KEGG   PATHWAY: chx05230
Entry
chx05230                    Pathway                                
Name
Central carbon metabolism in cancer - Capra hircus (goat)
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
chx05230  Central carbon metabolism in cancer
chx05230

Organism
Capra hircus (goat) [GN:chx]
Gene
102174800  SLC2A1; solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
102176460  SLC2A2; solute carrier family 2, facilitated glucose transporter member 2 [KO:K07593]
102185429  GCK; glucokinase [KO:K12407] [EC:2.7.1.2]
102178731  PKM; pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
102168710  PDHA1; pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
102187468  PDHA2; pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial isoform X1 [KO:K00161] [EC:1.2.4.1]
102184953  PDHB; pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
102186251  PDK1; pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial [KO:K12077] [EC:2.7.11.2]
102169621  TP53; cellular tumor antigen p53 [KO:K04451]
102189751  protein SCO2 homolog, mitochondrial [KO:K23755]
102176550  SLC1A5; LOW QUALITY PROTEIN: neutral amino acid transporter B(0) [KO:K05616]
102181661  SIRT3; NAD-dependent protein deacetylase sirtuin-3, mitochondrial isoform X1 [KO:K11413] [EC:2.3.1.286]
102177468  SLC16A3; monocarboxylate transporter 4 [KO:K08180]
102174381  SIRT6; NAD-dependent protein deacetylase sirtuin-6 isoform X1 [KO:K11416] [EC:2.3.1.286]
102171262  MYC; myc proto-oncogene protein [KO:K04377]
100861391  HIF1A; hypoxia-inducible factor 1-alpha [KO:K08268]
100861386  KIT; mast/stem cell growth factor receptor Kit precursor [KO:K05091] [EC:2.7.10.1]
102181186  MET; hepatocyte growth factor receptor isoform X2 [KO:K05099] [EC:2.7.10.1]
102172412  RET; proto-oncogene tyrosine-protein kinase receptor Ret [KO:K05126] [EC:2.7.10.1]
102172767  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102181989  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
102172584  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
102185689  NTRK3; NT-3 growth factor receptor isoform X1 [KO:K05101] [EC:2.7.10.1]
102174007  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
102184426  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
102180282  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
102170938  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
102189319  FLT3; receptor-type tyrosine-protein kinase FLT3 [KO:K05092] [EC:2.7.10.1]
102186668  HRAS; GTPase HRas isoform X1 [KO:K02833]
102172519  KRAS; GTPase KRas isoform X1 [KO:K07827]
102187180  NRAS; GTPase NRas [KO:K07828]
108638619  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
102190520  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X4 [KO:K04368] [EC:2.7.12.2]
102175285  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102186040  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102188824  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102188907  GLS; glutaminase kidney isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
102188116  GLS2; glutaminase liver isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
102171321  G6PD; glucose-6-phosphate 1-dehydrogenase isoform X1 [KO:K00036] [EC:1.1.1.49 1.1.1.363]
102168356  HK2; hexokinase-2 [KO:K00844] [EC:2.7.1.1]
102182403  HK3; hexokinase-3 isoform X1 [KO:K00844] [EC:2.7.1.1]
102190759  HK1; hexokinase-1 [KO:K00844] [EC:2.7.1.1]
102189736  HKDC1; putative hexokinase HKDC1 isoform X1 [KO:K00844] [EC:2.7.1.1]
102187810  ATP-dependent 6-phosphofructokinase, liver type [KO:K00850] [EC:2.7.1.11]
102186091  PFKM; ATP-dependent 6-phosphofructokinase, muscle type [KO:K00850] [EC:2.7.1.11]
102190144  PFKP; ATP-dependent 6-phosphofructokinase, platelet type [KO:K00850] [EC:2.7.1.11]
102188713  LOW QUALITY PROTEIN: phosphoglycerate mutase 1-like [KO:K01834] [EC:5.4.2.11]
102169807  PGAM2; phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
102171124  PGAM1; phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
100860870  LDH-A; lactate dehydrogenase [KO:K00016] [EC:1.1.1.27]
102188750  LDHB; L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
102178360  LDHAL6B; L-lactate dehydrogenase A-like 6B [KO:K00016] [EC:1.1.1.27]
102189835  L-lactate dehydrogenase C chain isoform X2 [KO:K00016] [EC:1.1.1.27]
102190002  IDH1; isocitrate dehydrogenase [NADP] cytoplasmic [KO:K00031] [EC:1.1.1.42]
102168943  IDH2; isocitrate dehydrogenase [NADP], mitochondrial [KO:K00031] [EC:1.1.1.42]
102169167  TIGAR; fructose-2,6-bisphosphatase TIGAR [KO:K14634] [EC:3.1.3.46]
102185891  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X2 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
102185042  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102168391  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102177551  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102179343  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102170135  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
102188710  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100860904  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102174051  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102187521  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100860902  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
102186985  SLC7A5; 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
chx00010  Glycolysis / Gluconeogenesis
chx00020  Citrate cycle (TCA cycle)
chx00030  Pentose phosphate pathway
chx00190  Oxidative phosphorylation
chx00250  Alanine, aspartate and glutamate metabolism
chx00260  Glycine, serine and threonine metabolism
chx00330  Arginine and proline metabolism
chx01212  Fatty acid metabolism
chx04010  MAPK signaling pathway
chx04066  HIF-1 signaling pathway
chx04150  mTOR signaling pathway
chx04151  PI3K-Akt signaling pathway
KO pathway
ko05230   
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