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dc.contributor.authorMoreno-Sanchez, Rafael
dc.contributor.authorMarin-Hernandez, Alvaro
dc.contributor.authorSaavedra, Emma
dc.contributor.authorPardo, Juan P
dc.contributor.authorRalph, Stephen J
dc.contributor.authorRodriguez-Enriquez, Sara
dc.date.accessioned2018-11-06T04:28:32Z
dc.date.available2018-11-06T04:28:32Z
dc.date.issued2014
dc.identifier.issn1357-2725
dc.identifier.doi10.1016/j.biocel.2014.01.025
dc.identifier.urihttp://hdl.handle.net/10072/102408
dc.description.abstractApplying basic biochemical principles, this review analyzes data that contrasts with the Warburg hypothesis that glycolysis is the exclusive ATP provider in cancer cells. Although disregarded for many years, there is increasing experimental evidence demonstrating that oxidative phosphorylation (OxPhos) makes a significant contribution to ATP supply in many cancer cell types and under a variety of conditions. Substrates oxidized by normal mitochondria such as amino acids and fatty acids are also avidly consumed by cancer cells. In this regard, the proposal that cancer cells metabolize glutamine for anabolic purposes without the need for a functional respiratory chain and OxPhos is analyzed considering thermodynamic and kinetic aspects for the reductive carboxylation of 2-oxoglutarate catalyzed by isocitrate dehydrogenase. In addition, metabolic control analysis (MCA) studies applied to energy metabolism of cancer cells are reevaluated. Regardless of the experimental/environmental conditions and the rate of lactate production, the flux-control of cancer glycolysis is robust in the sense that it involves the same steps: glucose transport, hexokinase, hexosephosphate isomerase and glycogen degradation, all at the beginning of the pathway; these steps together with phosphofructokinase 1 also control glycolysis in normal cells. The respiratory chain complexes exert significantly higher flux-control on OxPhos in cancer cells than in normal cells. Thus, determination of the contribution of each pathway to ATP supply and/or the flux-control distribution of both pathways in cancer cells is necessary in order to identify differences from normal cells which may lead to the design of rational alternative therapies that selectively target cancer energy metabolism.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherPergamon Press
dc.publisher.placeUnited Kingdom
dc.relation.ispartofpagefrom10
dc.relation.ispartofpageto23
dc.relation.ispartofjournalThe International Journal of Biochemistry & Cell Biology
dc.relation.ispartofvolume50
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchBiochemistry and cell biology not elsewhere classified
dc.subject.fieldofresearchMedical biochemistry and metabolomics
dc.subject.fieldofresearchMedical physiology
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode310199
dc.subject.fieldofresearchcode3205
dc.subject.fieldofresearchcode3208
dc.titleWho controls the ATP supply in cancer cells? Biochemistry lessons to understand cancer energy metabolism
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorRalph, Stephen J.


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