All of the following are true regarding iron absorption and homeostasis EXCEPT:

## Iron Absorption and Homeostasis: Mechanism and Regulation ### Correct Answer Analysis **Ferric iron (Fe³⁺) is MORE readily absorbed than ferrous iron (Fe²⁺)** — This statement is FALSE and is the exception. **Key Point:** Ferrous iron (Fe²⁺) is the form preferentially absorbed by the intestinal mucosa. The divalent metal transporter 1 (DMT1) actively transports Fe²⁺ across the apical membrane of enterocytes. Ferric iron (Fe³⁺) must first be reduced to Fe²⁺ by ferrireductase (DCYTB) before absorption can occur. Therefore, Fe²⁺ is the absorbable form, not Fe³⁺. ### Why the Other Statements Are Correct | Statement | Validity | Explanation | |-----------|----------|-------------| | Hepcidin degrades ferroportin | ✓ TRUE | Hepcidin is the iron-regulatory hormone synthesized by hepatocytes. It binds to ferroportin on enterocytes and macrophages, triggering internalization and degradation of the transporter, thereby reducing iron export into blood. | | Iron absorption in duodenum/proximal jejunum via DMT1 | ✓ TRUE | DMT1 (SLC11A2) is the primary transporter for Fe²⁺ absorption. The duodenum and proximal jejunum have the highest concentration of DMT1 and are the major sites of iron absorption. | | Body iron balance via intestinal absorption regulation | ✓ TRUE | The body has no physiologic mechanism to excrete excess iron (no iron-excretory pathway). Iron balance is maintained entirely by regulating intestinal absorption through hepcidin-ferroportin signaling. | ### High-Yield Clinical Pearl **Mnemonic: Fe²⁺ is the ABSORBED form — DMT1 transports the Divalent (2+) cation.** In clinical practice: - Ferrous salts (FeSO₄, FeFumarate) are preferred over ferric salts for oral iron supplementation because Fe²⁺ is directly absorbable. - Vitamin C (ascorbic acid) enhances iron absorption by reducing Fe³⁺ to Fe²⁺ and keeping iron in the acidic microenvironment of the proximal small intestine. - Proton pump inhibitors reduce iron absorption by raising gastric pH, which shifts iron toward the ferric form and reduces DMT1 activity.