RBC, heal thyself: PK activators in SCD Comment

In this issue of Blood, Xu et al(1) open the hood of the sickle hemoglobin (HbS)-containing red blood cells (RBCs) and cleverly soup up the carburetor; that is, they exploit endogenous metabolic pathways to improve RBC health in sickle cell disease (SCD) through activation of a distal enzyme in the glycolytic pathway, pyruvate kinase2 (PK; see figure). The goal is to increase the oxygen affinity of HbS by decreasing the concentration of the allosteric effector 2,3-diphosphoglycerate (2,3-DPG).

Automated summary

Researchers cleverly improve red blood cell health in sickle cell disease patients by activating the enzyme PK in the glycolytic pathway, which reduces the concentration of 2,3-DPG and increases the oxygen affinity of HbS.