Pyruvate kinase liver and RBC (PKR)

Pyruvate kinase, erythrocyte isoform (PKR) is a critical glycolytic enzyme that catalyzes the final step of glycolysis, converting phosphoenolpyruvate and ADP into pyruvate and ATP [1]. Because mature red blood cells lack mitochondria, they depend entirely on PKR-mediated glycolysis for ATP production to maintain cellular membrane integrity and ion homeostasis [2]. Deficiencies in this enzyme, caused by mutations in the PKLR gene, result in chronic non-spherocytic hemolytic anemia due to energy failure within the erythrocyte [3]. Therapeutic intervention focuses on allosteric activators, such as mitapivat, which bind to the PKR tetramer and increase its catalytic activity [4]. These drugs are designed to restore ATP levels and reduce the accumulation of 2,3-diphosphoglycerate, thereby improving red cell survival and oxygen affinity [5]. Beyond pyruvate kinase deficiency, PKR activators are being evaluated for their potential to treat other hematologic disorders like sickle cell disease and beta-thalassemia [6].

Other names

Pyruvate kinase L/RPKLRR-type pyruvate kinaseErythrocyte pyruvate kinasePK1

Small-molecule allosteric activation of the PKR tetramer to increase glycolytic flux and ATP production while reducing 2,3-diphosphoglycerate (2,3-DPG) levels.