Chapter 42: The Biochemistry of Erythrocytes and Other Blood Cells

Red blood cells depend exclusively on glycolytic metabolism to generate ATP, while simultaneously producing 2,3-bisphosphoglycerate to modulate hemoglobin oxygen affinity and ensure efficient oxygen delivery to tissues. The pentose phosphate pathway supplies NADPH necessary for maintaining cellular redox balance and preventing oxidative damage to membrane lipids and proteins. Heme synthesis, initiated from glycine and succinyl-CoA substrates, requires precise iron homeostasis through transferrin-mediated transport and ferritin storage; disruptions in this system result in iron-deficiency anemia or lead poisoning-related heme synthesis impairment. The erythrocyte membrane's mechanical resilience depends on a spectrin-anchored cytoskeletal lattice linked through ankyrin and band proteins; structural defects in these components cause hereditary spherocytosis and hemolytic anemia. Hemoglobinopathies including sickle cell disease and thalassemias arise from mutations altering globin synthesis or function, while understanding hemoglobin F regulation offers therapeutic pathways for disease amelioration. Glucose-6-phosphate dehydrogenase deficiency exemplifies how enzyme defects increase hemolysis susceptibility under oxidative stress despite conferring malaria resistance. The chapter discusses hematopoiesis, the orchestrated generation of all blood cell lineages from bone marrow stem cells through cytokine signaling via JAK-STAT pathways, with dysregulation underlying leukemias and immunodeficiencies. Heme catabolism produces bilirubin through sequential enzymatic degradation, connecting erythrocyte lifespan to jaundice pathogenesis and biliary disease. Clinical presentations of β-thalassemia, hereditary spherocytosis, and acute hemolytic crises illustrate how molecular defects propagate systemic pathological consequences. This chapter synthesizes structural biology, intermediate metabolism, genetic regulation, and clinical disease manifestations to provide comprehensive insight into blood cell biochemistry across physiological and pathological states.