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

Khalid O Alfarouk^{1

2

3}, Samrein B M Ahmed⁴, Robert L Elliott^{5

6}, Amanda Benoit⁶, Saad S Alqahtani⁷, Muntaser E Ibrahim⁸, Adil H H Bashir⁸, Sari T S Alhoufie⁹, Gamal O Elhassan¹⁰, Christian C Wales², Laurent H Schwartz¹¹, Heyam S Ali¹², Ahmed Ahmed¹³, Patrick F Forde¹⁴, Jesus Devesa¹⁵, Rosa A Cardone¹⁶, Stefano Fais¹⁷, Salvador Harguindey¹⁸, Stephan J Reshkin¹⁶

Affiliations

¹ Alfarouk Biomedical Research LLC, Temple Terrace, FL 33617, USA.
² American Biosciences Inc., New York, NY 10913, USA.
³ Al-Ghad International College for Applied Medical Sciences, Al-Madinah Al-Munawarah 42316, Saudi Arabia.
⁴ College of Medicine, University of Sharjah, Sharjah P. O. Box 27272, UAE.
⁵ The Elliott-Elliott-Baucom Breast Cancer Research and Treatment Center, Baton Rouge, LA 70806, USA.
⁶ The Sallie A. Burdine Breast Foundation, Baton Rouge, LA 70806, USA.
⁷ Clinical Pharmacy Department, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia.
⁸ Institute of Endemic Diseases, University of Khartoum, Khartoum 11111, Sudan.
⁹ Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Al-Madinah Al-Munwarah 42353, Saudi Arabia.
¹⁰ Unaizah College of Pharmacy, Qassim University, Unaizah 56264, Saudi Arabia.
¹¹ Assistance Publique des Hôpitaux de Paris, 75003 Paris, France.
¹² Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum 11111, Sudan.
¹³ Department of Oesphogastric and General Surgery, University Hospitals of Leicester, Leicester LE5 4PW, UK.
¹⁴ CancerResearch@UCC, Western Gateway Building, University College Cork, Cork T12 XF62, Ireland.
¹⁵ Scientific Direction, Foltra Medical Centre, Travesía de Montouto 24, 15886 Teo, Spain.
¹⁶ Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, 90126 Bari, Italy.
¹⁷ Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
¹⁸ Department of Oncology, Institute for Clinical Biology and Metabolism, 01004 Vitoria, Spain.

PMID: 32664469
PMCID: PMC7407102
DOI: 10.3390/metabo10070285

Review

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

Khalid O Alfarouk et al. Metabolites. 2020.

. 2020 Jul 11;10(7):285.

doi: 10.3390/metabo10070285.

Authors

Affiliations

¹ Alfarouk Biomedical Research LLC, Temple Terrace, FL 33617, USA.
² American Biosciences Inc., New York, NY 10913, USA.
³ Al-Ghad International College for Applied Medical Sciences, Al-Madinah Al-Munawarah 42316, Saudi Arabia.
⁴ College of Medicine, University of Sharjah, Sharjah P. O. Box 27272, UAE.
⁵ The Elliott-Elliott-Baucom Breast Cancer Research and Treatment Center, Baton Rouge, LA 70806, USA.
⁶ The Sallie A. Burdine Breast Foundation, Baton Rouge, LA 70806, USA.
⁷ Clinical Pharmacy Department, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia.
⁸ Institute of Endemic Diseases, University of Khartoum, Khartoum 11111, Sudan.
⁹ Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Al-Madinah Al-Munwarah 42353, Saudi Arabia.
¹⁰ Unaizah College of Pharmacy, Qassim University, Unaizah 56264, Saudi Arabia.
¹¹ Assistance Publique des Hôpitaux de Paris, 75003 Paris, France.
¹² Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum 11111, Sudan.
¹³ Department of Oesphogastric and General Surgery, University Hospitals of Leicester, Leicester LE5 4PW, UK.
¹⁴ CancerResearch@UCC, Western Gateway Building, University College Cork, Cork T12 XF62, Ireland.
¹⁵ Scientific Direction, Foltra Medical Centre, Travesía de Montouto 24, 15886 Teo, Spain.
¹⁶ Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, 90126 Bari, Italy.
¹⁷ Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
¹⁸ Department of Oncology, Institute for Clinical Biology and Metabolism, 01004 Vitoria, Spain.

PMID: 32664469
PMCID: PMC7407102
DOI: 10.3390/metabo10070285

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.

Keywords: cancer; enzyme; metabolism; pH; redox.

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Conflict of interest statement

Author K.O.A. and C.W. are employed by the American Biosciences Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

**Figure 1**
Scheme showing the interaction between glycolysis and PPP.

**Figure 2**
Glutathione Reductase Cycle.

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

LinkOut - more resources

Full Text Sources

Other Literature Sources