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Revisión del 17:01 21 abr 2013

La denominación de efecto Warburg se utiliza en realidad para dos tipos de efectos bioquímicos no relacionados. Uno observable en la fisiología de las plantas y otro relacionado a la oncología. Ambas expresiones son debidas al ganador del premio Nobel Otto Heinrich Warburg.

Historia

En 1942 Otto Warburg descubrió que las células normales metabolizan la glucosa de forma distinta a las células cancerígenas. Esto, se puede explicar porque las células cancerosas en presencia de oxígeno tienen tasas glucolíticas mucho más altas de lo normal. Con base en lo anterior, Warburg planteo la teoría de que la función bioenergética de la mitocondria de la célula tumoral está alterada, además, basado en el Efecto Pasteur, en el cual se pronostica que el flujo metabólico de la glucólisis en células aerobias, determinado por el aumento del uso de glucosa y/o por el aumento en la producción de lactato, depende de la energía metabólica que aporta la fosforilación oxidativa de la mitocondira en ATP. Es decir, si se origina una restricción en el aporte de energía metabólica mitocondrial, no sólo por la deficiencia de oxígeno disponible en la célula sino también por una alteración genética que daña la actividad normal de la fosforilación oxidativa de la célula, se debe incrementar el flujo de la glicolisis con el fin de aportar el ATP necesario para suplir las necesidades energéticas de la célula.

Causas

De acuerdo con lo dicho, todos los defectos en el metabolismo aeróbico de la célula puede ser causante de cáncer, los cuales pueden producirse debido a causas genéticas o carcinógenos. En el primer aspecto, la deficiencia de un gen comprometido en la producción de enzimas utilizadas en el transporte de oxígeno (los cuales se originan en el núcleo de la célula) o en el ciclo de Krebs (los cuales se originan en el ADN mitocondrial) forma células cancerígenas u oncogenes. Por otra parte, los carcinógenos, que son sustancias capaces de producir cáncer, inhiben alguna de las etapas aeróbicas del metabolismo, incapacitando el uso de oxígeno por la célula.

Dato adicional

En consecuencia, las células anaeróbicas no desarrollan cáncer pues no tienen mitocondria y son dependientes únicamente de la glicólisis. Por ejemplo, el cristalino, la córnea, algunas partes de la retina y los glóbulos rojos.

Referencias

Vander Heiden, M., Cantley, L., & Thompson, C. (2009). Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation Science, URL: http://www.biounalm.com/2009/05/entendiendo-el-efecto-warburg.html

Leer más: http://www.biounalm.com/2009/05/entendiendo-el-efecto-warburg.html#ixzz2CDDpyvt6 Under Creative Commons License: Attribution Non-Commercial Share Alike

