Activation of pyruvate kinase as therapeutic option for rare hemolytic anemias: Shedding new light on an old enzyme

Myrthe J van Dijk, Jonathan R A de Wilde, Marije Bartels, Kevin H M Kuo, Andreas Glenthøj, Minke A E Rab, Eduard J van Beers, Richard van Wijk*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Abstract

Novel developments in therapies for various hereditary hemolytic anemias reflect the pivotal role of pyruvate kinase (PK), a key enzyme of glycolysis, in red blood cell (RBC) health. Without PK catalyzing one of the final steps of the Embden-Meyerhof pathway, there is no net yield of adenosine triphosphate (ATP) during glycolysis, the sole source of energy production required for proper RBC function and survival. In hereditary hemolytic anemias, RBC health is compromised and therefore lifespan is shortened. Although our knowledge on glycolysis in general and PK function in particular is solid, recent advances in genetic, molecular, biochemical, and metabolic aspects of hereditary anemias have improved our understanding of these diseases. These advances provide a rationale for targeting PK as therapeutic option in hereditary hemolytic anemias other than PK deficiency. This review summarizes the knowledge, rationale, (pre)clinical trials, and future advances of PK activators for this important group of rare diseases.

Original languageEnglish
Article number101103
JournalBlood Reviews
Volume61
Early online date12 Jun 2023
DOIs
Publication statusPublished - Sept 2023

Keywords

  • Glycolysis
  • Hemolytic anemia
  • Pyruvate kinase
  • Treatment

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