KEGG   PATHWAY: myd05230
Entry
myd05230                    Pathway                                
Name
Central carbon metabolism in cancer - Myotis davidii (David's myotis)
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
myd05230  Central carbon metabolism in cancer
myd05230

Organism
Myotis davidii (David's myotis) [GN:myd]
Gene
102766250  SLC2A1; solute carrier family 2 member 1 [KO:K07299]
102773357  SLC2A2; solute carrier family 2 member 2 [KO:K07593]
102757162  GCK; glucokinase [KO:K12407] [EC:2.7.1.2]
102757844  PKM; pyruvate kinase, muscle [KO:K00873] [EC:2.7.1.40]
102759810  PDHA2; pyruvate dehydrogenase (lipoamide) alpha 2 [KO:K00161] [EC:1.2.4.1]
102771346  PDHA1; pyruvate dehydrogenase (lipoamide) alpha 1 [KO:K00161] [EC:1.2.4.1]
102775559  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial-like [KO:K00161] [EC:1.2.4.1]
102765778  PDHB; pyruvate dehydrogenase (lipoamide) beta [KO:K00162] [EC:1.2.4.1]
102767099  PDK1; pyruvate dehydrogenase kinase 1 [KO:K12077] [EC:2.7.11.2]
102759012  TP53; tumor protein p53 [KO:K04451]
102764105  protein SCO2 homolog, mitochondrial [KO:K23755]
102773458  SLC1A5; solute carrier family 1 member 5 [KO:K05616]
102762288  SLC16A3; solute carrier family 16 member 3 [KO:K08180]
102757008  SIRT6; sirtuin 6 [KO:K11416] [EC:2.3.1.286]
102758544  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
102751343  HIF1A; hypoxia inducible factor 1 alpha subunit [KO:K08268]
102761085  KIT; KIT proto-oncogene receptor tyrosine kinase [KO:K05091] [EC:2.7.10.1]
102753524  hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
102766212  RET; ret proto-oncogene [KO:K05126] [EC:2.7.10.1]
102775204  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102771013  ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
102765751  NTRK1; neurotrophic receptor tyrosine kinase 1 [KO:K03176] [EC:2.7.10.1]
102761142  NTRK3; neurotrophic receptor tyrosine kinase 3 [KO:K05101] [EC:2.7.10.1]
102761943  PDGFRA; platelet derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
102764172  PDGFRB; platelet derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
102759202  FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
102763283  FGFR2; fibroblast growth factor receptor 2 [KO:K05093] [EC:2.7.10.1]
102760103  FLT3; fms related tyrosine kinase 3 [KO:K05092] [EC:2.7.10.1]
102762537  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102762284  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102761492  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102772748  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102763997  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102757282  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102769037  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102775211  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102767571  GLS2; glutaminase 2 [KO:K01425] [EC:3.5.1.2]
102767787  GLS; glutaminase [KO:K01425] [EC:3.5.1.2]
102773111  G6PD; glucose-6-phosphate dehydrogenase [KO:K00036] [EC:1.1.1.49 1.1.1.363]
102767710  HK2; hexokinase 2 [KO:K00844] [EC:2.7.1.1]
102762722  HKDC1; hexokinase domain containing 1 [KO:K00844] [EC:2.7.1.1]
102763004  HK1; hexokinase 1 [KO:K00844] [EC:2.7.1.1]
102760926  HK3; hexokinase 3 [KO:K00844] [EC:2.7.1.1]
102768013  PFKM; phosphofructokinase, muscle [KO:K00850] [EC:2.7.1.11]
102753287  PFKP; phosphofructokinase, platelet [KO:K00850] [EC:2.7.1.11]
102757968  PFKL; phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
102767554  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
102765769  phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
102768445  phosphoglycerate mutase 2-like [KO:K01834] [EC:5.4.2.11]
102751910  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
102769155  L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
102771185  LDHB; lactate dehydrogenase B [KO:K00016] [EC:1.1.1.27]
102752057  L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
102763713  LDHA; lactate dehydrogenase A [KO:K00016] [EC:1.1.1.27]
102764188  LDHC; L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
102757893  IDH1; isocitrate dehydrogenase (NADP(+)) 1, cytosolic [KO:K00031] [EC:1.1.1.42]
102759038  IDH2; isocitrate dehydrogenase (NADP(+)) 2, mitochondrial [KO:K00031] [EC:1.1.1.42]
102755420  TIGAR; TP53 induced glycolysis regulatory phosphatase [KO:K14634] [EC:3.1.3.46]
102755323  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
102764343  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102766356  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102758951  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
102763670  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102753036  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102760468  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102772266  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102773065  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102766933  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
102761590  SLC7A5; solute carrier family 7 member 5 [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
myd00010  Glycolysis / Gluconeogenesis
myd00020  Citrate cycle (TCA cycle)
myd00030  Pentose phosphate pathway
myd00190  Oxidative phosphorylation
myd00250  Alanine, aspartate and glutamate metabolism
myd00260  Glycine, serine and threonine metabolism
myd00330  Arginine and proline metabolism
myd01212  Fatty acid metabolism
myd04010  MAPK signaling pathway
myd04066  HIF-1 signaling pathway
myd04150  mTOR signaling pathway
myd04151  PI3K-Akt signaling pathway
KO pathway
ko05230   
LinkDB

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