possible correlation with cancer.

Item Type:	Article
Uncontrolled Keywords:	0301 Analytical Chemistry; 0601 Biochemistry and Cell Biology; 1103 Clinical Sciences; 3101 Biochemistry and cell biology; 3205 Medical biochemistry and metabolomics; 3401 Analytical chemistry
Identification Number:	https://doi.org/10.3390/metabo10070285
SWORD Depositor:	Symplectic Elements
Depositing User:	Symplectic Elements
Date Deposited:	25 Jan 2024 16:44
Last Modified:	19 Apr 2024 08:00
URI:	https://shura.shu.ac.uk/id/eprint/33082

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