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The return of metabolism: biochemistry and physiology of the pentose phosphate pathway
The pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism. The PPP is important to maintain carbon homoeostasis, to provide precursors for nucleotide and amino acid biosynthesis, to provide reducing molecules for anabolism, and to defeat oxidative stress. The PPP shares r...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470864/ https://www.ncbi.nlm.nih.gov/pubmed/25243985 http://dx.doi.org/10.1111/brv.12140 |
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author | Stincone, Anna Prigione, Alessandro Cramer, Thorsten Wamelink, Mirjam M. C. Campbell, Kate Cheung, Eric Olin-Sandoval, Viridiana Grüning, Nana-Maria Krüger, Antje Alam, Mohammad Tauqeer Keller, Markus A. Breitenbach, Michael Brindle, Kevin M. Rabinowitz, Joshua D. Ralser, Markus |
author_facet | Stincone, Anna Prigione, Alessandro Cramer, Thorsten Wamelink, Mirjam M. C. Campbell, Kate Cheung, Eric Olin-Sandoval, Viridiana Grüning, Nana-Maria Krüger, Antje Alam, Mohammad Tauqeer Keller, Markus A. Breitenbach, Michael Brindle, Kevin M. Rabinowitz, Joshua D. Ralser, Markus |
author_sort | Stincone, Anna |
collection | PubMed |
description | The pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism. The PPP is important to maintain carbon homoeostasis, to provide precursors for nucleotide and amino acid biosynthesis, to provide reducing molecules for anabolism, and to defeat oxidative stress. The PPP shares reactions with the Entner–Doudoroff pathway and Calvin cycle and divides into an oxidative and non-oxidative branch. The oxidative branch is highly active in most eukaryotes and converts glucose 6-phosphate into carbon dioxide, ribulose 5-phosphate and NADPH. The latter function is critical to maintain redox balance under stress situations, when cells proliferate rapidly, in ageing, and for the ‘Warburg effect’ of cancer cells. The non-oxidative branch instead is virtually ubiquitous, and metabolizes the glycolytic intermediates fructose 6-phosphate and glyceraldehyde 3-phosphate as well as sedoheptulose sugars, yielding ribose 5-phosphate for the synthesis of nucleic acids and sugar phosphate precursors for the synthesis of amino acids. Whereas the oxidative PPP is considered unidirectional, the non-oxidative branch can supply glycolysis with intermediates derived from ribose 5-phosphate and vice versa, depending on the biochemical demand. These functions require dynamic regulation of the PPP pathway that is achieved through hierarchical interactions between transcriptome, proteome and metabolome. Consequently, the biochemistry and regulation of this pathway, while still unresolved in many cases, are archetypal for the dynamics of the metabolic network of the cell. In this comprehensive article we review seminal work that led to the discovery and description of the pathway that date back now for 80 years, and address recent results about genetic and metabolic mechanisms that regulate its activity. These biochemical principles are discussed in the context of PPP deficiencies causing metabolic disease and the role of this pathway in biotechnology, bacterial and parasite infections, neurons, stem cell potency and cancer metabolism. |
format | Online Article Text |
id | pubmed-4470864 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-44708642016-03-22 The return of metabolism: biochemistry and physiology of the pentose phosphate pathway Stincone, Anna Prigione, Alessandro Cramer, Thorsten Wamelink, Mirjam M. C. Campbell, Kate Cheung, Eric Olin-Sandoval, Viridiana Grüning, Nana-Maria Krüger, Antje Alam, Mohammad Tauqeer Keller, Markus A. Breitenbach, Michael Brindle, Kevin M. Rabinowitz, Joshua D. Ralser, Markus Biol Rev Camb Philos Soc Article The pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism. The PPP is important to maintain carbon homoeostasis, to provide precursors for nucleotide and amino acid biosynthesis, to provide reducing molecules for anabolism, and to defeat oxidative stress. The PPP shares reactions with the Entner–Doudoroff pathway and Calvin cycle and divides into an oxidative and non-oxidative branch. The oxidative branch is highly active in most eukaryotes and converts glucose 6-phosphate into carbon dioxide, ribulose 5-phosphate and NADPH. The latter function is critical to maintain redox balance under stress situations, when cells proliferate rapidly, in ageing, and for the ‘Warburg effect’ of cancer cells. The non-oxidative branch instead is virtually ubiquitous, and metabolizes the glycolytic intermediates fructose 6-phosphate and glyceraldehyde 3-phosphate as well as sedoheptulose sugars, yielding ribose 5-phosphate for the synthesis of nucleic acids and sugar phosphate precursors for the synthesis of amino acids. Whereas the oxidative PPP is considered unidirectional, the non-oxidative branch can supply glycolysis with intermediates derived from ribose 5-phosphate and vice versa, depending on the biochemical demand. These functions require dynamic regulation of the PPP pathway that is achieved through hierarchical interactions between transcriptome, proteome and metabolome. Consequently, the biochemistry and regulation of this pathway, while still unresolved in many cases, are archetypal for the dynamics of the metabolic network of the cell. In this comprehensive article we review seminal work that led to the discovery and description of the pathway that date back now for 80 years, and address recent results about genetic and metabolic mechanisms that regulate its activity. These biochemical principles are discussed in the context of PPP deficiencies causing metabolic disease and the role of this pathway in biotechnology, bacterial and parasite infections, neurons, stem cell potency and cancer metabolism. 2014-09-22 2015-08 /pmc/articles/PMC4470864/ /pubmed/25243985 http://dx.doi.org/10.1111/brv.12140 Text en http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Stincone, Anna Prigione, Alessandro Cramer, Thorsten Wamelink, Mirjam M. C. Campbell, Kate Cheung, Eric Olin-Sandoval, Viridiana Grüning, Nana-Maria Krüger, Antje Alam, Mohammad Tauqeer Keller, Markus A. Breitenbach, Michael Brindle, Kevin M. Rabinowitz, Joshua D. Ralser, Markus The return of metabolism: biochemistry and physiology of the pentose phosphate pathway |
title | The return of metabolism: biochemistry and physiology of the pentose phosphate pathway |
title_full | The return of metabolism: biochemistry and physiology of the pentose phosphate pathway |
title_fullStr | The return of metabolism: biochemistry and physiology of the pentose phosphate pathway |
title_full_unstemmed | The return of metabolism: biochemistry and physiology of the pentose phosphate pathway |
title_short | The return of metabolism: biochemistry and physiology of the pentose phosphate pathway |
title_sort | return of metabolism: biochemistry and physiology of the pentose phosphate pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470864/ https://www.ncbi.nlm.nih.gov/pubmed/25243985 http://dx.doi.org/10.1111/brv.12140 |
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