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  {{wikificar|t=20121127061349|Medicina}}
+La denominación de '''efecto Warburg''' se utiliza en realidad para dos tipos de efectos [[bioquímica|bioquímicos]] no relacionados. Uno observable en la [[fisiología]] de las [[planta]]s y otro relacionado a la [[oncología]]. Ambas expresiones son debidas al ganador del premio Nobel [[Otto Heinrich Warburg]].
-'''Efecto Warburg''', es la alteración de la función bioenergética de la mitocondria de la célula cancerígena.
+<!--
+==Fisiología de las plantas==
+En fisiología vegetal, el efecto Warburg hace referencia a la inhibición de la [[fijación de carbono]], y la consecuente inhibición de la [[fotosíntesis]], causada por altas concentraciones de [[oxígeno]].
+La principal responsable de este efecto es la actividad [[oxigenasa]] de la enzima [[RuBisCO]], la cual inicia el proceso de [[fotorrespiración]].
+==Oncology==
+===Basis===
+In oncology, the Warburg effect is the observation that most [[cancer]] cells predominantly produce energy by a high rate of [[glycolysis]] followed by [[lactic acid fermentation]] in the [[cytosol]], rather than by a comparatively low rate of glycolysis followed by oxidation of [[pyruvate]] in [[mitochondria]] as in most normal cells.<ref>{{cite journal|last=Gatenby RA|coauthors=Gillies RJ|title=Why do cancers have high aerobic glycolysis?|journal=Nature Reviews Cancer|year=2004|volume=4|issue=11|pmid=15516961}}</ref><ref>{{cite journal |author=Kim JW, Dang CV |title=Cancer's molecular sweet tooth and the Warburg effect |journal=Cancer Res. |volume=66 |issue=18 |pages=8927–8930 |year=2006 |pmid=16982728 |doi=10.1158/0008-5472.CAN-06-1501 |url=http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16982728}}</ref> The latter process is [[Cellular respiration|aerobic]] (uses oxygen). Malignant, rapidly growing [[tumor]] cells typically have glycolytic rates up to 200 times higher than those of their normal tissues of origin; this occurs even if oxygen is plentiful.
+Otto Warburg postulated this change in metabolism is the fundamental cause of cancer,<ref name="pmid13298683">{{cite journal | author = Warburg O | title = On the origin of cancer cells | journal = Science | volume = 123 | issue = 3191 | pages = 309–314 | year = 1956 | pmid = 13298683 | doi = 10.1126/science.123.3191.309 |bibcode = 1956Sci...123..309W }}</ref> a claim now known as the [[Warburg hypothesis]]. Today, [[mutation]]s in [[oncogene]]s and [[tumor suppressor gene]]s are known to be responsible for [[malignant transformation]].<ref>{{cite journal |author=Bertram JS |title=The molecular biology of cancer |journal=Mol. Aspects Med. |volume=21 |issue=6 |pages=167–223 |year=2000 |pmid=11173079 |doi=10.1016/S0098-2997(00)00007-8}}</ref><ref>{{cite journal |author=Grandér D |title=How do mutated oncogenes and tumor suppressor genes cause cancer? |journal=Med. Oncol. |volume=15 |issue=1 |pages=20–26 |year=1998 |pmid=9643526 |doi=10.1007/BF02787340}}</ref>
+===Use in diagnosis===
+The Warburg effect has important medical applications, as high aerobic glycolysis by malignant tumors is used clinically to diagnose and monitor treatment responses of cancers by [[Chemical imaging|imaging]] uptake of [[Fluorodeoxyglucose|2-<sup>18</sup>F-2-deoxyglucose]] (FDG) (a [[radioactive]] modified [[hexokinase]] [[substrate (biochemistry)|substrate]]) with [[positron emission tomography]] (PET).<ref>{{cite web | title=PET Scan: PET Scan Info Reveals ... | url=http://www.petscaninfo.com/ | accessdate=December 5, 2005 }}</ref><ref>{{cite web | title=4320139 549..559 | url=http://biogenomica.com/PDFs/PauwelsPETandHexokinase.pdf | accessdate=December 5, 2005 }}</ref>
+===Possible explanations of the effect===
+The Warburg effect may simply be a consequence of damage to the mitochondria in cancer, or an adaptation to low-oxygen environments within tumors, or a result of cancer genes shutting down the mitochondria because they are involved in the cell's [[apoptosis]] program which would otherwise kill cancerous cells. It may also be an effect associated with cell proliferation. Since glycolysis provides most of the building blocks required for cell proliferation, cancer cells (and normal proliferating cells) have been proposed to need to activate glycolysis, despite the presence of oxygen, to proliferate .<ref>{{cite journal |author=Lopez-Lazaro M |title=The Warburg effect: why and how do cancer cells activate glycolysis in the presence of oxygen? |journal=Anticancer Agents Med. Chem. |volume=8 |issue=3 |pages=305–312 |year=2008 |doi=10.2174/187152008783961932 |pmid=18393789}}</ref>
+Evidence attributes some of the high aerobic glycolytic rates to an overexpressed form of mitochondrially bound [[hexokinase]]<ref>{{cite journal |author=Bustamante E, Pedersen PL |title=High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=74 |issue=9 |pages=3735–3739 |year=1977 |month=September |pmid=198801 |pmc=431708 |url=http://www.pnas.org/cgi/reprint/74/9/3735 |doi=10.1073/pnas.74.9.3735 |bibcode=1977PNAS...74.3735B}}</ref> responsible for driving the high glycolytic activity.
