Iron binding proteins transferrin

This receptor-mediated endocytotic pathway has been especially well studied in the uptake of iron from blood plasma. Iron, because of its very low-solubility product (< 1(T17 at pH 7.4), is transported in plasma bound to the iron-binding protein transferrin. Two Fe3+ ions bind to each transferrin molecule. Entry into... 

In the extracellular fluids of mammals, the iron-binding protein transferrin is usually only 30% saturated, so that it has 70% of its metal-binding capacity free. If Al3+ could get... 

In the extracellular fluids of mammals, the iron-binding protein transferrin is usually only 30% saturated, so that it has 70% of its metal-binding capacity free. If AI + could get into the circulation, it could certainly occupy those binding sites. The stability constants for the two binding sites on transferrin are similar, log Ka of 12.9 and 12.3 (Martin, 1994), substantially lower than for iron. 

Among the common macromolecules that vertebrate cells internalize by receptor-mediated endocytosis are cholesterol-containing particles called low-density lipoprotein (LDL) the iron-binding protein transferrin many protein hormones (e.g., insulin) and certain glycoproteins. Receptor-mediated endocytosis of such ligands generally occurs via clathrin/AP2-... 

There are 50-70 mmol (3-4 g) of iron in the body. Three-quarters are present as the molecular complex with haem. Most of the remainder is in tissue stores bound to the iron storage proteins, ferritin and haemosiderin. Less than one per cent of total body iron is in the plasma, where it is associated with the iron-binding protein, transferrin. Body iron is efficiently reutilized. Dietary intake is about 0.35 mmol (20 mg) per day. The factors which regulate intestinal absorption of iron are poorly understood (Fig. 2). 

FET3 gene product of S. cerevisiae is a multicopper oxidase and plays a key role in iron metabolism of this eukaryote has underpinned the function of ceruloplasmin in vertebrate iron transport. By virtue of its ferroxidase activity, ceruloplasmin converts Fe(II) into Fe(III), which binds to the iron-binding protein transferrin. Ceruloplasmin is critical for iron egress from some cell types. The transport system responsible for iron release into plasma has not been identified. ... 

Iron-binding proteins (transferrin, hae-mosideroin and ferritin) (Halliwell and Gutteridge,... 

Figure 50-4. Absorption of iron. is converted to Fe + by ferric reductase, and Fe " is transported into the enterocyte by the apicai membrane iron transporter DMTl. Fieme is transported into the enterocyte by a separate heme transporter (HT), and heme oxidase (FiO) reieases Fe from the heme. Some of the intraceiiuiar Fe + is converted to Fe + and bound by ferritin. The remainder binds to the basoiaterai Fe + transporter (FP) and is transported into the biood-stream, aided by hephaestin (FiP). in piasma, Fe + is bound to the iron transport protein transferrin (TF). (Reproduced, with permission, from Ganong WF Review of Medical Physiology, 21 st ed. McGraw-Hill, 2003.)...

The determination of the structure of the iron transporter, ferric-binding, protein (hFBP)t from Haemophilus influenzae (Bruns et ah, 1997) at 0.16 nm resolution shows that it is a member of the transferrin superfamily, which includes both the transferrins and a number of periplasmic binding proteins (PBP). The PBPs transport a wide variety of nutrients, including sugars, amino acids and ions, across the periplasm from the outer to the inner (plasma) membrane in bacteria (see Chapter 3). Iron binding by transferrins (see below) requires concomitant binding of a carbonate anion, which is located at the N-terminus of a helix. This corresponds to the site at which the anions are specifically bound in the bacterial periplasmic sulfate- and... 

Transferrin iron uptake via receptor-mediated endocytosis has clearly appeared fairly late in evolution, when we consider that the bilobal iron-binding protein is found only as far back as insects . As we have seen in the preceding chapters, iron-uptake mechanisms involving the synthesis of more or less specific siderophores have evolved together with strategies implying the solubilization of insoluble ferric iron by the combined effects of pH and reduction, and even the development of receptor proteins capable of taking up transferrin-, lactoferrin- or haem-bound iron from specific hosts. 

For most living bacteria (lactobacilli being the only notable exception [154]) iron is an essential nutrient. Iron is not readily available under normal conditions, although it is the fourth most abundant metal on earth. In the environment it is mainly found as a component of insoluble hydroxides in biological systems it is chelated by high-affinity iron binding proteins (e.g. transferrins,... 

In addition to the amino acid side chains mentioned above, a number of other low molecular weight ligands are found in metalloproteins. These include cyanide and carbon monoxide, which we will describe later in this chapter. Here we consider carbonate and phosphate anions in the context of the super family of iron-binding proteins, the transferrins. 

Another example is uptake of the iron-containing protein, transferrin, which circulates in the blood. It binds to its receptor to form a complex that enters the cell via endocytosis. The iron is then released from the endosome for use in the cell (e.g. haemoglobin formation for erythrocyte production or cytochrome production in proliferating cells). The number of transferrin receptors in the plasma membrane increases in proliferating cells and the number in the liver is increased by cytokines during infection. This results in a lower concentration of iron in the blood which decreases the proliferation of invading pathogens (Chapters 15 and 18). 

Some proteins are imported into cells from the surrounding medium examples in eukaryotes include low-density lipoprotein (LDL), the iron-carrying protein transferrin, peptide hormones, and circulating proteins destined for degradation. The proteins bind to receptors in invaginations of the membrane called coated pits, which concentrate endocytic receptors in preference to other cell-surface proteins. The pits are coated on their cytosolic side with a lattice of the protein clathrin, which forms closed polyhedral structures (Fig. 27-40). The clathrin lattice grows as more recep-... 

A solution of the iron-transport protein, transferrin (Figure 7-4), can be titrated with iron to measure the transferrin content. Transferrin without iron, called apotransferrin, is colorless. Each molecule, with a molecular mass of 81 000, binds two Fe3+ ions. When iron binds to the protein, a red color with an absorbance maximum at a wavelength of 465 nm develops The absorbance is proportional to the concentration of iron bound to the protein. Therefore, the absorbance may be used to follow the course of a titration of an unknown amount of apotransferrin with a standard solution of Fe3+. 

Microequilibrium constants for binding of metal to a protein. The iron-transport protein, transferrin, has two distinguishable metal-binding sites, designated a and b. The microequilibrium formation constants for each site are defined as follows ... 

Transferrin of blood plasma is encoded by a separate gene but has a similar structure. Transferrin of chickens appears to be identical to conalbumin of egg whites. The iron-binding proteins of body fluids are sometimes given the group name siderophilins. Transferrins may function not only in transport of iron throughout the body but also as iron buffers that provide a relatively constant iron concentration within tissues. 

Apoferritin is synthesized in response to several factors, including the presence of iron. Added iron is taken up by the iron transport protein transferrin, which then binds to receptor sites on several types of cells which store iron.1114,1115... 

The transferrins are proteins that bind and transport iron as peIII 16-U.8 They indude lactoferrin from milk, ovotransferrin from egg white, and serum transferrin from a range of organisms. Uteroferrin, considered in Section 62.1.5.5.2 on the purple acid phosphatases, is an iron-binding protein with phosphatase activity, that has been proposed to transport iron from maternal to foetal circulation.824 826 There are distinct differences between the iron-binding sites in uteroferrin and transferrin, and so uteroferrin will not be discussed in this section. 

Lactofenin, transferrin Iron-binding proteins with effects apparently similar to ETDA... 

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