Human serum albumin: A multifunctional protein

Abstract

Human serum albumin is synthesized in the liver and continuously secreted into the bloodstream. Several receptors are strongly involved in the following distribution and metabolism of the protein. The receptor-albumin interactions can be modified by specific mutations, a finding which could be of pharmaceutical and medical interest. The largest pool of albumin is found in the extravascular spaces although at a lower concentration than in the bloodstream. The higher concentration in the circulation is the main contributor to plasma’s colloid osmotic pressure and to the Gibbs-Donnan effect in the capillaries. Albumin seems to be the quantitatively most important circulating antioxidant, and it has enzymatic properties which are so pronounced that they most probably are of biological importance. The protein’s ability to bind ligands and thereby to serve as an important depot and transport protein for numerous endogenous and exogenous compounds is well studied. Recent work has given much new information about the location and structure of binding sites and about potential ligand interactions. Structural information is also useful when designing new drugs whether the aim is to avoid binding or to make use of the protein’s depot function. Nonbinding therapeutics can get improved stability and benefit from the long biological half-life of albumin by forming complexes with it. The complex formation can take place by enriching the therapeutic with an organic molecule which can bind reversibly or covalently to the protein. If the therapeutic is a polypeptide or protein, fusion proteins can be produced. Albumin also shows promises for targeted drug delivery. This process can be passive and based on the enhanced permeability and retention effect. The effect can be increased by using dimers, polymers, or albumin-based nanoparticles. The targeting process can also be active and based on an interaction between albumin carrying a targeting ligand and cellular receptors.