KEGG   PATHWAY: oaa05230
Entry
oaa05230                    Pathway                                
Name
Central carbon metabolism in cancer - Ornithorhynchus anatinus (platypus)
Description
Malignant transformation of cells requires specific adaptations of cellular metabolism to support growth and survival. In the early twentieth century, Otto Warburg established that there are fundamental differences in the central metabolic pathways operating in malignant tissue. He showed that cancer cells consume a large amount of glucose, maintain high rate of glycolysis and convert a majority of glucose into lactic acid even under normal oxygen concentrations (Warburg's Effects). More recently, it has been recognized that the 'Warburg effect' encompasses a similarly increased utilization of glutamine. From the intermediate molecules provided by enhanced glycolysis and glutaminolysis, cancer cells synthesize most of the macromolecules required for the duplication of their biomass and genome. These cancer-specific alterations represent a major consequence of genetic mutations and the ensuing changes of signalling pathways in cancer cells. Three transcription factors, c-MYC, HIF-1 and p53, are key regulators and coordinate regulation of cancer metabolism in different ways, and many other oncogenes and tumor suppressor genes cluster along the signaling pathways that regulate c-MYC, HIF-1 and p53.
Class
Human Diseases; Cancer: overview
Pathway map
oaa05230  Central carbon metabolism in cancer
oaa05230

Organism
Ornithorhynchus anatinus (platypus) [GN:oaa]
Gene
100074548  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 isoform X1 [KO:K07299]
100086793  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
100091176  hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
114815128  LOW QUALITY PROTEIN: hexokinase-4-like [KO:K12407] [EC:2.7.1.2]
100084782  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
100083539  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
100090171  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
100084173  PDK1; LOW QUALITY PROTEIN: pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial [KO:K12077] [EC:2.7.11.2]
100092821  TP53; cellular tumor antigen p53 [KO:K04451]
100091288  protein SCO2 homolog, mitochondrial [KO:K23755]
100682209  SLC1A5; neutral amino acid transporter B(0) [KO:K05616]
100089118  SIRT3; NAD-dependent protein deacetylase sirtuin-3, mitochondrial isoform X2 [KO:K11413] [EC:2.3.1.286]
100089770  SLC16A3; monocarboxylate transporter 4 [KO:K08180]
100091769  SIRT6; NAD-dependent protein deacetylase sirtuin-6 isoform X1 [KO:K11416] [EC:2.3.1.286]
100079391  MYC; myc proto-oncogene protein [KO:K04377]
100080039  HIF1A; hypoxia-inducible factor 1-alpha isoform X1 [KO:K08268]
100075317  KIT; mast/stem cell growth factor receptor Kit isoform X1 [KO:K05091] [EC:2.7.10.1]
100079345  MET; hepatocyte growth factor receptor precursor [KO:K05099] [EC:2.7.10.1]
100076319  RET; proto-oncogene tyrosine-protein kinase receptor Ret [KO:K05126] [EC:2.7.10.1]
100075894  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
100091139  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
103167743  high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
100078146  NTRK3; NT-3 growth factor receptor isoform X1 [KO:K05101] [EC:2.7.10.1]
100084432  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
100079459  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
100074240  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
100084641  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
100084071  FGFR3; fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
100090467  FLT3; LOW QUALITY PROTEIN: receptor-type tyrosine-protein kinase FLT3 [KO:K05092] [EC:2.7.10.1]
114809992  HRAS; GTPase HRas [KO:K02833]
100085430  KRAS; GTPase KRas isoform X1 [KO:K07827]
100074671  NRAS; GTPase NRas [KO:K07828]
100089456  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100080362  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100087942  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100085480  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100086487  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100088607  GLS; glutaminase kidney isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
103169199  GLS2; glutaminase liver isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
100073461  G6PD; glucose-6-phosphate 1-dehydrogenase isoform X2 [KO:K00036] [EC:1.1.1.49 1.1.1.363]
100088018  HKDC1; hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
100085443  HK1; hexokinase-1 isoform X1 [KO:K00844] [EC:2.7.1.1]
100074718  HK2; LOW QUALITY PROTEIN: hexokinase-2 [KO:K00844] [EC:2.7.1.1]
