BIOCHEMICAL FOUNDATIONS OF IRON METABOLISM AND ERYTHROCYTE METABOLISM IN ANEMIAS

Anemic syndromes represent a diverse group of hematological and systemic disorders unified by a reduction in circulating functional hemoglobin mass and impaired tissue oxygenation, yet underpinned by distinct molecular disruptions in systemic iron kinetics and intra-erythrocytic bioenergetics. Because mature mammalian erythrocytes lack nuclei, mitochondria, and ribosomes, their structural integrity, deformability, and oxygen-carrying capacity rely exclusively on anaerobic Embden-Meyerhof glycolysis, the Rapoport-Luebering bisphosphoglycerate shunt, and the hexose monophosphate oxidative pathway. However, routine clinical evaluations of anemias focus predominantly on peripheral blood counts and basic ferro-kinetic markers, largely neglecting the profound metabolic coupling between systemic iron homeostasis and intracellular erythrocyte energetics. This comprehensive clinical-biochemical study investigates the molecular interplay between systemic iron metabolism indicators and key parameters of intra-erythrocytic carbohydrate, energy, and redox metabolism across patients diagnosed with iron deficiency anemia and anemia of chronic inflammation. A cohort of patients with clinically confirmed anemic syndromes was systematically evaluated alongside an age- and sex-matched healthy control group. Biochemical profiling encompassed the quantification of serum iron, transferrin saturation, ferritin, soluble transferrin receptors, and hepcidin-twenty-five, coupled with the spectrophotometric and chromatographic assessment of intra-erythrocytic adenosine triphosphate, two,three-bisphosphoglycerate, glucose-six-phosphate dehydrogenase activity, pyruvate kinase activity, reduced glutathione, methemoglobin, and membrane malondialdehyde levels. The findings demonstrate that while iron deficiency anemia and anemia of chronic inflammation exhibit divergent hepcidin and ferritin profiles, both conditions induce a severe depletion of intra-erythrocytic adenosine triphosphate and reduced glutathione, accompanied by a compensatory surge in two,three-bisphosphoglycerate, elevated methemoglobin formation, and accelerated membrane lipid peroxidation. Furthermore, transferrin saturation and blood hemoglobin correlated positively with erythrocyte adenosine triphosphate and glucose-six-phosphate dehydrogenase activity, and inversely with intra-erythrocytic two,three-bisphosphoglycerate and membrane malondialdehyde concentrations. The study concludes that simultaneous evaluation of systemic iron kinetics and intra-erythrocytic metabolic biomarkers provides a comprehensive pathophysiological framework for differentiating anemic syndromes, assessing erythrocyte functional viability, and optimizing combined metabolic and ferro-therapeutic interventions.