What is transferrin and how does it work?
Your liver makes transferrin. When your body's stores of iron run low, your liver produces more transferrin in order to get more iron into your blood. Iron plays many important roles in your body, including helping your red blood cells carry oxygen to the cells in your body. Nearly all the iron in your body is normally attached to transferrin.
How is iron delivered to cells by transferrin?
The delivery of iron to cells by transferrins is a receptor-mediated and controlled process. Cells regulate the amount of iron they receive from the extracellular environment by varying transferrin receptor expression.
How are transferrins transported in the blood?
Transferrins are glycoproteins that are often found in biological fluids of vertebrates. When a transferrin protein loaded with iron encounters a transferrin receptor on the surface of a cell, e.g., erythroid precursors in the bone marrow, it binds to it and is transported into the cell in a vesicle by receptor-mediated endocytosis.
How is transferrin transported in the endocytic cycle?
Transport mechanism. The receptor with its ligand bound transferrin is then transported through the endocytic cycle back to the cell surface, ready for another round of iron uptake. Each transferrin molecule has the ability to carry two iron ions in the ferric form ( Fe3+ ).
How does iron bound transferrin enter the cell?
Cellular uptake of Tf-bound iron. Transferrin (Tf) is bound by two atoms of Fe3+ and circulates in plasma until reaching a target cell. It binds the transferrin receptor (TfR) on the plasma membrane of the cell, and then the Fe-Tf and TfR complex is endocytosed by the cell.
Where is transferrin found in the cell?
Transferrin is a protein synthesized almost exclusively in the liver and is secreted into the blood. It is the principal transport protein for iron throughout the body and delivers approximately 70% to the bone marrow for incorporation into hemoglobin within RBCs.
What does transferrin transport in plasma?
Transferrin is a blood-plasma glycoprotein, which plays a central role in iron metabolism and is responsible for ferric-ion delivery. Transferrin functions as the most critical ferric pool in the body. It transports iron through the blood to various tissues such as the liver, spleen, and bone marrow.
What does transferrin transport around the body?
Transferrin is the major iron transport protein (transports iron through blood). Fe3+ is the form of iron that binds to transferrin, so the Fe2+ transported through ferroportin must be oxidized to Fe3+.
Why is transferrin used in cell culture?
Transferrin is an essential ingredient used in cell culture media due to its crucial role in regulating cellular iron uptake, transport, and utilization. It is also a promising drug carrier used to increase a drug's therapeutic index via the unique transferrin receptor-mediated endocytosis pathway.
Can transferrin cross blood brain barrier?
Transferrin and its receptors play an important role during the uptake and transcytosis of iron through blood-brain barrier (BBB) endothelial cells (ECs) to maintain iron homeostasis in BBB endothelium and brain.
How is iron transported across the plasma membrane?
Iron is initially solubilized by reduction and Fe(2+) is transported across the cell membrane by a carrier-mediated transport process. This is followed by intracellular transfer of iron to the basolateral enterocyte membrane with subsequent transfer and release of iron to transferrin in the portal blood.
What is transferrin quizlet?
Transferrin is a binding protein that binds to free Iron and transports it in the blood to other cells.
Where is the transferrin receptor located?
Transferrin receptors are expressed on the surfaces of all cells in concert with their need for iron. A truncated form of the extracellular domain of the receptor is produced by proteolytic cleavage and is present in the plasma in direct proportion to the total number of receptors expressed in all body tissues.
How is iron transported after absorption?
Once in the absorptive cells, the iron may follow one of several possible pathways. The absorbed iron can be transferred across the cell to blood, it can be stored in ferritin, or it can enter the mitochondria. In iron-deficient animals, most of the iron is transported across the cell and into the blood (Figure 3-4b).
How is transferrin produced?
The liver synthesizes transferrin and secretes it into the plasma. Transferrins are produced locally in the testes and CNS. These two sites are relatively inaccessible to proteins in the general circulation (blood:testis barrier, blood:brain barrier).
How is transferrin regulated?
Transferrin expression is regulated by the iron state of the cell and by certain hormones. The liver is the primary site where transferrin is synthesized and secreted into serum. Iron can regulate transferrin synthesis but relatively little is known of the mechanism of iron action.