+In March 2008, [[Lewis C. Cantley]] and colleagues at the [[Harvard Medical School]] announced they had identified the [[enzyme]] that gave rise to the Warburg effect.<ref name="pmid18337823">{{cite journal | author = Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, [[Lewis C. Cantley|Cantley LC]] | title = The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth | journal = Nature | volume = 452 | issue = 7184 | pages = 230–233 | year = 2008 | pmid = 18337823 | doi = 10.1038/nature06734 |bibcode = 2008Natur.452..230C }}</ref><ref>{{cite journal |author=Pedersen PL |title=Warburg, me and Hexokinase 2: Multiple discoveries of key molecular events underlying one of cancers' most common phenotypes, the "Warburg Effect", i.e., elevated glycolysis in the presence of oxygen |journal=J. Bioenerg. Biomembr. |volume=39 |issue=3 |pages=211–222 |year=2007 |pmid=17879147 |doi=10.1007/s10863-007-9094-x}}</ref> The researchers stated [[tumor M2-PK]], a form of the [[pyruvate kinase]] enzyme, is produced in all rapidly dividing cells, and is responsible for enabling cancer cells to consume glucose at an accelerated rate; on forcing the cells to switch to pyruvate kinase's alternative form by inhibiting the production of tumor M2-PK, their growth was curbed. The researchers acknowledged the fact that the exact chemistry of glucose metabolism was likely to vary across different forms of cancer; but PKM2 was identified in all of the cancer cells they had tested. This enzyme form is not usually found in healthy tissue, though it is apparently necessary when cells need to multiply quickly, e.g. in healing wounds or [[hematopoiesis]].
+===Glycolytic inhibitors===
+Many substances have been developed which inhibit glycolysis, and such inhibitors are currently the subject of intense research as anticancer agents,<ref name="pmid16892078">{{cite journal | author = Pelicano H, Martin DS, Xu RH, Huang P | title = Glycolysis inhibition for anticancer treatment | journal = Oncogene | volume = 25 | issue = 34 | pages = 4633–4646 | year = 2006 | pmid = 16892078 | doi = 10.1038/sj.onc.1209597 }}</ref> including SB-204990, [[2-deoxy-D-glucose]] (2DG), [[3-bromopyruvate]] (3-BrPA, bromopyruvic acid, or bromopyruvate), 3-BrOP, 5-thioglucose and [[dichloroacetic acid]] (DCA). Clinical trials are ongoing for 2-DG and DCA.<ref>See [http://clinicaltrials.gov/ct2/show/related/NCT00633087?intr=%222-deoxyglucose%22&rank=1 ClinicalTrials.gov].</ref>
+alpha-cyanocinnamic acid, a monocarbolylate transporter inhibitor has been successfully used as a target in brain tumor research in mice.[http://www.ncbi.nlm.nih.gov/pubmed/21750656 Colen CB]
+DCA, a small-molecule inhibitor of mitochondrial [[pyruvate dehydrogenase kinase]], "downregulates" glycolysis ''[[in vitro]]'' and ''[[in vivo]]''. Researchers at the [[University of Alberta]] theorized in 2007 that DCA might have therapeutic benefits against many types of cancers.<ref name="pmid17222789">{{cite journal | author = Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter CJ, Andrade MA, Thebaud B, Michelakis ED | title = A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth | journal = Cancer Cell | volume = 11 | issue = 1 | pages = 37–51 | year = 2007 | pmid = 17222789 | doi = 10.1016/j.ccr.2006.10.020 }}</ref><ref name="pmid17426345">{{cite journal | author = Pan JG, Mak TW | title = Metabolic targeting as an anticancer strategy: dawn of a new era? | journal = Sci. STKE | volume = 2007 | issue = 381 | pages = pe14–pe14 | year = 2007 | pmid = 17426345 | doi = 10.1126/stke.3812007pe14 }}</ref>
+== Alternative models ==
+A model called the [[reverse Warburg effect]] describes cells producing energy by glycolysis, but were not tumor cells, but  stromal fibroblasts.  Although the Warburg effect would exist in certain cancer types potentially, it highlighted the need for a closer look at tumor metabolism.<ref name="pmid19923890">{{cite journal | author = Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, Pestell RG, Martinez-Outschoorn UE, Sotgia F, Lisanti MP | title = The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma | journal = Cell Cycle | volume = 8 | issue = 23 | pages = 3984–4001 | year = 2009 | month = December | pmid = 19923890 | doi = 10.4161/cc.8.23.10238| url = | issn = }}</ref><ref>Alfarouk KO, Shayoub ME, Muddathir AK, Elhassan GO, Bashir AH. Evolution of Tumor Metabolism might Reflect Carcinogenesis as a Reverse Evolution process (Dismantling of Multicellularity). Cancers. 2011; 3(3):3002-3017.</ref>
+<!--
+==References==
+{{Reflist|2}}
+{{DEFAULTSORT:Warburg Effect}}
+[[Category:Photosynthesis]]
+[[Category:Oncology]]
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 == Referencias ==
+{{reflist|2}}
 * Vander Heiden, M., Cantley, L., & Thompson, C. (2009). Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation Science, URL: http://www.biounalm.com/2009/05/entendiendo-el-efecto-warburg.html