Editing Glycolysis (section)

=== Cancer ===
Malignant tumor cells perform glycolysis at a rate that is ten times faster than their noncancerous tissue counterparts.<ref>{{cite journal | vauthors = Alfarouk KO, Verduzco D, Rauch C, Muddathir AK, Adil HH, Elhassan GO, Ibrahim ME, David Polo Orozco J, Cardone RA, Reshkin SJ, Harguindey S | title = Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question | journal = Oncoscience | volume = 1 | issue = 12 | pages = 777–802 | date = 2014 | pmid = 25621294 | pmc = 4303887 | doi = 10.18632/oncoscience.109 }}</ref> During their genesis, limited capillary support often results in hypoxia (decreased O2 supply) within the tumor cells. Thus, these cells rely on anaerobic metabolic processes such as glycolysis for ATP (adenosine triphosphate). Some tumor cells overexpress specific glycolytic enzymes which result in higher rates of glycolysis.<ref>{{cite journal | vauthors = Alfarouk KO, Shayoub ME, Muddathir AK, Elhassan GO, Bashir AH | title = Evolution of Tumor Metabolism might Reflect Carcinogenesis as a Reverse Evolution process (Dismantling of Multicellularity) | journal = Cancers | volume = 3 | issue = 3 | pages = 3002–3017 | date = July 2011 | pmid = 24310356 | pmc = 3759183 | doi = 10.3390/cancers3033002 | doi-access = free }}</ref> Often these enzymes are Isoenzymes, of traditional glycolysis enzymes, that vary in their susceptibility to traditional feedback inhibition. The increase in glycolytic activity ultimately counteracts the effects of hypoxia by generating sufficient ATP from this anaerobic pathway.<ref>{{cite book | vauthors = Nelson DL, Cox MM |title=Lehninger principles of biochemistry |date=2005 |publisher=W.H. Freeman |location=New York |isbn=978-0-7167-4339-2 |edition=4th |url=https://archive.org/details/lehningerprincip00lehn_0}}</ref> This phenomenon was first described in 1930 by [[Otto Heinrich Warburg|Otto Warburg]] and is referred to as the [[Warburg effect (oncology)|Warburg effect]]. The [[Warburg hypothesis]] claims that cancer is primarily caused by dysfunctionality in mitochondrial metabolism, rather than because of the uncontrolled growth of cells.
A number of theories have been advanced to explain the Warburg effect.  One such theory suggests that the increased glycolysis is a normal protective process of the body and that malignant change could be primarily caused by energy metabolism.<ref>{{cite web |title=What is Cancer? |url=http://thepathogenesisofcancer.com/ |access-date=September 8, 2012 |date=October 2011 | vauthors = Gold J |archive-url=https://web.archive.org/web/20180519194539/http://thepathogenesisofcancer.com/ |archive-date=May 19, 2018 |url-status=dead}}</ref>

This high glycolysis rate has important medical applications, as high [[Aerobic fermentation|aerobic glycolysis]] by malignant tumors is utilized clinically to diagnose and monitor treatment responses of [[cancer]]s 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 name="pmid11043392">{{cite journal | vauthors = Pauwels EK, Sturm EJ, Bombardieri E, Cleton FJ, Stokkel MP | title = Positron-emission tomography with [18F]fluorodeoxyglucose. Part I. Biochemical uptake mechanism and its implication for clinical studies | journal = Journal of Cancer Research and Clinical Oncology | volume = 126 | issue = 10 | pages = 549–59 | date = October 2000 | pmid = 11043392 | doi = 10.1007/pl00008465 | s2cid = 2725555 }}</ref><ref>{{cite web | title=PET Scan: PET Scan Info Reveals ... | url=http://www.petscaninfo.com/ | access-date=December 5, 2005 }}</ref>

There is ongoing research to affect mitochondrial metabolism and treat cancer by reducing glycolysis and thus starving cancerous cells in various new ways, including a [[ketogenic diet]].<ref>{{cite journal | vauthors = Schwartz L, Seyfried T, Alfarouk KO, Da Veiga Moreira J, Fais S | title = Out of Warburg effect: An effective cancer treatment targeting the tumor specific metabolism and dysregulated pH | journal = Seminars in Cancer Biology | volume = 43 | pages = 134–138 | date = April 2017 | pmid = 28122260 | doi = 10.1016/j.semcancer.2017.01.005 }}</ref><ref>{{cite journal | vauthors = Schwartz L, Supuran CT, Alfarouk KO | title = The Warburg Effect and the Hallmarks of Cancer | journal = Anti-Cancer Agents in Medicinal Chemistry | volume = 17 | issue = 2 | pages = 164–170 | date = 2017 | pmid = 27804847 | doi = 10.2174/1871520616666161031143301 }}</ref><ref>{{cite journal | vauthors = Maroon J, Bost J, Amos A, Zuccoli G | title = Restricted calorie ketogenic diet for the treatment of glioblastoma multiforme | journal = Journal of Child Neurology | volume = 28 | issue = 8 | pages = 1002–1008 | date = August 2013 | pmid = 23670248 | doi = 10.1177/0883073813488670 | s2cid = 1994087 }}</ref>