In which zone of the protein spectrum is transferrin located?
The gene coding for transferrin in humans is located in chromosome band 3q21.
What is transferrin quizlet?
Transferrin is a binding protein that binds to free Iron and transports it in the blood to other cells.
Is transferrin produced in the liver?
Transferrin (Trf), a serum-abundant metal-binding protein, is primarily synthesized in the liver.
What is transferrin in biology?
Transferrin is an abundant serum metal-binding protein best known for its role in iron delivery. The human disease congenital atransferrinemia and animal models of this disease highlight the essential role of transferrin in erythropoiesis and iron metabolism.
What is the absence of transferrin?
An absence of transferrin results from a rare genetic disorder known as atransferrinemia, a condition characterized by anemia and hemosiderosis in the heart and liver that leads to heart failure and many other complications.
What happens when plasma transferrin levels rise?
When plasma transferrin levels rise, there is a reciprocal decrease in percent transferrin iron saturation, and a corresponding increase in total iron binding capacity in iron deficient states A decreased plasma transferrin can occur in iron overload diseases and protein malnutrition.
What is the immune system associated with transferrin?
Immune system. Transferrin is also associated with the innate immune system. It is found in the mucosa and binds iron, thus creating an environment low in free iron that impedes bacterial survival in a process called iron withholding. The level of transferrin decreases in inflammation.
What is the shape of a transferrin receptor?
The shape of a transferrin receptor resembles a butterfly based on the intersection of three clearly shaped domains. Two main transferrin receptors found in humans denoted as transferrin receptor 1 (TfR1) and transferrin receptor 2 (TfR2).
How do transferrin glycoproteins work?
Transferrin glycoproteins are able to bypass the blood-brain barrier via receptor-mediated transport for specific transferrin receptors found in the brain capillary endothelial cells. Due to this functionality, it is theorized that nanoparticles acting as drug car riers bound to transferrin glycoproteins can penetrate the blood-brain barrier allowing these substances to reach the diseased cells in the brain. Advances with transferrin conjugated nanoparticles can lead to non-invasive drug distribution in the brain with potential therapeutic consequences of central nervous system (CNS) targeted diseases (e.g. Alzheimer's or Parkinson's disease).
What factors affect iron release rate?
Iron release rate is dependent on several factors including pH levels, interactions between lobes, temperature, salt, and chelator. The receptor with its ligand bound transferrin is then transported through the endocytic cycle back to the cell surface, ready for another round of iron uptake.
How many amino acids are in transferrin?
In humans, transferrin consists of a polypeptide chain containing 679 amino acids and two carbohydrate chains. The protein is composed of alpha helices and beta sheets that form two domains. The N- and C- terminal sequences are represented by globular lobes and between the two lobes is an iron-binding site.
What are the four coordination sites in the transferrin molecule?
The remaining four coordination sites are those from the transferrin molecule including an aspartic carboxylate oxygen, two tyrosine phenolate oxygens, and a histidine nitrogen. At any given time, about one third of the transferrin’s binding sites are filled.
Why is transferrin important?
Transferrin has become an important biomarker for good health in the clinical setting, as it can reveal if a patient has functional iron depletion. This bio-marker, of course, will give a physician insight into a patient’s pathology, as well as which treatment plan will be most suitable moving forward.
What are the symptoms of transferrin saturation?
Symptoms may include pale coloration, fatigue, irritability, and shortness of breath. Anemia is defined as having low numbers of red blood cells, however one type is categorized by iron-deficiency.
What is anemia in the body?
Anemia is defined as having low numbers of red blood cells, however one type is categorized by iron-deficiency. When iron levels run low in our bodies’ stores, our livers will upregulate transferrin synthesis in the healthy individual.
How many amino acids are in transferrin?
Structurally speaking, Transferrin is a polypeptide chain consisting of two carbohydrate chains and almost seven hundred amino acids. Transferrin has two homologous globular lobes, the N- and C- terminals comprised of alpha helices and beta sheets, with an iron binding site in between. The site itself is a six iron coordinate site occupied by ...
