The liver synthesizes approximately 12 g of albumin per day, representing about 25% of total hepatic protein synthesis and half its secreted protein. About 40% of the body’s albumin circulates in the plasma, where it accounts for roughly three-fifths of total plasma protein by weight (3.4-4.7 g/dL). The remainder resides in the extracellular space. Because of its relatively high concentration, albumin is thought to contribute 75 to 80% of the osmotic pressure of human plasma. Like most other secreted proteins, albumin is initially synthesized as a preproprotein. Its signal peptide is removed as it passes into the cisternae of the rough endo plasmic reticulum. Subsequently, a second hexapeptide is cleaved from the new N-terminus as it moves along the secretory pathway.
Mature human albumin consists of a single polypeptide chain, 585 amino acids in length, that is organized into three functional domains. Its ellipsoidal conformation is stabilized by a total of 17 intrachain disulfide bonds. A major role of albumin is to bind to and transport numerous ligands. These include free fatty acids (FFA), calcium, certain steroid hormones, bilirubin, copper, and tryptophan. A variety of drugs, including sulfonamides, penicillin G, dicumarol, and aspirin, also bind to albumin; a finding with important pharmacologic implications. Preparations of human albumin have been widely used in the treatment of burns and of hemorrhagic shock.
Some humans suffer from genetic mutations that impair their ability to synthesize albumin. Individuals whose plasma is completely devoid of albumin are said to exhibit analbuminemia. Surprisingly, persons suffering from analbuminemia display only moderate edema. Depressed synthesis of albumin also occurs in a variety of diseases, particularly those of the liver, which manifests as a decrease in the ratio of albumin to globulins (decreased albumin-globulin ratio). The synthesis of albumin decreases relatively early in conditions of protein malnutrition, such as kwashiorkor.
