GeneID: 375

Description:
The PKLR gene encodes pyruvate kinase, a glycolytic enzyme that catalyzes the transphosphorylation from phosphoenolpyruvate (PEP) to ADP, yielding pyruvate and ATP. It is the last and rate-limiting step of glycolytic pathway. The PKLR gene codes for four isozymes; L is the main form in liver, R is found in red cells, M1 is the main form in muscle, heart and brain, and M2 is found in early foetal tissues. Pyruvate kinase deficiency (PKD) is the most frequent red blood cell enzyme abnormality of the glycolytic pathway and the most common cause of hereditary nonspherocytic haemolytic anaemia. Of particular relevance to sickle cell disease (SCD), a reduction in pyruvate kinase activity leads to accumulation of the upstream enzyme substrates, including 2,3-diphospho-glycerate (2,3-DPG) which decreases oxygen affinity, favoring polymerization of deoxy-HbS. In addition, increased 2,3-DPG concentration decreases intracellular pH in red blood cells which further promotes HbS polymerization. Drug interventions that increase pyruvate kinase activity, thereby lowering 2,3-DPG levels, are explored as therapeutic options to SCD.

Synonyms: PK1 , PKL , RPK , PKRL

Comments:
N/A

Number of entries/variants: 0

1. Eaton WA, Bunn HF, Treating sickle cell disease by targeting HbS polymerization., Blood, 129(20), 2719-2726, 2017 PubMed
2. Xu JZ, Thein SL, The carrier state for sickle cell disease is not completely harmless., Haematologica, 104(6), 1106-1111, 2019 PubMed