Pentose phosphate pathway in senescent cells (Homo sapiens)

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1, 3-52Lower levels of the NADP+/NADPH ratioupregulate the regenartion of NADPH.ATPNADP+GlycolysisD-Fructose-6-PhosphateD-Erythrose-4-phosphateNADP+/NADPHNADPH2-deoxy-D-ribose-5-phosphate6-Phospho-D-gluconateTransketolase6-phosphogluconolactonasePyrimidine metabolismNADPH5-phospho-D-ribose-1-pyrophosphoric acidTransaldolaseD-sedoheptulose-7-phosphatePhosphoglucomutaseD-glucono-1,5-lactone-6-phosphateRibulose-phosphate-3-epimeraseD-glyceraldehyde-3-phosphateOncogene Induced SenescenceDeoxyribose-phophate aldolaseglucose-6-phosphate 1-dehydrogenaseD-Glucose-6-PhosphateOncogene Induced Senescencep53NADP+Purine metabolismD-Xylulose-5-phosphateD-Ribulose-5-phosphate[CO2]D-Fructose-6-PhosphateRibose-phosphate pyrophosphokinaseD-glyceraldehyde-3-phosphateAMPH+TransketolaseD-ribose-1-phosphate6-phosphogluconolactonate dehydrogenasePE-Induced SenescenceH+acetaldehydeD-Ribose-5-phosphateRibose phophate isomerase


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. Birgit Veldman; ''Metabolic hallmarks of cellular senescence: highlighting the role of intracellular pathways in various senescent phenotypes''; , 2020
  2. 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
  3. 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
  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. 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


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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 aldolaseProtein
GlycolysisPathwayWP534 (WikiPathways)
H+MetaboliteCHEBI:15378 (ChEBI)
NADP+MetaboliteCHEBI:18009 (ChEBI)
NADPHMetaboliteHMDB00221 (HMDB)
Oncogene Induced SenescencePathwayWP3308 (WikiPathways)
PE-Induced SenescencePathway
PhosphoglucomutaseProteinE7ENQ8 (Uniprot-TrEMBL)
Purine metabolismPathwayWP4792 (WikiPathways)
Pyrimidine metabolismPathwayWP4022 (WikiPathways)
Ribose phophate isomeraseProtein
Ribose-phosphate pyrophosphokinaseProteinA0A0B4J207 (Uniprot-TrEMBL)
TransaldolaseProteinA0A140VK56 (Uniprot-TrEMBL)
TransketolaseProteinA0A0B4J1R6 (Uniprot-TrEMBL)
[CO2]MetaboliteCHEBI:16526 (ChEBI)
acetaldehydeMetaboliteCHEBI:15343 (ChEBI)
glucose-6-phosphate 1-dehydrogenaseProtein
p53MetaboliteCHEBI:77731 (ChEBI)

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