How much iron is in the circulatory system?
Safe shuttling through our circulatory system is the answer. While humans contain about 3.7 grams of iron in our bodies, much of which comes from our diets, 2.5 grams will be “locked” inside hemoglobin with iron. Hemoglobin can then assume its role in transporting oxygen through the blood.
Why is iron important to life?
Humans use iron for many cellular processes but perhaps the most important is iron’s ability to bind oxygen.
What is the purpose of transferrin?
Transferrin is the physiologically appropriate method for providing iron to cells in culture. The delivery of iron using transferrin has historically been part of an iron management program in biomanufacturing systems for production of therapeutic proteins, such as monoclonal antibodies. Efforts to move to animal protein-free and protein-free cell culture systems have motivated developers to seek small molecule alternatives to transferrin. These are generally iron chelators. Iron chelators should be used with great caution because many chelators do not control the redox cycling of iron that contributes to oxidative stress.
What are the functions of transferrins in cell culture?
Primary Functions of Transferrin in Cell Culture Systems: Transferrins facilitate extracellular iron storage, and transport. Transferrins are important extracellular antioxidants. They bind iron so tightly under physiological conditions that virtually no free iron exists to catalyze the production of free radicals.
How many atoms of ferric iron bind transferrin?
Two atoms of ferric iron bind transferrin with distinctly different affinities. The first and second iron atom stability constant are approximately 10 30 and 10 27, respectively. Virtually no iron is free to participate in free radical chemistry when transferrin is present in cell culture medium with molar ratios of transferrin to iron greater ...
How does iron transferrin work?
Two iron-loaded transferrin molecules bind to one transferrin receptor. Once bound, they are transferred into acidic endosomes within the cell’s interior. At reduced pH, the iron is released and incorporated into intracellular proteins and the storage molecule ferritin. The apo-transferrin (iron free) is recycled back to the exterior of the cell and released. Each transferrin receptor cycle can deliver up to four atoms of iron.
Is iron free to participate in free radical chemistry?
Virtually no iron is free to participate in free radical chemistry when transferrin is present in cell culture medium with molar ratios of transferrin to iron greater than one. When the iron concentration in media exceeds the tranferrin’s total iron binding capacity (TIBC), free iron can exist in the medium. Unbound iron can participate in free ...
Does iron binding increase transferrin?
The stability of transferrin is increased by conformational changes induced by iron binding. Iron binding increases the affinity of transferrin for cell transferrin receptors. The glycosylation pattern on transferrin does not appear to have a significant effect on its binding to the transferrin receptor. However, it may affect transferrin binding ...
What is this test?
This test measures the amount of the protein transferrin in your blood.
What do my test results mean?
Test results may vary depending on your age, gender, health history, the method used for the test, and other things. Your test results may not mean you have a problem. Ask your healthcare provider what your test results mean for you.
How is this test done?
The test is done with a blood sample. A needle is used to draw blood from a vein in your arm or hand.
What might affect my test results?
Aspirin, antibiotics, and birth control pills can affect your results.
How to check iron levels?
Your healthcare provider may also order other tests, including: 1 Complete blood count, or CBC 2 Tests to measure how much iron is in your blood 3 Measurement of ferritin, a protein that holds most of your body's iron reserves 4 Stool tests
What is transferrin measured in?
Transferrin may also be measured using a value called total iron-binding capacity (TIBC). Results are given in micrograms per deciliter (mcg/dL). Normal values are 250 to 450 mcg/dL. A higher level means that you may have iron-deficiency anemia.
What does it mean when you have anemia?
In general, anemia means you have a low number of red blood cells. One type of anemia is iron-deficiency anemia. If you have this type, you don't have enough iron to properly make hemoglobin.
What causes transferrin to decrease?
2) Inflammation. As mentioned above, transferrin is a negative acute phase protein. When the liver increases the production of inflammation-associated proteins (e.g. CRP, ferritin) it decreases the production of transferrin. A number of conditions such as infection and cancer can decrease transferrin levels [ 6, 7, 28 ].
How to reduce transferrin?
