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

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”. How...

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Autores principales: Alfarouk, Khalid O., Ahmed, Samrein B. M., Elliott, Robert L., Benoit, Amanda, Alqahtani, Saad S., Ibrahim, Muntaser E., Bashir, Adil H. H., Alhoufie, Sari T. S., 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, Reshkin, Stephan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407102/
https://www.ncbi.nlm.nih.gov/pubmed/32664469
http://dx.doi.org/10.3390/metabo10070285
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author Alfarouk, Khalid O.
Ahmed, Samrein B. M.
Elliott, Robert L.
Benoit, Amanda
Alqahtani, Saad S.
Ibrahim, Muntaser E.
Bashir, Adil H. H.
Alhoufie, Sari T. S.
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
Reshkin, Stephan J.
author_facet Alfarouk, Khalid O.
Ahmed, Samrein B. M.
Elliott, Robert L.
Benoit, Amanda
Alqahtani, Saad S.
Ibrahim, Muntaser E.
Bashir, Adil H. H.
Alhoufie, Sari T. S.
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
Reshkin, Stephan J.
author_sort Alfarouk, Khalid O.
collection PubMed
description 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.
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spelling pubmed-74071022020-08-11 The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH Alfarouk, Khalid O. Ahmed, Samrein B. M. Elliott, Robert L. Benoit, Amanda Alqahtani, Saad S. Ibrahim, Muntaser E. Bashir, Adil H. H. Alhoufie, Sari T. S. 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 Reshkin, Stephan J. Metabolites Review 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. MDPI 2020-07-11 /pmc/articles/PMC7407102/ /pubmed/32664469 http://dx.doi.org/10.3390/metabo10070285 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Alfarouk, Khalid O.
Ahmed, Samrein B. M.
Elliott, Robert L.
Benoit, Amanda
Alqahtani, Saad S.
Ibrahim, Muntaser E.
Bashir, Adil H. H.
Alhoufie, Sari T. S.
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
Reshkin, Stephan J.
The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH
title The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH
title_full The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH
title_fullStr The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH
title_full_unstemmed The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH
title_short The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH
title_sort pentose phosphate pathway dynamics in cancer and its dependency on intracellular ph
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407102/
https://www.ncbi.nlm.nih.gov/pubmed/32664469
http://dx.doi.org/10.3390/metabo10070285
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