The complex journey of iron absorption
Iron is a vital mineral required for the synthesis of hemoglobin, the protein in red blood cells that transports oxygen throughout the body. However, the process of absorbing iron from food is tightly regulated to prevent both deficiency and dangerous iron overload. The primary site of absorption is the duodenum, the first part of the small intestine, and it involves a cast of specialized enzymes and transport proteins that handle two different forms of dietary iron: heme and non-heme iron.
The key enzymes and proteins in iron absorption
Iron absorption is not the work of a single enzyme but a coordinated effort involving several molecular players, each with a specific function in processing either heme or non-heme iron.
Non-Heme Iron Absorption
Non-heme iron, found primarily in plant-based foods, is less bioavailable and must undergo a transformation before it can be absorbed by intestinal cells (enterocytes).
- Duodenal Cytochrome B (DcytB): This enzyme, located on the brush border membrane of the enterocytes, is crucial for the first step. Most non-heme iron in food is in the oxidized ferric state ($Fe^{3+}$), which is not easily absorbed. DcytB acts as a ferrireductase, reducing ferric iron to its more absorbable ferrous state ($Fe^{2+}$). This process is highly dependent on vitamin C, which helps maintain the iron in a soluble, reduced form.
- Divalent Metal Transporter 1 (DMT1): Following the reduction by DcytB, the ferrous iron ($Fe^{2+}$) is transported from the intestinal lumen into the enterocyte via DMT1. The expression of DMT1 is upregulated when the body's iron stores are low to increase absorption.
Heme Iron Absorption
Heme iron, found exclusively in animal products like red meat, fish, and poultry, is more readily absorbed than non-heme iron.
- Heme Carrier Protein 1 (HCP1): Although once believed to be the primary transporter for heme, HCP1's role is now debated, with some evidence suggesting it's mainly a folate transporter. Regardless, the heme molecule, with its bound iron, is absorbed directly and intact into the enterocyte by a mechanism that is less well-understood but appears to be more efficient.
- Heme Oxygenase (HO): Once inside the enterocyte, the heme molecule is catabolized by heme oxygenase, releasing the iron ($Fe^{2+}$) from the porphyrin ring. This released iron then joins the same pathway as non-heme iron.
Iron Export from Enterocytes
After entering the enterocyte, iron can be stored bound to ferritin or exported into the bloodstream, depending on the body's needs.
- Ferroportin (FPN1): Ferroportin is the sole known iron exporter in mammals. This protein transports ferrous iron ($Fe^{2+}$) across the basolateral membrane of the enterocyte into the interstitial fluid and eventually the blood. The activity of ferroportin is the primary point of regulation for systemic iron levels, controlled by the hormone hepcidin.
- Hephaestin (HEPH): This copper-containing enzyme is located on the basolateral membrane of the enterocyte. Its function is to re-oxidize the ferrous iron ($Fe^{2+}$) exported by ferroportin back into the ferric state ($Fe^{3+}$). This oxidation is necessary for iron to bind to its transport protein in the blood, transferrin.
The impact of a nutrition diet on iron absorption
The foods you eat play a massive role in how effectively your body can absorb iron. Certain nutrients enhance absorption, while others can significantly inhibit it.
Enhancers of Iron Absorption
- Vitamin C (Ascorbic Acid): As mentioned, vitamin C is a powerful enhancer, especially for non-heme iron. It helps reduce ferric iron to the more absorbable ferrous form and forms a soluble chelate in the stomach, which persists through the small intestine.
- Meat, Fish, and Poultry: These foods contain heme iron, which is highly bioavailable. Consuming them alongside non-heme iron sources also appears to boost the absorption of the non-heme iron, though the exact mechanism is not fully understood.
Inhibitors of Iron Absorption
- Phytates: These compounds are found in whole grains, cereals, nuts, and legumes and can significantly inhibit the absorption of non-heme iron by binding to it.
- Polyphenols: Found in coffee, tea, and some vegetables and fruits, polyphenols form complexes with iron that reduce its absorption. It is recommended to have tea or coffee between meals rather than with them.
- Calcium: High intakes of calcium, from dairy or supplements, can inhibit the absorption of both heme and non-heme iron. It's best to consume calcium-rich foods or supplements at a different time of day than your main iron-rich meal.
Tips for Optimizing Iron Absorption
- Combine food sources: Add vitamin C-rich vegetables like bell peppers or tomatoes to a meal with non-heme iron sources like lentils or spinach. A squeeze of lemon juice can also help.
- Time your consumption: If you take calcium supplements or consume a lot of dairy, separate these from your iron-rich meals. The same goes for coffee and tea.
- Cook with cast iron: Using cast iron cookware can naturally increase the iron content of your food.
- Address deficiencies: Iron deficiency itself prompts the body to increase its absorption mechanisms, but it's important to correct the underlying cause through dietary changes and, if necessary, supplementation under medical supervision.
Comparison of Heme and Non-Heme Iron Absorption
| Feature | Heme Iron | Non-Heme Iron |
|---|---|---|
| Source | Animal products (meat, fish, poultry) | Plant-based foods (grains, legumes, nuts, vegetables) |
| Bioavailability | Highly bioavailable; up to 40% absorbed. | Poorly bioavailable; absorption varies from 2-20%. |
| Absorption Mechanism | Absorbed intact as a heme molecule, then cleaved by heme oxygenase inside enterocytes. | Reduced by DcytB to ferrous form, then transported by DMT1 into enterocytes. |
| Dietary Inhibitors | Less affected by dietary inhibitors like phytates and polyphenols. | Highly sensitive to inhibitors like phytates, polyphenols, and calcium. |
| Dietary Enhancers | Not significantly influenced by enhancers. | Highly responsive to enhancers like vitamin C and the 'meat factor'. |
Conclusion: orchestrating the complex process
Instead of asking what enzyme absorbs iron, a more accurate question is, 'what enzymes and proteins are involved in the intricate process of iron absorption?' The process relies on a sequence of enzymatic reactions and transport proteins that work to process and transport dietary iron into the body. This includes DcytB for reducing non-heme iron and heme oxygenase for liberating iron from heme, followed by transport via DMT1 and export through ferroportin and hephaestin. A balanced nutrition diet rich in enhancers like vitamin C and heme iron sources, while strategically managing intake of inhibitors, is essential for optimizing this complex and vital metabolic pathway.
Visit the NCBI website to learn more about the biochemical details of iron absorption.
