HTF Human

Holo Transferrin is composed of a single polypeptide chain with a molecular mass of approximately 76-81 kDa . It has two homologous iron-binding domains, the N-terminal and C-terminal, each capable of binding one ferric ion (Fe³⁺) in the presence of an anion, typically carbonate . The binding of iron to transferrin is highly specific and involves coordination with a histidine nitrogen, an aspartic acid carboxylate oxygen, and two tyrosine phenolate oxygens .

The primary function of Holo Transferrin is to transport iron from sites of absorption and storage to sites of utilization, such as the bone marrow, liver, and spleen . Iron is essential for various biological processes, including oxygen transport, DNA synthesis, and electron transport. By binding and transporting iron, Holo Transferrin helps maintain iron homeostasis and prevents iron-mediated oxidative damage.

The binding of ferric iron to transferrin is a highly regulated process. Ferric iron couples to transferrin only in the presence of an anion that serves as a bridging ligand between the metal and the protein, excluding water from the coordination sites . This binding is characterized by a high association constant, approximately 10²² M⁻¹ . The release of iron from transferrin involves the protonation of the carbonate anion, which loosens the metal-protein bond .

Under normal physiological conditions, approximately one-third of the iron-binding sites on transferrin are occupied . This ensures that non-transferrin-bound iron in the circulation is virtually nonexistent, preventing potential toxicity. The total iron-binding capacity (TIBC) of plasma is a measure of the maximum amount of iron that can be bound by transferrin .

Holo Transferrin plays a vital role in iron metabolism and distribution. It is involved in the receptor-mediated endocytosis of iron-loaded transferrin by cells . Receptors on the plasma membrane bind Holo Transferrin with high affinity, facilitating the uptake of iron into cells. The C-terminal domain of transferrin mediates receptor binding, with diferric transferrin (iron-bound at both sites) binding with higher affinity than monoferric transferrin (iron-bound at one site) or apotransferrin (iron-free) .

Once inside the cell, iron is released from transferrin in the acidic environment of endosomes and is utilized for various cellular processes . The remaining transferrin, now in its iron-free form (apotransferrin), is recycled back to the cell surface and released into the circulation to bind more iron .

The measurement of Holo Transferrin levels in the blood is an important diagnostic tool for assessing iron status and diagnosing iron-related disorders. Elevated levels of Holo Transferrin can indicate iron overload conditions, such as hemochromatosis, while decreased levels may suggest iron deficiency anemia . Additionally, the total iron-binding capacity (TIBC) and transferrin saturation are commonly used parameters in clinical practice to evaluate iron metabolism .