KEGG   PATHWAY: lruf05230
Entry
lruf05230                   Pathway                                
Name
Central carbon metabolism in cancer - Lynx rufus (bobcat)
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
lruf05230  Central carbon metabolism in cancer
lruf05230

Organism
Lynx rufus (bobcat) [GN:lruf]
Gene
124515644  solute carrier family 2, facilitated glucose transporter member 1 [KO:K07299]
124526881  solute carrier family 2, facilitated glucose transporter member 2 isoform X1 [KO:K07593]
124524269  hexokinase-4 isoform X1 [KO:K12407] [EC:2.7.1.2]
124508427  pyruvate kinase PKM isoform X1 [KO:K00873] [EC:2.7.1.40]
124521338  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial-like isoform X1 [KO:K00161] [EC:1.2.4.1]
124509400  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial [KO:K00161] [EC:1.2.4.1]
124513865  pyruvate dehydrogenase E1 component subunit beta, mitochondrial-like [KO:K00162] [EC:1.2.4.1]
124522839  pyruvate dehydrogenase E1 component subunit beta, mitochondrial [KO:K00162] [EC:1.2.4.1]
124515707  pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial [KO:K12077] [EC:2.7.11.2]
124519563  cellular tumor antigen p53 isoform X1 [KO:K04451]
124501287  protein SCO2 homolog, mitochondrial [KO:K23755]
124510990  neutral amino acid transporter B(0) [KO:K05616]
124527515  NAD-dependent protein deacetylase sirtuin-3, mitochondrial-like isoform X1 [KO:K11413] [EC:2.3.1.286]
124522549  monocarboxylate transporter 4 [KO:K08180]
124524206  NAD-dependent protein deacetylase sirtuin-6 [KO:K11416] [EC:2.3.1.286]
124507805  myc proto-oncogene protein [KO:K04377]
124512137  hypoxia-inducible factor 1-alpha [KO:K08268]
124520981  mast/stem cell growth factor receptor Kit [KO:K05091] [EC:2.7.10.1]
124524670  hepatocyte growth factor receptor [KO:K05099] [EC:2.7.10.1]
124506146  proto-oncogene tyrosine-protein kinase receptor Ret [KO:K05126] [EC:2.7.10.1]
124523868  epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
124513327  receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
124521817  high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
124517372  NT-3 growth factor receptor isoform X1 [KO:K05101] [EC:2.7.10.1]
124520247  platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
124507266  platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
124520453  LOW QUALITY PROTEIN: fibroblast growth factor receptor 1-like [KO:K04362] [EC:2.7.10.1]
124506756  LOW QUALITY PROTEIN: fibroblast growth factor receptor 2-like [KO:K05093] [EC:2.7.10.1]
124522669  fibroblast growth factor receptor 3 isoform X1 [KO:K05094] [EC:2.7.10.1]
124511181  receptor-type tyrosine-protein kinase FLT3 [KO:K05092] [EC:2.7.10.1]
124527565  GTPase HRas isoform X1 [KO:K02833]
124502703  GTPase KRas isoform X1 [KO:K07827]
124516245  GTPase NRas [KO:K07828]
124523760  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
124508471  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
124524782  dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
124517731  mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
124519861  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
124501522  glutaminase liver isoform, mitochondrial [KO:K01425] [EC:3.5.1.2]
124515981  glutaminase kidney isoform, mitochondrial isoform X1 [KO:K01425] [EC:3.5.1.2]
124525845  glucose-6-phosphate 1-dehydrogenase isoform X1 [KO:K00036] [EC:1.1.1.49 1.1.1.363]
124520100  hexokinase-3 [KO:K00844] [EC:2.7.1.1]
124503380  hexokinase-2 [KO:K00844] [EC:2.7.1.1]
124505861  hexokinase HKDC1 [KO:K00844] [EC:2.7.1.1]
124506865  hexokinase-1 isoform X1 [KO:K00844] [EC:2.7.1.1]
124526236  ATP-dependent 6-phosphofructokinase, liver type isoform X1 [KO:K00850] [EC:2.7.1.11]
124501338  ATP-dependent 6-phosphofructokinase, muscle type isoform X1 [KO:K00850] [EC:2.7.1.11]
124502465  ATP-dependent 6-phosphofructokinase, platelet type isoform X1 [KO:K00850] [EC:2.7.1.11]
124507030  phosphoglycerate mutase 1 [KO:K01834] [EC:5.4.2.11]
124523676  phosphoglycerate mutase 2 [KO:K01834] [EC:5.4.2.11]
124505110  L-lactate dehydrogenase A chain [KO:K00016] [EC:1.1.1.27]
124505180  L-lactate dehydrogenase B chain-like isoform X1 [KO:K00016] [EC:1.1.1.27]
124506216  L-lactate dehydrogenase C chain [KO:K00016] [EC:1.1.1.27]
124528295  L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
124507753  LOW QUALITY PROTEIN: L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
124529375  L-lactate dehydrogenase A-like 6A [KO:K00016] [EC:1.1.1.27]
124502309  L-lactate dehydrogenase B chain [KO:K00016] [EC:1.1.1.27]
124509583  L-lactate dehydrogenase A chain-like [KO:K00016] [EC:1.1.1.27]
124517345  isocitrate dehydrogenase [NADP], mitochondrial isoform X1 [KO:K00031] [EC:1.1.1.42]
124515930  isocitrate dehydrogenase [NADP] cytoplasmic [KO:K00031] [EC:1.1.1.42]
124501055  fructose-2,6-bisphosphatase TIGAR [KO:K14634] [EC:3.1.3.46]
124518602  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]
124525968  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
124527077  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
124514827  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
124517840  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
124514527  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
124523730  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
124510270  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
124511119  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124512474  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124514798  serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
124511568  LOW QUALITY PROTEIN: large neutral amino acids transporter small subunit 1-like [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
lruf00010  Glycolysis / Gluconeogenesis
lruf00020  Citrate cycle (TCA cycle)
lruf00030  Pentose phosphate pathway
lruf00190  Oxidative phosphorylation
lruf00250  Alanine, aspartate and glutamate metabolism
lruf00260  Glycine, serine and threonine metabolism
lruf00330  Arginine and proline metabolism
lruf01212  Fatty acid metabolism
lruf04010  MAPK signaling pathway
lruf04066  HIF-1 signaling pathway
lruf04150  mTOR signaling pathway
lruf04151  PI3K-Akt signaling pathway
KO pathway
ko05230   
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