If your transferrin is low due to iron overload: 1 Avoid foods that are high in iron, such as red meat, fish, and poultry [ 43 ]. 2 Eat more foods that reduce iron absorption such as fiber and phytic acid (from whole grains) and chili [ 44, 45, 46 ]. 3 Drink more coffee, cocoa, green tea and herbal teas, such as chamomile, lime flower, pennyflower, mint, and vervain with meals – all of these decrease iron absorption [ 15, 47, 14, 16, 48, 17 ]. 4 Avoid using cast iron utensils. They increase the amount of iron in meals [ 12 ]. 5 Get more exercise. Regularly exercising will help prevent your iron levels from becoming too high [ 49, 50 ].
Why is transferrin high?
The most common cause of high transferrin levels is iron deficiency [ 8, 9, 10 ].
How to measure transferrin levels?
Transferrin levels can be measured directly with a blood test. Alternatively, they can also be measured indirectly using total iron binding capacity ( TIBC ).
What foods should I avoid if my transferrin is low?
If your transferrin is low due to iron overload: Avoid foods that are high in iron, such as red meat, fish, and poultry [ 43 ]. Eat more foods that reduce iron absorption such as fiber and phytic acid (from whole grains) and chili [ 44, 45, 46 ].
What influences transferrin levels?
Iron availability dictates transferrin production, but transferrin levels are also influenced by inflammation, liver, and kidney disease. Keep reading to learn more about high and low transferrin levels and ways to improve them.
What causes high blood pressure during pregnancy?
Preeclampsia, a condition that causes high blood pressure during pregnancy, is associated with inflammation. Women with preeclampsia can have decreased transferrin levels [ 31, 32 ].
Overview
Occurrence and function
Transferrins are glycoproteins that are often found in biological fluids of vertebrates. When a transferrin protein loaded with iron encounters a transferrin receptor on the surface of a cell, e.g., erythroid precursors in the bone marrow, it binds to it and is transported into the cell in a vesicle by receptor-mediated endocytosis. The pH of the vesicle is reduced by hydrogen ion pumps (H ATPases) to about 5.5, causing transferrin to release its iron ions. Iron release rate is dependen…
Structure
In humans, transferrin consists of a polypeptide chain containing 679 amino acids and two carbohydrate chains. The protein is composed of alpha helices and beta sheets that form two domains. The N- and C- terminal sequences are represented by globular lobes and between the two lobes is an iron-binding site.
The amino acids which bind the iron ion to the transferrin are identical for both lobes; two tyrosines, …
Immune system
Transferrin is also associated with the innate immune system. It is found in the mucosa and binds iron, thus creating an environment low in free iron that impedes bacterial survival in a process called iron withholding. The level of transferrin decreases in inflammation.
Role in disease
An increased plasma transferrin level is often seen in patients with iron deficiency anemia, during pregnancy, and with the use of oral contraceptives, reflecting an increase in transferrin protein expression. When plasma transferrin levels rise, there is a reciprocal decrease in percent transferrin iron saturation, and a corresponding increase in total iron binding capacity in iron deficient states A decreased plasma transferrin can occur in iron overload diseases and protein …
Transferrin and nanomedicine
Many drugs are hindered when providing treatment when crossing the blood-brain barrier yielding poor uptake into areas of the brain. Transferrin glycoproteins are able to bypass the blood-brain barrier via receptor-mediated transport for specific transferrin receptors found in the brain capillary endothelial cells. Due to this functionality, it is theorized that nanoparticles acting as drug carriers bound to transferrin glycoproteins can penetrate the blood-brain barrier allowing these s…
Other effects
Carbohydrate deficient transferrin increases in the blood with heavy ethanol consumption and can be monitored through laboratory testing.
Transferrin is an acute phase protein and is seen to decrease in inflammation, cancers, and certain diseases (in contrast to other acute phase proteins, e.g., C-reactive protein, which increase in case of acute inflammation).
Pathology
Atransferrinemia is associated with a deficiency in transferrin.
In nephrotic syndrome, urinary loss of transferrin, along with other serum proteins such as thyroxine-binding globulin, gammaglobulin, and anti-thrombin III, can manifest as iron-resistant microcytic anemia.