Pentose phosphate pathway in senescent cells (Homo sapiens)

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2-51Lower levels of the NADP+/NADPH ratioupregulate the regenartion of NADPH.D-Erythrose-4-phosphateRibulose-phosphate 3-epimeraseD-Ribose-5-phosphateD-glyceraldehyde-3-phosphateacetaldehyde5-phospho-D-ribose-1-pyrophosphoric acidD-ribose-1-phosphateD-glyceraldehyde-3-phosphateD-Xylulose-5-phosphateH+TransketolaseD-Fructose-6-PhosphateOncogene Induced SenescenceD-glucono-1,5-lactone-6-phosphateRibose phophate isomeraseOncogene Induced SenescenceRibose-phosphate pyrophosphokinaseTP53ATP6-phosphogluconolactonaseTransketolaseDeoxyribose-phophate aldolasePurine metabolismAMPD-Ribulose-5-phosphatePhosphoglucomutaseNADP+G6PD6-Phospho-D-gluconatePE-Induced SenescenceH+D-Glucose-6-Phosphate[CO2]Pyrimidine metabolism6-phosphogluconolactonate dehydrogenaseGlycolysisD-Fructose-6-PhosphateNADPHD-sedoheptulose-7-phosphateNADP+2-deoxy-D-ribose-5-phosphateTransaldolaseNADPHNADP+NADPH


The pentose phosphate pathway is an important route for glucose oxidation. This pathway is divided over 2 different branches; the non-oxidative and the oxidative. The oxidative branch supports the regeneration of reduced NADPH, while converting glucose-6-phosphate into ribulose-5-phosphate and CO2 in an unidirectional way. This branch is also linked to glycolysis at the glucose-6-phosphate level, while the non-oxidative branch is linked to glycolysis in a bidirectional way, depending on the availability of the intermediates glyceraldehyde-3-phosphate and fructose-6-phosphate. This non-oxidative branch converts pentose phosphates into phosphorylated ketones and aldoses (Almeida et al., 2018). During this process, ribose-5-phosphate is produced, which is an important precursor for nucleotide synthesis. The regeneration of the NADPH by the oxidative branch, is regulated by the NADP+/NADPH ratio. When this ratio is lower, due to lower levels of NADPH, the regeneration of NADPH is stimulated in order to maintain the balance (Clement et al., 2019). In case of senescence, OIS heightens this ratio, while proliferative exhaustion-induced senescence lowers this ratio. Furthermore, p53 lowers glycolysis by lowering the level of fructose-2,6-bisphosphate. The PPP is also upregulated due to oxidative stress and by conditions of low stress induced by P53, which is symptomatic of PE-induced senescence (Zhang et al., 2016). Another study by Wu et al. (2017) showed that one of the rate-limiting enzymes, 6-phosphogluconate dehydrogenase (6PGDH), is upregulated in OIS, due to which the PPP is also upregulated again.

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  1. Wu M, Ye H, Shao C, Zheng X, Li Q, Wang L, Zhao M, Lu G, Chen B, Zhang J, Wang Y, Wang G, Hao H; ''Metabolomics-Proteomics Combined Approach Identifies Differential Metabolism-Associated Molecular Events between Senescence and Apoptosis.''; J Proteome Res, 2017 PubMed Europe PMC Scholia
  2. Zhang ZZ, Lee EE, Sudderth J, Yue Y, Zia A, Glass D, Deberardinis RJ, Wang RC; ''Glutathione Depletion, Pentose Phosphate Pathway Activation, and Hemolysis in Erythrocytes Protecting Cancer Cells from Vitamin C-induced Oxidative Stress.''; J Biol Chem, 2016 PubMed Europe PMC Scholia
  3. Birgit Veldman; ''Metabolic hallmarks of cellular senescence: highlighting the role of intracellular pathways in various senescent phenotypes''; , 2020
  4. Ana S. Almeide, Nuno L. Soares, Catarina O. Sequeira, Sofia A. Pereira, Ursula Sonnewald, Helena L.A. Vieira; ''Improvement of neuronal differentiation by carbon monoxide: Role of pentose phosphate pathway''; Elsevier, 2018
  5. Clement J, Wong M, Poljak A, Sachdev P, Braidy N; ''The Plasma NAD+Metabolome Is Dysregulated in "Normal" Aging.''; Rejuvenation Res, 2019 PubMed Europe PMC Scholia


