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Metabolites
Volume 10
Issue 7
10.3390/metabo10070285
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The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH

by
Khalid O. Alfarouk
1,2,3,*,
Samrein B. M. Ahmed
4,
Robert L. Elliott
5,6,
Amanda Benoit
6,
Saad S. Alqahtani
7,
Muntaser E. Ibrahim
8,
Adil H. H. Bashir
8,
Sari T. S. Alhoufie
9,
Gamal O. Elhassan
10,
Christian C. Wales
2,
Laurent H. Schwartz
11,
Heyam S. Ali
12,
Ahmed Ahmed
13,
Patrick F. Forde
14,
Jesus Devesa
15,
Rosa A. Cardone
16,
Stefano Fais
17,
Salvador Harguindey
18 and
Stephan J. Reshkin
16
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
[email protected], 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
 
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Metabolites 2020, 10(7), 285; https://doi.org/10.3390/metabo10070285
Received: 21 May 2020 / Revised: 2 July 2020 / Accepted: 6 July 2020 / Published: 11 July 2020
(This article belongs to the Section Cell Metabolism)
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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. View Full-Text
Keywords: cancer; metabolism; enzyme; pH; redox cancer; metabolism; enzyme; pH; redox
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MDPI and ACS Style

Alfarouk, K.O.; Ahmed, S.B.M.; Elliott, R.L.; Benoit, A.; Alqahtani, S.S.; Ibrahim, M.E.; Bashir, A.H.H.; Alhoufie, S.T.S.; Elhassan, G.O.; Wales, C.C.; Schwartz, L.H.; Ali, H.S.; Ahmed, A.; Forde, P.F.; Devesa, J.; Cardone, R.A.; Fais, S.; Harguindey, S.; Reshkin, S.J. The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH. Metabolites 2020, 10, 285. https://doi.org/10.3390/metabo10070285

AMA Style

Alfarouk KO, Ahmed SBM, Elliott RL, Benoit A, Alqahtani SS, Ibrahim ME, Bashir AHH, Alhoufie STS, Elhassan GO, Wales CC, Schwartz LH, Ali HS, Ahmed A, Forde PF, Devesa J, Cardone RA, Fais S, Harguindey S, Reshkin SJ. The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH. Metabolites. 2020; 10(7):285. https://doi.org/10.3390/metabo10070285

Chicago/Turabian Style

Alfarouk, Khalid O., Samrein B.M. Ahmed, Robert L. Elliott, Amanda Benoit, Saad S. Alqahtani, Muntaser E. Ibrahim, Adil H.H. Bashir, Sari T.S. Alhoufie, Gamal O. Elhassan, Christian C. Wales, Laurent H. Schwartz, Heyam S. Ali, Ahmed Ahmed, Patrick F. Forde, Jesus Devesa, Rosa A. Cardone, Stefano Fais, Salvador Harguindey, and Stephan J. Reshkin. 2020. "The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH" Metabolites 10, no. 7: 285. https://doi.org/10.3390/metabo10070285

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