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

Authors :
Khalid O. Alfarouk
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
Stephan J. Reshkin
Source :
Metabolites, Vol 10, Iss 7, p 285 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

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.

Details

Language :
English
ISSN :
22181989
Volume :
10
Issue :
7
Database :
Directory of Open Access Journals
Journal :
Metabolites
Publication Type :
Academic Journal
Accession number :
edsdoj.97aae85c7d4744afaf11a9c2481043d5
Document Type :
article
Full Text :
https://doi.org/10.3390/metabo10070285