In pyruvate kinase deficiency, the final step of glycolysis, which converts phosphoenolpyruvate (PEP) to pyruvate, is impaired. Consequently, the glycolytic intermediates upstream of this step accumulate because they cannot be efficiently converted into pyruvate.
One key glycolytic intermediate that builds up in pyruvate kinase deficiency is 2,3-bisphosphoglycerate (2,3-BPG). This compound plays a vital role in regulating the oxygen-binding affinity of hemoglobin. Normally, 2,3-BPG binds to hemoglobin and stabilizes its low-affinity state, facilitating the release of oxygen to tissues. However, when 2,3-BPG levels are elevated due to pyruvate kinase deficiency, it can lead to an increased affinity of hemoglobin for oxygen, impairing its release to tissues. This can result in lower tissue oxygen saturation despite normal or high levels of oxygen in the blood.
Additionally, other glycolytic intermediates such as glucose-6-phosphate and fructose-1,6-bisphosphate may also accumulate in pyruvate kinase deficiency. These intermediates can have various metabolic consequences, including diversion into alternative pathways such as the pentose phosphate pathway or the formation of advanced glycation end products, which can contribute to cellular damage and oxidative stress.
In summary, in pyruvate kinase deficiency, the accumulation of glycolytic intermediates such as 2,3-BPG can impair the release of oxygen from hemoglobin to tissues, leading to lower tissue oxygen saturation. This contributes to the anemia and tissue hypoxia observed in individuals with this disorder.