100079843  HK3; hexokinase-3 isoform X1 [KO:K00844] [EC:2.7.1.1]
100080281  ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
100083239  PFKL; LOW QUALITY PROTEIN: ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
103169433  PFKM; ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
100085823  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
100073834  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
791112  LDHA; L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
100089524  LDHB; L-lactate dehydrogenase B chain isoform X1 [KO:K00016] [EC:1.1.1.27]
100086607  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
100076051  IDH2; isocitrate dehydrogenase [NADP], mitochondrial [KO:K00031] [EC:1.1.1.42]
100080086  IDH1; isocitrate dehydrogenase [NADP] cytoplasmic isoform X1 [KO:K00031] [EC:1.1.1.42]
100088950  TIGAR; fructose-2,6-bisphosphatase TIGAR isoform X1 [KO:K14634] [EC:3.1.3.46]
100074365  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
100086270  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100073788  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100074273  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100080187  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
100082075  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
103167126  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
100083320  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100081473  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100090267  AKT2; RAC-beta serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
100079751  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
100077778  SLC7A5; LOW QUALITY PROTEIN: large neutral amino acids transporter small subunit 1 [KO:K13780]
Compound
C00022  Pyruvate
C00024  Acetyl-CoA
C00025  L-Glutamate
C00026  2-Oxoglutarate
C00031  D-Glucose
C00036  Oxaloacetate
C00037  Glycine
C00041  L-Alanine
C00042  Succinate
C00049  L-Aspartate
C00062  L-Arginine
C00064  L-Glutamine
C00065  L-Serine
C00073  L-Methionine
C00074  Phosphoenolpyruvate
C00078  L-Tryptophan
C00079  L-Phenylalanine
C00082  L-Tyrosine
C00085  D-Fructose 6-phosphate
C00092  D-Glucose 6-phosphate
C00097  L-Cysteine
C00122  Fumarate
C00123  L-Leucine
C00135  L-Histidine
C00148  L-Proline
C00149  (S)-Malate
C00152  L-Asparagine
C00158  Citrate
C00183  L-Valine
C00186  (S)-Lactate
C00197  3-Phospho-D-glycerate
C00311  Isocitrate
C00354  D-Fructose 1,6-bisphosphate
C00407  L-Isoleucine
C00631  2-Phospho-D-glycerate
C00665  beta-D-Fructose 2,6-bisphosphate
C00704  Superoxide
Reference
  Authors
Soga T
  Title
Cancer metabolism: key players in metabolic reprogramming.
  Journal
Cancer Sci 104:275-81 (2013)
DOI:10.1111/cas.12085
Reference
  Authors
Vander Heiden MG, Cantley LC, Thompson CB
  Title
Understanding the Warburg effect: the metabolic requirements of cell proliferation.
  Journal
Science 324:1029-33 (2009)
DOI:10.1126/science.1160809
Reference
  Authors
Teicher BA, Linehan WM, Helman LJ
  Title
Targeting cancer metabolism.
  Journal
Clin Cancer Res 18:5537-45 (2012)
DOI:10.1158/1078-0432.CCR-12-2587
Reference
  Authors
Levine AJ, Puzio-Kuter AM
  Title
The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes.
  Journal
Science 330:1340-4 (2010)
DOI:10.1126/science.1193494
Reference
  Authors
Amoedo ND, Valencia JP, Rodrigues MF, Galina A, Rumjanek FD
  Title
How does the metabolism of tumour cells differ from that of normal cells.
  Journal
Biosci Rep 33:e00080 (2013)
DOI:10.1042/BSR20130066
Reference
  Authors
Cairns RA, Harris IS, Mak TW
  Title
Regulation of cancer cell metabolism.
  Journal
Nat Rev Cancer 11:85-95 (2011)
DOI:10.1038/nrc2981
Reference
  Authors
Munoz-Pinedo C, El Mjiyad N, Ricci JE
  Title
Cancer metabolism: current perspectives and future directions.
  Journal
Cell Death Dis 3:e248 (2012)
DOI:10.1038/cddis.2011.123
Reference
  Authors
Cairns RA, Harris I, McCracken S, Mak TW
  Title
Cancer cell metabolism.
  Journal
Cold Spring Harb Symp Quant Biol 76:299-311 (2011)
DOI:10.1101/sqb.2011.76.012856
Reference
  Authors
Kroemer G, Pouyssegur J
  Title
Tumor cell metabolism: cancer's Achilles' heel.
  Journal
Cancer Cell 13:472-82 (2008)
DOI:10.1016/j.ccr.2008.05.005
Reference
  Authors
DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB
  Title
The biology of cancer: metabolic reprogramming fuels cell growth and proliferation.
  Journal
Cell Metab 7:11-20 (2008)
DOI:10.1016/j.cmet.2007.10.002
Reference
  Authors
Koppenol WH, Bounds PL, Dang CV
  Title
Otto Warburg's contributions to current concepts of cancer metabolism.
  Journal
Nat Rev Cancer 11:325-37 (2011)
DOI:10.1038/nrc3038
Reference
  Authors
Fogg VC, Lanning NJ, Mackeigan JP
  Title
Mitochondria in cancer: at the crossroads of life and death.
