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Pathway Description
Warburg Effect
Bos taurus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-10
Last Updated: 2019-08-16
The Warburg Effect refers to the phenomenon that occurs in most cancer cells where instead of generating energy with a low rate of glycolysis followed by oxidizing pyruvate via the Krebs cycle in the mitochondria, the pyruvate from a high rate of glycolysis undergoes lactic acid fermentation in the cytosol. As the Krebs cycle is an aerobic process, in normal cells lactate production is reserved for anaerobic conditions. However, cancer cells preferentially utilize glucose for lactate production via this “aerobic glycolysis”, even when oxygen is plentiful. The Warburg Effect is thought to be the result of mutations to oncogenes and tumour suppressor genes. It may be an adaptation to low-oxygen environments within tumors, the result of cancer genes shutting down the mitochondria, or a mechanism to aid cell proliferation via increased glycolysis. The Warburg Effect involves numerous pathways, including growth factor stimulation, transcriptional activation, and glycolysis promotion.
References
Warburg Effect References
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Pubmed: 2719857
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Pubmed: 1201027
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Pubmed: 7499243
Sonstegard TS, Capuco AV, White J, Van Tassell CP, Connor EE, Cho J, Sultana R, Shade L, Wray JE, Wells KD, Quackenbush J: Analysis of bovine mammary gland EST and functional annotation of the Bos taurus gene index. Mamm Genome. 2002 Jul;13(7):373-9. doi: 10.1007/s00335-001-2145-4.
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Harhay GP, Sonstegard TS, Keele JW, Heaton MP, Clawson ML, Snelling WM, Wiedmann RT, Van Tassell CP, Smith TP: Characterization of 954 bovine full-CDS cDNA sequences. BMC Genomics. 2005 Nov 23;6:166. doi: 10.1186/1471-2164-6-166.
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Ho L, Javed AA, Pepin RA, Thekkumkara TJ, Raefsky C, Mole JE, Caliendo AM, Kwon MS, Kerr DS, Patel MS: Identification of a cDNA clone for the beta-subunit of the pyruvate dehydrogenase component of human pyruvate dehydrogenase complex. Biochem Biophys Res Commun. 1988 Feb 15;150(3):904-8. doi: 10.1016/0006-291x(88)90714-0.
Pubmed: 2829898
Rahmatullah M, Gopalakrishnan S, Andrews PC, Chang CL, Radke GA, Roche TE: Subunit associations in the mammalian pyruvate dehydrogenase complex. Structure and role of protein X and the pyruvate dehydrogenase component binding domain of the dihydrolipoyl transacetylase component. J Biol Chem. 1989 Feb 5;264(4):2221-7.
Pubmed: 2914903
Neagle J, De Marcucci O, Dunbar B, Lindsay JG: Component X of mammalian pyruvate dehydrogenase complex: structural and functional relationship to the lipoate acetyltransferase (E2) component. FEBS Lett. 1989 Aug 14;253(1-2):11-5. doi: 10.1016/0014-5793(89)80919-6.
Pubmed: 2759236
Rice JE, Dunbar B, Lindsay JG: Sequences directing dihydrolipoamide dehydrogenase (E3) binding are located on the 2-oxoglutarate dehydrogenase (E1) component of the mammalian 2-oxoglutarate dehydrogenase multienzyme complex. EMBO J. 1992 Sep;11(9):3229-35.
Pubmed: 1505515
Du J, Zhou Y, Su X, Yu JJ, Khan S, Jiang H, Kim J, Woo J, Kim JH, Choi BH, He B, Chen W, Zhang S, Cerione RA, Auwerx J, Hao Q, Lin H: Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science. 2011 Nov 11;334(6057):806-9. doi: 10.1126/science.1207861.
Pubmed: 22076378
Plank DW, Howard JB: Identification of the reactive sulfhydryl and sequences of cysteinyl-tryptic peptides from beef heart aconitase. J Biol Chem. 1988 Jun 15;263(17):8184-9.
Pubmed: 3372519
Plank DW, Kennedy MC, Beinert H, Howard JB: Cysteine labeling studies of beef heart aconitase containing a 4Fe, a cubane 3Fe, or a linear 3Fe cluster. J Biol Chem. 1989 Dec 5;264(34):20385-93.
Pubmed: 2511202
Lauble H, Kennedy MC, Beinert H, Stout CD: Crystal structures of aconitase with isocitrate and nitroisocitrate bound. Biochemistry. 1992 Mar 17;31(10):2735-48. doi: 10.1021/bi00125a014.
Pubmed: 1547214
Zeng Y, Weiss C, Yao TT, Huang J, Siconolfi-Baez L, Hsu P, Rushbrook JI: Isocitrate dehydrogenase from bovine heart: primary structure of subunit 3/4. Biochem J. 1995 Sep 1;310 ( Pt 2):507-16. doi: 10.1042/bj3100507.
Pubmed: 7654189
Rushbrook JI, Harvey RA: Nicotinamide adenine dinucleotide dependent isocitrate dehydrogenase from beef heart: subunit heterogeneity and enzyme dissociation. Biochemistry. 1978 Dec 12;17(25):5339-46. doi: 10.1021/bi00618a003.
Pubmed: 215197
Weiss C, Zeng Y, Huang J, Sobocka MB, Rushbrook JI: Bovine NAD+-dependent isocitrate dehydrogenase: alternative splicing and tissue-dependent expression of subunit 1. Biochemistry. 2000 Feb 22;39(7):1807-16. doi: 10.1021/bi991691i.
Pubmed: 10677231
Bradford AP, Aitken A, Beg F, Cook KG, Yeaman SJ: Amino acid sequence surrounding the lipoic acid cofactor of bovine kidney 2-oxoglutarate dehydrogenase complex. FEBS Lett. 1987 Sep 28;222(1):211-4. doi: 10.1016/0014-5793(87)80221-1.
Pubmed: 3115829
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000654
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