Transferrin
Siderophores

DEFINITION

Serum Transferrin is a beta-globulin that transports iron in the plasma. It is a glycoprotein that binds iron very tightly but reversibly. When not bound to iron, it is known as apotransferrin. Although iron bound to transferrin is less than 0.1% (4 mg) of the total body iron, it is the most important iron pool, with the highest rate of turnover (25 mg/24 h). This turnover accounts for most of the daily internal iron exchange between body tissues.

Database	Link
Wikigenes	URL
GeneCards	URL
iHOP	URL
OMIM	URL
Entrez Gene	URL

CHEMICAL STRUCTURE AND IMAGES

When relevant for the function

• Primary structure

Transferrin has a molecular weight of around 80 kiloDaltons and contains 2 specific high-affinity Fe(III) binding sites. The affinity of transferrin for Fe(III) is extremely high (1023 M-1 at pH 7.4) but decreases progressively with decreasing pH below neutrality.

• Secondary structure
• Tertiary structure
• Quaternary structure

Transferrin is a glycoprotein Define better ???

Protein Aminoacids Percentage
The Protein Aminoacids Percentage gives useful information on the local environment and the metabolic status of the cell (starvation, lack of essential AA, hypoxia)

SYNTHESIS AND TURNOVER

Albumin and transferrin synthesis during development in the rat 1974

Intracellular Aspects of Transferrin Synthesis and Secretion in the Rat 1971

Albumin and transferrin synthesis are increased in H4 cells by serum from analbuminemic or nephrotic rats 1994

Stimulatory effect of 1,25-dihydroxyvitamin D3 on transferrin synthesis in primary cultures of adult rat hepatocytes. 1990

mRNA synthesis
protein synthesis
post-translational modifications
degradation

CELLULAR FUNCTIONS

Cellular localization,

• Transferrin is a serum protein, synthesized mainly in the liver: but other sources such as the brain also produce this molecule .

Biological function

• The main role of transferrin is to deliver iron from absorption centres in the duodenum and red blood cell macrophages to all tissues. Predominantly, transferrin plays a key role where erythropoiesis and active cell division occur.

• Transferrin Iron affinity is modulated by bicarbonate

• Role of Bicarbonate
  • Iron, infection, and the role of bicarbonate
  • Deferoxamine Reduces Early Metabolic Failure Associated With Severe Cerebral Ischemic Acidosis in Dogs 1995
  • Rationalization of the strength of metal binding to human serum transferrin 1996
  • Dealing with iron: Common structural principles in proteins that transport iron and heme 2003
  • The formation of Fe3+-transferrin-CO3 via the binding and oxidation of Fe2+ 1981
  • Transferrin. Interactions of lactoferrin with hydrogen carbonate 1997

elevated lactic acid but not carbonic acid leads to proton-induced dissociation of carbonate bonds in the transferrin-iron complex

Transferrin carries also Mn++

REGULATION

DIAGNOSTIC USE

High serum transferrin levels are found in patient with iron deficiency
Low levels are found in those with iron overload, hepatopathy and malnutrition.

Serum transferrin concentration = 1,6-3,6 g/l
Transferrin half-life = 8-10 days
Transferrin saturation = 20-45 %

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Transferrin metabolism in alcoholic liver disease. 1985

Transferrin Iron saturation is reduced in pregnancy

Normal pregnancy is characterized by a state of decreased insulin sensitivity, as well as accelerated lipolysis and ketogenesis. The concentration of serum ketones has been estimated to be two to four times greater than in the nonpregnant state.1, 5 In addition, pregnant women have a respiratory alkalosis, lowering the serum bicarbonate concentration, thus reducing the capacity to buffer hydrogen ions.
Normoglycemic diabetic ketoacidosis in pregnancy 2008

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Iron transferrin regulates hepcidin synthesis in primary hepatocyte culture through hemojuvelin and BMP2/4 2007

Repression of {alpha}-Fetoprotein Gene Expression under Hypoxic Conditions in Human Hepatoma Cells 2002

Melanoferrin

Site

Transferrin receptor mediated Iron uptake

Figure 3. Cellular uptake of iron through the Tf system via receptor-mediated endocytosis.

Transferrin: structure, function and potential therapeutic actions.

Transferrin/transferrin receptor-mediated drug delivery.

The transferrin receptor part II: targeted delivery of therapeutic agents into cancer cells.

Transferrin and transferrin receptors

Transferrin

Bella Tesina 2008

Graphs show intracellular pH as determined by 31P magnetic resonance spectroscopy and estimated intracellular bicarbonate levels during ischemia and reperfusion (mean values±SEM). Zero time indicates the start of reperfusion. Time scale is compressed after 60 minutes to emphasize early transients. Groups are saline vehicle, n=8; free deferoxamine (DFO), n=8; hydroxyethyl starch vehicle (HES), n=6; and hydroxyethyl starch–conjugated deferoxamine (HES-DFO), n=5. *P<.05 from respective vehicle group.