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From Proteopedia

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Background

Albumin in general refers to any protein that is water soluble. Albumins are commonly found in blood plasma as a serum transport protein. Other serum transport proteins are: alpha-fetoprotein, vitamin D-binding protein, and afamin.^[1].

Where and how it is synthesized

SA is produced in the liver. Albumin synthesis begins in the nucleus, where genes are transcribed into messenger ribonucleic acid (mRNA). The mRNA is secreted into the cytoplasm, where it is bound to ribosomes, forming polysomes that synthesize preproalbumin. Preproalbumin is an albumin molecule with a 24 amino acid extension at the N terminal peptide. The extension releases the preproalbumin into the rough endoplasmic reticulum. Once inside the endoplasmic reticulum, the leading 18 amino acids of this extension are cleaved, leaving proalbumin (albumin with the remaining extension of 6 amino acids). Proalbumin is the principal intracellular form of albumin. Proalbumin is exported to the Golgi apparatus, where the extension of 6 amino acids is removed before the albumin is secreted by the liver cells. Once synthesized, albumin is secreted immediately; it is not stored in the liver. The serum albmin is distributed to the tissues of the body, a majority of it is distributed in the skin. Albumin is distributed within the vascular compartments of the muscle, skin, liver, gut, and other tissues.^[2].

Function

Serum albumin (SA) is the main protein in blood plasma, it accounts for about 50 percent of the protein in the blood plasma. SA binds to water, cations ( such as Ca2+, Na+, and K+), fatty acids, hormones, bilirubin, and drugs. It transports thyroid hormones, and other hormones that are fat-soluble. It also transports “free” fatty acids to the liver and unconjugated bilirubin. It is also a carrier for two materials necessary for the control of blood clotting: antithrombin, which keeps the clotting enzyme thrombin from working unless it is needed, and heparin cofactor, which is needed for heparin to anticlot. Its main function is to regulate the colloidal osmotic pressure of blood. When plasma proteins, especially albumin, no longer sustain sufficient colloid osmotic pressure to counterbalance hydrostatic pressure, edema develops. Albumin helps in keeping the fluid from the blood from leaking out into the tissues. It serves as a carrier of molecules of low water solubility by isolating their hydrophobic nature in albumins binding sites. ^[3].

Structure

Serum albumin has many high affinity binding sites which are target for many organic and inorganic molecules. It is a globular protein of an ellipsoidal shape and is composed of three structurally similar domains.(I,II, and III) Each of the domains contain two sub domains. (A and B). The domains are stabilized by 17 pairs of disulphide bridges and one free cysteine. Each domain is believed to consist of 6 helices forming a hydrophobic channel with basic and hydrophobic amino acid residues placed at the ends. The domains are not identical. Long-chain fatty acid ions bind with high affinity within the channels. Region 1 of the molecule is specific for binding one or possibly two ions of long chain fatty acids. Region two is less specific and binds: octanoate, tryptophan, chlorazepate, thyroxine, p-iodobenzoate and possibly also chloride. Region 3 binds: bilirubin, Phenol Red, Bromophenol Blue and iopanoate. Region four: strong binding of metal ions such as Cu++ and Ni++. The binding of primary hemin has its own region , 5. ^[4].

Role in Diseases

High levels of albumin, called hyperalbuminemia, is almost always caused by dehydration. Retinol ( vitamin A) deficiency can cause albumin levels to rise because retinol causes the cells to swell with water, this is also the reason too much vitamin A is toxic. Chronic dehydration is treated with zinc and water. Zinc reduces the swelling of the cell caused by increase in take of water. When the body is dehydrated it has high osmolarity, and zinc is discarded, which usually prevents this. Zinc regulates transport of the cellular osmolyte taurine, and albumin is known to increase cellular taurine absorbtion. Low levels of albumin, called hypoalbuminemia, can be caused by liver disease (cirrhosis, and hepatitis), excess excretion in the kidneys (nephritic syndrome), excess loss in bowl (Crohn’s disease) and burns (plasma loss in the skin barrier). ^[5].

Interaction with Drugs

Some drugs that albumin carries are: warfarin, phenobutazone, clofibrate,ibuprofen, and phenytoin. There can be competition between drugs for albumin binding sites, which can cause that particular drug to be free in the plasma and thus increase its potency. Serum albumin levels can affect the half- life of drugs. After absorbtion of the drug into the body, the drug binds to serum proteins, which carry them to their specific areas in the body. ^[6]. The two major binding sites for drugs are sites I and II. Examples of drugs that bind to site I are: warfarin and furosemide. Drugs that bind to site II are: diazepam and diclofenac. ^[7].

References

1. Vincent JL. Relevance of albumin in modern critical care medicine. Best Pract Res Clin Anaesthesiol. Jun 2009;23(2):183-91 2. Rothschild MA, Oratz M, Schreiber SS. Albumin synthesis. 1. N Engl J Med. Apr 6 1972;286(14):748-57. [Medline]. 3. Peralta,Ruben. Hypoalbuminemia.webMD.Apr 15 2010