title: Evidence That Does Not Support Pyruvate Kinase M2 (PKM2)-catalyzed Reaction as a Rate-limiting Step in Cancer Cell Glycolysis.
abstract: It has been recognized that the rate-limiting function of pyruvate kinase M2 (PKM2) in glycolysis plays an important role in distributing glycolytic intermediates for anabolic and catabolic purposes in cancer cells. However, after analysis of the catalytic capacity of PKM2 relative to other glycolytic enzymes, the regulation range of PKM2 activity, metabolic flux control, and thermodynamics, we suggest that the PKM2-catalyzed reaction is not a rate-limiting step in cancer cell glycolysis. Hexokinase and phosphofructokinase 1 (PFK1), the first and third enzyme along the pathway, are rate-limiting enzymes that limit the overall glycolytic rate, whereas PKM2 and lactate dehydrogenase, the last two enzymes in the pathway, are for the fast removal of upstream intermediates to prevent the obstruction of the pathway. The argument is in accordance with the catalytic capacity of glycolytic enzymes, regulation range of enzyme activities, metabolic flux control, and thermodynamics.
authors.affiliation: From the Cancer Institute (a Key Laboratory for Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, 310009 Hangzhou and the Biomedical Research Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016 Hangzhou, China.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Xie
authors.affiliation: From the Cancer Institute (a Key Laboratory for Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, 310009 Hangzhou and.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Dai
authors.affiliation: From the Cancer Institute (a Key Laboratory for Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, 310009 Hangzhou and huxun@zju.edu.cn.
authors.forename: Xun
authors.initials: X
authors.lastname: Hu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006019:Glycolysis; D042844:L-Lactate Dehydrogenase (Cytochrome) / Q000235:genetics / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000201:enzymology* / Q000235:genetics; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010732:Phosphofructokinase-1 / Q000235:genetics / Q000378:metabolism; D011770:Pyruvate Kinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D042844:L-Lactate Dehydrogenase (Cytochrome); D010732:Phosphofructokinase-1; D011770:Pyruvate Kinase
keywords: cancer; glycolysis; hexokinase; phosphofructokinase; pyruvate kinase