Overview
This lecture reviews how vitamin C enables the absorption of non-heme iron by enterocytes and connects this process to red blood cell production (erythropoiesis) and antioxidant (redox) capacity of human erythrocytes.
Nutrient Absorption by Enterocytes
- Enterocytes absorb nutrients such as ions, glucose, glutamine, and vitamins from the gut and transport them into the bloodstream.
- Non-heme iron uptake by enterocytes is vitamin C-dependent, requiring ascorbic acid to reduce ferric (Fe³⁺) to ferrous (Fe²⁺) iron.
- The acidic stomach environment and ascorbic acid form a soluble iron chelate, facilitating absorption in the duodenum.
Iron Absorption and Transport Mechanisms
- Heme iron is absorbed intact by enterocytes and released as Fe²⁺ after enzymatic degradation.
- Non-heme iron absorption involves duodenal cytochrome b (Dcytb) reducing Fe³⁺, followed by DMT1-mediated H⁺/Fe²⁺ cotransport.
- Basolateral iron efflux requires ferroportin-1 and hephaestin, with transferrin distributing iron systemically.
Metabolic Roles and Regulation
- Enterocytes use glutamine and glucose for energy, producing lactate and H⁺, which activate hypoxia-inducible factor 1-alpha (Hif-1α).
- Hif-1α regulates genes involved in pH balance, glycolysis, and iron transport, essential for optimal erythropoiesis.
- pH gradients in the gut influence DMT1 abundance and iron uptake efficiency.
Erythropoiesis and Iron Homeostasis
- Erythropoiesis requires folates, vitamin B12, Fe²⁺, and is regulated by erythropoietin (EPO), testosterone, and hepcidin.
- Hepcidin controls iron efflux by modulating ferroportin, preventing iron overload and supporting balanced erythropoiesis.
- Iron for hemoglobin biosynthesis in erythroid precursors is supplied mainly via transferrin-bound Fe³⁺.
Redox Capacity in Erythrocytes
- Inside red blood cells, ascorbic acid (vitamin C) is regenerated from dehydroascorbic acid (DHA) by glutathione (GSH) and NADH.
- This recycling protects cell membranes from lipid peroxidation, maintaining cell integrity and minimizing hemolysis.
Drug Effects on Iron Metabolism
- Cationic amphiphilic drugs (CADs) like desipramine can disrupt endosomal/lysosomal pH, impeding iron release and heme synthesis in erythropoiesis.
- Such drugs should be used cautiously, especially during pregnancy, due to possible negative effects on red blood cell production.
Key Terms & Definitions
- Enterocyte — Intestinal cell responsible for nutrient absorption.
- Non-heme iron — Form of dietary iron not bound to heme proteins.
- Ascorbic acid (Vitamin C) — Reducing agent that enables non-heme iron absorption.
- Dcytb — Duodenal cytochrome b, a ferric reductase enzyme.
- DMT1 — Divalent metal transporter 1, transports Fe²⁺ into cells.
- Ferroportin-1 — Basolateral iron exporter in enterocytes.
- Transferrin — Plasma protein binding and delivering iron throughout the body.
- Erythropoiesis — Process of red blood cell production.
- Hepcidin — Liver hormone regulating systemic iron balance.
- Glutathione (GSH) — Tripeptide involved in antioxidant defense and vitamin C recycling.
Action Items / Next Steps
- Review mechanisms of dietary iron absorption, especially the role of vitamin C and DMT1.
- Study the regulation of erythropoiesis and the effects of drugs like desipramine on iron metabolism.
- Understand the interplay between antioxidant systems (vitamin C, GSH) and erythrocyte health.