After ferrous gluconate is absorbed in the intestine, its core active component—iron ions (Fe²⁺)—undergoes a series of metabolic processes: "form transformation, binding to blood carriers, uptake by target cells, and functional distribution." Among these, the "release of iron ions" and "targeted transport" rely on the synergistic action of specific carrier proteins in the blood, cell surface receptors, and regulatory molecules, ultimately achieving the precise distribution of iron ions to tissues throughout the body to meet physiological needs.

I. Post-Intestinal Absorption: Key Steps of Iron Ion "Form Transformation" and Entry into the Blood

After ferrous gluconate undergoes preliminary processing in intestinal mucosal cells, it must first undergo form transformation before entering the blood:

Iron ions released into the extracellular tissue fluid of mucosal cells via the intestinal transport protein ferroportin (FPN) initially exist in the form of divalent iron (Fe²⁺). However, the oxidizing environment in the blood easily destabilizes Fe²⁺, and the core carrier responsible for iron transport in the blood only recognizes trivalent iron (Fe³⁺). Therefore, "hephaestin" (a membrane-bound iron transport accessory protein) on the basolateral membrane of mucosal cells and "ceruloplasmin" (a copper-containing oxidase) in the blood rapidly oxidize Fe²⁺ to Fe³⁺. This "divalent-to-trivalent" transformation is a prerequisite for iron ions to enter the blood smoothly and participate in subsequent transport. It prevents Fe²⁺ from being oxidized into an inactive form in the blood or causing oxidative stress due to instability.

The transformed Fe³⁺ immediately enters capillaries, integrates into the bloodstream, and initiates the subsequent transport process.

II. Core Transport in the Blood: "Targeted Delivery" Mediated by Transferrin (Tf)

Over 95% of iron ions in the blood are transported by transferrin (Tf), a glycoprotein synthesized by the liver and known as the "exclusive carrier of iron ions" in the blood. The transport process mediated by Tf is highly specific and efficient:

1. Specific Binding and Complex Formation

Tf molecules have two high-affinity Fe³⁺ binding sites, each capable of precisely binding one Fe³⁺ to form a "transferrin-trivalent iron complex (Tf-Fe³⁺)." This binding is strictly pH-dependent: in the neutral environment of blood (pH ≈ 7.4), Tf has an extremely strong binding affinity for Fe³⁺, firmly "capturing" Fe³⁺ and preventing it from remaining free in the blood (free iron ions are cytotoxic and may cause damage such as lipid peroxidation).

2. "Widespread Circulation" with the Bloodstream

The Tf-Fe³⁺ complex circulates with the bloodstream to all tissues and organs throughout the body (e.g., bone marrow, liver, muscles, brain tissue). Its transport direction is not random but regulated by transferrin receptor 1 (TfR1) on the surface of target cells: different tissue cells adjust the expression level of TfR1 on their cell membranes according to their own iron needs—cells with higher iron demand (e.g., erythroid precursor cells in the bone marrow, rapidly proliferating cells) express more TfR1 and thus have a stronger "capture ability" for the Tf-Fe³⁺ complex.

III. Uptake by Target Cells: "Release" of Iron Ions and Reutilization of Carriers

When the Tf-Fe³⁺ complex reaches the surface of target cells, iron ions enter the cells through "receptor-mediated endocytosis," completing the "release" process from the blood into the cells. This process is divided into three steps:

1. Receptor Binding and Initiation of Endocytosis

The Tf-Fe³⁺ complex specifically binds to TfR1 on the surface of target cells, forming a "complex-receptor" conjugate. The cell then invaginates its membrane to form a vesicle (endosome), which encapsulates the conjugate and transports it into the cell interior.

2. Endosome Acidification and Iron Ion Release

The interior of the endosome is rapidly acidified (pH drops to approximately 5.5). The acidic environment significantly reduces the binding affinity between Tf and Fe³⁺, causing Fe³⁺ to dissociate from Tf’s binding sites and be released into the endosome as free Fe³⁺. Meanwhile, "iron reductase" in the endosome reduces Fe³⁺ back to Fe²⁺ (Fe²⁺ can more easily cross the cell membrane into the cytoplasm). Fe²⁺ then enters the cytoplasm from the endosome via intracellular "divalent metal transporters" (e.g., DMT1, homologous to the transporter used in intestinal absorption).

3. Recycling of Carriers and Receptors

After releasing iron ions, Tf (now called "apo-transferrin") remains bound to TfR1. As the endosome fuses with the cell membrane, the apo-transferrin-TfR1 complex is transported back to the cell surface. In the neutral environment of the blood, the binding affinity between apo-transferrin and TfR1 weakens; apo-transferrin dissociates from the receptor and re-enters the bloodstream, waiting to bind Fe³⁺ again. TfR1 remains on the cell membrane to mediate the next round of Tf-Fe³⁺ complex uptake. This recycling mechanism greatly improves the utilization efficiency of Tf and TfR1, reducing the consumption of protein synthesis.

IV. Intracellular Iron Distribution and Regulation of Metabolic Balance

Fe²⁺ entering the cytoplasm is distributed to different "destinations" according to cellular functional needs, while the dynamic balance of iron ions in the blood is maintained through regulatory mechanisms:

1. Functional Distribution

Erythroid precursor cells in the bone marrow use Fe²⁺ to synthesize hemoglobin (the core component of hemoglobin is iron porphyrin, which is responsible for oxygen transport in the blood).

Hepatocytes convert part of Fe²⁺ to Fe³⁺, which binds to "ferritin" (the main intracellular iron storage protein) to form a storage form. When the body has sufficient iron, the liver stores large amounts of iron for future use.

Other tissue cells (e.g., muscle cells, nerve cells) use Fe²⁺ to synthesize heme-containing enzymes such as cytochromes and catalases, which participate in physiological processes such as energy metabolism and antioxidation.

2. Core Regulation of Metabolic Balance: Hepcidin

The concentration of iron ions in the blood is strictly regulated by hepcidin (secreted by the liver). Its target is FPN on the surface of intestinal mucosal cells and macrophages:

When blood iron concentration is too high, hepcidin binds to FPN, promoting FPN degradation. This reduces intestinal iron absorption (lowering the amount of Fe²⁺ entering the blood) and inhibits the release of stored iron from macrophages.

When blood iron concentration is too low (e.g., in iron-deficiency anemia), hepcidin secretion decreases, restoring FPN activity. This increases intestinal iron absorption and iron release from macrophages, thereby raising blood iron concentration back to the normal range.

This regulatory mechanism acts directly on the "source" of iron ions entering the blood, preventing iron excess in the blood (which may cause liver damage and oxidative stress) or iron deficiency (which leads to anemia).

Summary: Core Logic of Ferrous Gluconate Metabolism in the Blood

The metabolism of iron ions from ferrous gluconate in the blood is essentially a process of "precise transport, on-demand distribution, and dynamic balance":

With Tf as the core carrier, targeted delivery of iron ions from the blood to cells is achieved through specific binding to TfR1 on target cells.

Efficient release of iron ions is accomplished via the endosome acidification mechanism, while carriers and receptors are recycled for reuse.

Finally, hepcidin regulates blood iron concentration to maintain it within the physiological range, meeting core physiological functions such as bone marrow hematopoiesis and cellular metabolism while avoiding the toxic risks of free iron ions.

In this process, the "delivery function" of Tf and the "balance function" of hepcidin are the two keys to ensuring the efficient metabolism of ferrous gluconate in the blood.