  Journal
Chin J Cancer 30:526-39 (2011)
DOI:10.5732/cjc.011.10018
Reference
  Authors
Kim JW, Dang CV
  Title
Cancer's molecular sweet tooth and the Warburg effect.
  Journal
Cancer Res 66:8927-30 (2006)
DOI:10.1158/0008-5472.CAN-06-1501
Reference
  Authors
Yeung SJ, Pan J, Lee MH
  Title
Roles of p53, MYC and HIF-1 in regulating glycolysis - the seventh hallmark of cancer.
  Journal
Cell Mol Life Sci 65:3981-99 (2008)
DOI:10.1007/s00018-008-8224-x
Reference
  Authors
Li B, Simon MC
  Title
Molecular Pathways: Targeting MYC-induced metabolic reprogramming and oncogenic stress in cancer.
  Journal
Clin Cancer Res 19:5835-41 (2013)
DOI:10.1158/1078-0432.CCR-12-3629
Reference
  Authors
Shen L, Sun X, Fu Z, Yang G, Li J, Yao L
  Title
The fundamental role of the p53 pathway in tumor metabolism and its implication in tumor therapy.
  Journal
Clin Cancer Res 18:1561-7 (2012)
DOI:10.1158/1078-0432.CCR-11-3040
Reference
  Authors
Jones RG, Thompson CB
  Title
Tumor suppressors and cell metabolism: a recipe for cancer growth.
  Journal
Genes Dev 23:537-48 (2009)
DOI:10.1101/gad.1756509
Reference
  Authors
Maddocks OD, Vousden KH
  Title
Metabolic regulation by p53.
  Journal
J Mol Med (Berl) 89:237-45 (2011)
DOI:10.1007/s00109-011-0735-5
Reference
  Authors
Chen JQ, Russo J
  Title
Dysregulation of glucose transport, glycolysis, TCA cycle and glutaminolysis by oncogenes and tumor suppressors in cancer cells.
  Journal
Biochim Biophys Acta 1826:370-84 (2012)
DOI:10.1016/j.bbcan.2012.06.004
Reference
  Authors
Kaelin WG Jr, Thompson CB
  Title
Q&A: Cancer: clues from cell metabolism.
  Journal
Nature 465:562-4 (2010)
DOI:10.1038/465562a
Reference
  Authors
Galluzzi L, Kepp O, Vander Heiden MG, Kroemer G
  Title
Metabolic targets for cancer therapy.
  Journal
Nat Rev Drug Discov 12:829-46 (2013)
DOI:10.1038/nrd4145
Reference
  Authors
Phan LM, Yeung SC, Lee MH
  Title
Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies.
  Journal
Cancer Biol Med 11:1-19 (2014)
DOI:10.7497/j.issn.2095-3941.2014.01.001
Reference
  Authors
Icard P, Poulain L, Lincet H
  Title
Understanding the central role of citrate in the metabolism of cancer cells.
  Journal
Biochim Biophys Acta 1825:111-6 (2012)
DOI:10.1016/j.bbcan.2011.10.007
Reference
  Authors
Daye D, Wellen KE
  Title
Metabolic reprogramming in cancer: unraveling the role of glutamine in tumorigenesis.
  Journal
Semin Cell Dev Biol 23:362-9 (2012)
DOI:10.1016/j.semcdb.2012.02.002
Reference
  Authors
Chiarugi A, Dolle C, Felici R, Ziegler M
  Title
The NAD metabolome--a key determinant of cancer cell biology.
  Journal
Nat Rev Cancer 12:741-52 (2012)
DOI:10.1038/nrc3340
Reference
  Authors
Guarente L
  Title
The many faces of sirtuins: Sirtuins and the Warburg effect.
  Journal
Nat Med 20:24-5 (2014)
DOI:10.1038/nm.3438
Reference
  Authors
Fuchs BC, Bode BP
  Title
Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime?
  Journal
Semin Cancer Biol 15:254-66 (2005)
DOI:10.1016/j.semcancer.2005.04.005
Related
pathway
oaa00010  Glycolysis / Gluconeogenesis
oaa00020  Citrate cycle (TCA cycle)
oaa00030  Pentose phosphate pathway
oaa00190  Oxidative phosphorylation
oaa00250  Alanine, aspartate and glutamate metabolism
oaa00260  Glycine, serine and threonine metabolism
oaa00330  Arginine and proline metabolism
oaa01212  Fatty acid metabolism
oaa04010  MAPK signaling pathway
oaa04066  HIF-1 signaling pathway
oaa04150  mTOR signaling pathway
oaa04151  PI3K-Akt signaling pathway
KO pathway
ko05230   
LinkDB

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