Divalent Manganese: The Primary Absorbed Form
The journey of manganese from food to cells begins in the small intestine, where it is primarily absorbed as the divalent manganese ion ($Mn^{2+}$). This uptake mechanism is shared with other divalent cations, most notably iron ($Fe^{2+}$), which leads to significant competition between these two essential minerals. The rate of absorption is typically low in adults, averaging only 1-5% of ingested manganese, but this figure can vary depending on a range of factors. The primary active transporter responsible for this process is the Divalent Metal Transporter 1 (DMT1).
The Role of Divalent Metal Transporter 1 (DMT1)
DMT1 is an integral membrane protein found on the surface of intestinal cells. Its function is to actively transport certain metal ions from the gut lumen into the cell. Because DMT1 also transports iron, the body's iron status has a major impact on manganese absorption. In cases of iron deficiency, DMT1 expression is upregulated to increase iron uptake, but this also inadvertently increases manganese absorption. Conversely, high iron stores can inhibit manganese uptake. This competitive relationship between iron and manganese via DMT1 is a critical aspect of mineral homeostasis, helping to regulate overall levels of both minerals.
Passive Diffusion: A Secondary Pathway
In addition to the regulated, active transport via DMT1, manganese can also be absorbed through passive diffusion. This non-specific pathway becomes more significant when dietary intake of manganese is very high, overwhelming the capacity of the DMT1 system. While essential for coping with high intake, passive diffusion can contribute to accumulation and toxicity if exposure is chronic and excessive.
Transport After Absorption: From Divalent to Trivalent
Once absorbed into the bloodstream, manganese undergoes a change in its chemical form to facilitate transport and distribution throughout the body. Initially, it travels from the gut to the liver as $Mn^{2+}$, bound to plasma proteins like albumin. The liver, which is the body's central regulator of manganese, then plays a crucial role in modifying and distributing it. The liver and plasma ceruloplasmin oxidize a portion of the absorbed $Mn^{2+}$ into its trivalent form, $Mn^{3+}$. This $Mn^{3+}$ then binds to transferrin (Tf), the same protein responsible for transporting iron ($Fe^{3+}$). This further underscores the metabolic link between iron and manganese. Transferrin-bound manganese is then distributed to various extrahepatic tissues, including the brain, where it can be taken up via transferrin receptors.
Regulation and Excretion
The body maintains manganese homeostasis through a delicate balance of absorption and excretion. The liver is the primary organ responsible for this regulation, as it is the main source of manganese elimination. More than 90% of absorbed manganese is excreted via bile into the feces, making this the most important pathway for eliminating excess manganese and preventing toxicity. Since the liver is so central to excretion, individuals with liver diseases are at a heightened risk for manganese accumulation and potential neurotoxicity. Neonates and infants have a less mature biliary excretion system, making them more vulnerable to manganese accumulation during early development.
Comparative Table: Absorption Pathways of Manganese
| Feature | Active Transport (DMT1) | Passive Diffusion |
|---|---|---|
| Mechanism | Regulated, protein-mediated transport | Non-specific movement down a concentration gradient |
| Primary Form | Divalent ion ($Mn^{2+}$) | Primarily divalent ion ($Mn^{2+}$) |
| Competition | High competition with other divalent metals, especially iron | Less affected by competition from other minerals |
| Dietary Context | Operates efficiently under normal physiological conditions | Becomes significant when dietary intake is very high |
| Energy Requirement | Requires energy (ATP) | Does not require metabolic energy |
| Efficiency | Highly efficient but has limited capacity | Less efficient but becomes dominant at high concentrations |
Conclusion: A Multi-faceted Absorption Process
In conclusion, manganese absorption is a sophisticated process centered on the divalent ($Mn^{2+}$) form. It relies on both an active transport system, regulated by the Divalent Metal Transporter 1 (DMT1), and passive diffusion for handling different levels of dietary intake. The interaction with iron for the shared DMT1 transporter is a key factor influencing bioavailability. Following intestinal absorption, the liver tightly controls manganese distribution and excretion, with the mineral often being converted to a trivalent ($Mn^{3+}$) form and bound to transferrin for systemic transport. This multi-layered regulatory system ensures that the body receives and processes this essential trace mineral efficiently while protecting against toxic overload.
