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

Authors :
Stephan J. Reshkin
Ahmed Qasim Ahmed
Samrein B M Ahmed
Christian C. Wales
Robert L. Elliott
Sari T S Alhoufie
Adil H. H. Bashir
Laurent Schwartz
Jesús Devesa
Muntaser E. Ibrahim
Heyam Saad Ali
Salvador Harguindey
Gamal O. Elhassan
Khalid O. Alfarouk
Patrick F. Forde
Saad S. Alqahtani
Stefano Fais
Rosa Angela Cardone
Amanda Benoit
Source :
Metabolites, Vol 10, Iss 285, p 285 (2020), Metabolites
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

ISSN :
22181989
Volume :
10
Database :
OpenAIRE
Journal :
Metabolites
Accession number :
edsair.doi.dedup.....c2bb4088bb1abb7af85616f493aca7e0
Full Text :
https://doi.org/10.3390/metabo10070285