Targeting Pyruvate Kinase: Novel Therapeutic Strategies in Metabolic and Blood Disorders

Year 2025, Volume: 45 Issue: 4, 374 - 387, 01.12.2025

Thoppalada Yunus Pasha , Manojmouli Chandramouli

https://doi.org/10.52794/hujpharm.1691229

Abstract

Pyruvate kinase (PK) is a critical enzyme in the final step of glycolysis, catalyzing the conversion of phosphoenolpyruvate to pyruvate, while generating ATP in the process. There are several isoforms of PK, including PKM1, PKM2, PKL, and PKR, expressed in a tissue-specific manner. PKM1 is predominantly found in tissues with high-energy demands, such as muscle, while PKM2 is present in proliferating cells, including tumor cells. PKL is mainly expressed in the liver, and PKR is primarily found in red blood cells. Beyond its role in energy metabolism, PK dysfunction is implicated in various metabolic and hematologic disorders. Defects in PK, such as pyruvate kinase deficiency, lead to hemolytic anemia and other blood disorders. Current drug discovery efforts, including the development of Mitapivat, aim to address PK deficiencies and improve red blood cell function. Mitapivat, a potent activator of PK, has shown promise in clinical trials for treating PK deficiency. The future of PK-targeted therapies looks bright, with ongoing research focusing on the development of selective PK activators and inhibitors to treat metabolic diseases, cancer, and hematologic disorders. These therapeutic strategies offer the potential to enhance cellular metabolism and improve patient outcomes.

Keywords

Pyruvate Kinase , Cancer , Hemolytic Anemia , Tetrameric

Thanks

I would like to express my sincere gratitude to my Ph. D guide Dr T Yunus Pasha to contributed to this review. I extend my deepest appreciation to our institution “Faculty of Pharmacy-Sri Adichunchanagiri College of Pharmacy” for providing the necessary resources and support.

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