Pyruvate kinase red blood cell isozyme (PK-R)

Pyruvate kinase red blood cell isozyme (PK-R) is a tissue-specific form of pyruvate kinase uniquely expressed in erythrocytes, encoded by the PKLR gene. It catalyzes the final, irreversible step of glycolysis—conversion of phosphoenolpyruvate (PEP) to pyruvate with concomitant production of ATP, which is critical for energy homeostasis in red blood cells that lack mitochondria. PK-R is allosterically activated by fructose 1,6-bisphosphate and plays a central role in maintaining red cell viability. Deficiency of PK-R caused by mutations in the PKLR gene is the most common glycolytic enzyme defect leading to hereditary nonspherocytic hemolytic anemia, due to ATP depletion and subsequent compromise of erythrocyte integrity[1][3][4][5]. Therapeutic strategies such as allosteric activation (e.g., with Mitapivat/AG-348) aim to restore enzyme function and alleviate disease symptoms in affected individuals.

Other names

Pyruvate kinase RErythrocyte pyruvate kinasePKRRed cell pyruvate kinasePyruvate kinase LR gene product (PKLR)

Allosteric activation/restoration of enzyme function by small molecules (e.g., Mitapivat increases enzymatic activity of PK-R, thereby boosting ATP synthesis in defective red blood cells[4])