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120456view05:57, 4 December 2021EgonwRemoved non-identifier. Copy/paste artefact?
120449view00:04, 3 December 2021Khanspersupdated some xrefs
120448view23:54, 2 December 2021KhanspersOntology Term : 'pentose phosphate pathway' added !
120447view23:52, 2 December 2021Khanspersadded xrefs
118988view06:55, 7 June 2021Fehrhartmade pathway nodes clickable by adding shapes
116685view14:16, 9 May 2021EweitzModified title
115245view17:23, 7 February 2021EgonwThese are not mim-conversions.
115104view18:29, 25 January 2021RickHendriks1999
115103view18:20, 25 January 2021RickHendriks1999
115101view18:14, 25 January 2021RickHendriks1999
114606view13:43, 25 January 2021RickHendriks1999New pathway

External references


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NameTypeDatabase referenceComment
5-phospho-D-ribose-1-pyrophosphoric acidMetabolite
6-Phospho-D-gluconateMetaboliteCHEBI:48928 (ChEBI)
6-phosphogluconolactonaseProteinM0R0U3 (Uniprot-TrEMBL)
6-phosphogluconolactonate dehydrogenaseProtein
AMPMetaboliteCHEBI:16027 (ChEBI)
ATPMetaboliteCHEBI:30616 (ChEBI)
D-Erythrose-4-phosphateMetabolite585-18-2 (CAS)
D-Fructose-6-PhosphateMetaboliteQ27096303 (Wikidata)
D-Glucose-6-PhosphateMetabolite59-56-3 (CAS)
D-Ribose-5-phosphateMetabolite3615-55-2 (CAS)
D-Ribulose-5-phosphateProteinC9J9T0 (Uniprot-TrEMBL)
D-Xylulose-5-phosphateMetaboliteCHEBI:16332 (ChEBI)
D-glucono-1,5-lactone-6-phosphateMetabolite2641-81-8 (CAS)
D-glyceraldehyde-3-phosphateMetaboliteCHEBI:70817 (ChEBI)
D-glyceraldehyde-3-phosphateMetaboliteQ26992303 (Wikidata)
D-ribose-1-phosphateMetaboliteCHEBI:48462 (ChEBI)
D-sedoheptulose-7-phosphateMetabolite2646-35-7 (CAS)
Deoxyribose-phophate aldolaseGeneProductENSG00000023697 (Ensembl)
G6PDGeneProductENSG00000160211 (Ensembl)
GlycolysisPathwayWP534 (WikiPathways)
H+MetaboliteCHEBI:15378 (ChEBI)
NADP+MetaboliteCHEBI:18009 (ChEBI)
NADPHMetaboliteHMDB00221 (HMDB)
Oncogene Induced SenescencePathwayWP3308 (WikiPathways)
PE-Induced SenescencePathway
Purine metabolismPathwayWP4792 (WikiPathways)
Pyrimidine metabolismPathwayWP4022 (WikiPathways)
Ribose phophate isomeraseGeneProductENSG00000153574 (Ensembl)
Ribose-phosphate pyrophosphokinaseProteinA0A0B4J207 (Uniprot-TrEMBL)
Ribulose-phosphate 3-epimeraseGeneProductENSG00000197713 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)
TransaldolaseProteinA0A140VK56 (Uniprot-TrEMBL)
TransketolaseProteinA0A0B4J1R6 (Uniprot-TrEMBL)
[CO2]MetaboliteCHEBI:16526 (ChEBI)
acetaldehydeMetaboliteCHEBI:15343 (ChEBI)

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