Pyruvate kinase liver and red blood cell (PKLR)

Pyruvate kinase isozymes R/L (PKLR) are essential glycolytic enzymes encoded by the PKLR gene, primarily expressed in the liver (L-type) and red blood cells (R-type) [1, 16]. They catalyze the final, rate-limiting step of glycolysis, converting phosphoenolpyruvate (PEP) to pyruvate while generating ATP [5, 15]. In red blood cells, which lack mitochondria, PKLR is the sole source of ATP, making it critical for maintaining membrane integrity and cellular lifespan [2, 23]. Mutations in the PKLR gene lead to pyruvate kinase deficiency, a rare genetic disorder characterized by chronic hemolytic anemia due to ATP depletion and subsequent premature destruction of erythrocytes [4, 17]. Therapeutic intervention focuses on allosteric activation of the enzyme to restore glycolytic flux and ATP production [13]. Drugs like mitapivat bind to the enzyme to stabilize its active conformation, thereby improving hemoglobin levels and reducing the need for blood transfusions in patients with hemolytic anemias [6, 9, 22].

Other names

PKLPKRPK1Pyruvate kinase 1Pyruvate kinase isozymes L/RL-PKR-PK

Allosteric activator that stabilizes the active tetrameric R-state of the enzyme, increasing catalytic activity and affinity for phosphoenolpyruvate to restore ATP levels and reduce 2,3-DPG accumulation.