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Pyruvate kinase activators for treatment of pyruvate kinase deficiency. [PDF]

Hematology Am Soc Hematol Educ Program, 2023
Pyruvate kinase (PK) deficiency is a congenital hemolytic anemia with wide-ranging clinical symptoms and complications associated with significant morbidity and reduced health-related quality of life in both children and adults.
Grace RF.
europepmc   +4 more sources

Pyruvate Kinase M2 and Cancer: The Role of PKM2 in Promoting Tumorigenesis

Frontiers in Oncology, 2020
Pyruvate kinase plays a pivotal role in regulating cell metabolism. The final and rate-limiting step of glycolysis is the conversion of Phosphoenolpyruvate (PEP) to Pyruvate, which is catalyzed by Pyruvate Kinase. There are four isomeric, tissue-specific
Kulsoom Zahra, Tulika Dey, Ashish, Surendra Pratap Mishra, Uma Pandey   +4 more
doaj   +2 more sources

Protein kinase function of pyruvate kinase M2 and cancer

Cancer Cell International, 2020
Pyruvate kinase is a terminal enzyme in the glycolytic pathway, where it catalyzes the conversion of phosphoenolpyruvate to pyruvate and production of ATP via substrate level phosphorylation.
Xun Chen, Shangwu Chen, Dongsheng Yu
doaj   +2 more sources

Mitapivat versus Placebo for Pyruvate Kinase Deficiency.

New England Journal of Medicine, 2022
BACKGROUND Pyruvate kinase deficiency is a rare, hereditary, chronic condition that is associated with hemolytic anemia. In a phase 2 study, mitapivat, an oral, first-in-class activator of erythrocyte pyruvate kinase, increased the hemoglobin level in ...
Hanny Al‐Samkari, F. Galactéros, A. Glenthøj, J. Rothman, O. Andres, R. Grace, Marta Morado-Arias, D. Layton, Koichi Onodera, M. Verhovsek, W. Barcellini, S. Chonat, M. Judge, E. Zagadailov, Rengyi Xu, P. Hawkins, V. Beynon, S. Gheuens, E. V. van Beers   +18 more
semanticscholar   +3 more sources

Pyruvate kinase controls signal strength in the insulin secretory pathway

Cell Metabolism, 2020
Pancreatic β-cells couple nutrient metabolism with appropriate insulin secretion. Here, we show that pyruvate kinase (PK), which converts ADP and phosphoenolpyruvate (PEP) into ATP and pyruvate, underlies β-cell sensing of both glycolytic and ...
Sophie L. Lewandowski, Rebecca L. Cardone, Hannah R. Foster, Thuong Ho, E. Potapenko, Chetan Poudel, Halena R. VanDeusen, T. Alves, Xiaojian Zhao, M. Capozzi, Ishrat Jahan, C. Nunemaker, Jonathan E. Campbell, Craig J. Thomas, R. Kibbey, M. Merrins   +15 more
semanticscholar   +3 more sources

HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia.

Cell Metabolism, 2006
Activation of glycolytic genes by HIF-1 is considered critical for metabolic adaptation to hypoxia through increased conversion of glucose to pyruvate and subsequently to lactate.
Jung-whan Kim, Irina Tchernyshyov, G. Semenza, C. Dang   +3 more
semanticscholar   +3 more sources

Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency.

New England Journal of Medicine, 2019
BACKGROUND Pyruvate kinase deficiency is caused by mutations in PKLR and leads to congenital hemolytic anemia. Mitapivat is an oral, small-molecule allosteric activator of pyruvate kinase in red cells.
R. Grace, C. Rose, D. Layton, F. Galactéros, W. Barcellini, D. Morton, E. V. van Beers, H. Yaish, Y. Ravindranath, K. Kuo, S. Sheth, J. Kwiatkowski, A. Barbier, S. Bodie, B. Silver, L. Hua, C. Kung, P. Hawkins, M. Jouvin, C. Bowden, B. Glader   +20 more
semanticscholar   +3 more sources

Cysteine catabolism and the serine biosynthesis pathway support pyruvate production during pyruvate kinase knockdown in pancreatic cancer cells

Cancer & Metabolism, 2019
Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with limited treatment options. Pyruvate kinase, especially the M2 isoform (PKM2), is highly expressed in PDAC cells, but its role in pancreatic cancer remains controversial.
Lei Yu, Shao Thing Teoh, Elliot Ensink, Martin P. Ogrodzinski, Che Yang, Ana I. Vazquez, Sophia Y. Lunt   +6 more
doaj   +2 more sources

Pyruvate Kinase Deficiency [PDF]

Exploration of Host Genetic Factors associated with Malaria, 2020
Pyruvate kinase deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the body's tissues. People with this disorder have a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo ...
T. Qidwai
semanticscholar   +2 more sources

Pyruvate kinase directly generates GTP in glycolysis, supporting growth and contributing to guanosine toxicity [PDF]

mBio
Guanosine triphosphate (GTP) is essential for macromolecular biosynthesis, and its intracellular levels are tightly regulated in bacteria. Loss of the alarmone (p)ppGpp disrupts GTP regulation in Bacillus subtilis, causing cell death in the presence of ...
Fukang She, Kuanqing Liu, Brent W. Anderson, Tippapha Pisithkul, Yanxiu Li, Danny K. Fung, Tyler McCue, William Mulhern, Daniel Amador-Noguez, Jue D. Wang   +9 more
doaj   +2 more sources