Biochemistry: Iron Absorption

Introduction

• Essential Role: Iron is vital for DNA synthesis, electron transport, and oxygen transport.
• Regulation: Controlled primarily by absorption, not excretion.
• Body Iron Storage:
  • Erythrocytes as hemoglobin (2g in men, 1.5g in women).
  • Storage compounds: ferritin, hemosiderin.
  • Muscle cells as myoglobin.
  • Bound to proteins and non-heme enzymes.
• Labile Pool: Reactive pool forming reactive oxygen species, involved with iron overload treatment through chelators.

Fundamentals

• Types of Iron:
  • Heme Iron: From animal sources; easily absorbed (15%-35%).
  • Non-heme Iron: From plants and fortified foods; less absorbable.
• Dietary Iron Challenges:
  • Low intake leads to anemia.
  • Insoluble iron oxides form upon oxygen exposure, reducing absorption.
• Oxidation and Reduction:
  • Enterocytes reduce ferric (Fe3+) to ferrous (Fe2+) for absorption.
  • Balance needed to avoid iron deficiency and overload.

Cellular Level

• Absorption Site: Duodenum and proximal jejunum.
• Physiological Process:
  • Ferric to Ferrous Conversion: Facilitated by duodenal cytochrome B (Dcytb) in acidic environment.
  • Transport: DMT1 protein transports iron into cells.
• Inhibitors and Enhancers:
  • Inhibitors: Phytate, polyphenols, calcium, animal/plant proteins, oxalic acid.
  • Enhancers: Ascorbic acid (Vitamin C).

Molecular Level

• Iron Storage and Transport:
  • Stored as ferritin or transported by ferroportin.
  • Ferritin oxidizes ferrous to ferric for storage.
• Hepcidin Regulation:
  • High hepcidin levels inhibit ferroportin, shunting iron to ferritin.
  • Low hepcidin allows iron release and transport.
• Transferrin Role:
  • Chelates iron for transport, prevents reactive species formation, and facilitates cell transport.

Clinical Significance

• Iron Absorption Disorders:
  • Conditions affecting duodenal mucosa reduce absorption.
  • Includes diseases like celiac, Crohn’s, and duodenal cancer.
• Types of Anemia:
  • Anemia of Chronic Disease: Elevated ferritin but low total iron due to inflammatory cytokines.
  • Iron-deficiency Anemia: Due to hemorrhage, low dietary iron, or absorption issues; common in menstruating women, pregnant, and breastfeeding women.