Pyruvate kinase liver and RBC (PKLR) (PKLR)

Pyruvate kinase liver and RBC (PKLR) is a rate-limiting glycolytic enzyme that catalyzes the conversion of phosphoenolpyruvate to pyruvate, yielding one molecule of ATP (UniProt P30613). The PKLR gene utilizes alternative promoters to produce the PKL isoform, expressed in the liver, and the PKR isoform, expressed in mature erythrocytes (NCBI Gene ID 5313). In red blood cells, which depend entirely on glycolysis for energy, PKR is essential for maintaining cellular metabolism and membrane integrity; mutations in PKLR lead to pyruvate kinase deficiency, the most common cause of chronic non-spherocytic hemolytic anemia (StatPearls, Pyruvate Kinase Deficiency). Therapeutic intervention focuses on small-molecule allosteric activators like Mitapivat, which bind to and stabilize the enzyme, enhancing its activity even in mutant forms (FDA, Pyrukynd Prescribing Information). This approach aims to increase ATP production, reduce the accumulation of upstream metabolites like 2,3-diphosphoglycerate, and improve the lifespan of red blood cells in patients with hemolytic disorders. Beyond hematology, PKLR is also involved in hepatic glucose regulation and is a subject of study in metabolic and infectious diseases like malaria.

Other names

PKLPKRPK1PKRLR-type pyruvate kinaseL-type pyruvate kinasePyruvate kinase 1Pyruvate kinase L/R

Allosteric activation of the pyruvate kinase enzyme to increase its catalytic activity and stability, thereby restoring ATP levels in red blood cells (FDA, Pyrukynd Label).