Human Serum Albumin as a ‘Silent Receptor’ for Drugs and Endogenous Substances

Abstract

Most drugs are bound to human serum albumin (HSA) via a few high affinity binding sites and several sites of much lower affinity. There is now increasing evidence that the actual number of high affinity drug-binding sites of HSA is rather small. Thus, each of these binding sites binds several drugs of very different chemical and pharmacological properties with relative high affinity. On the other hand these drug-binding sites can in some cases be very specific and even stereoselective, as demonstrated by the stereospecific binding of drugs to some of these binding sites. The discrepancy between both observations can be explained by the conformational adaptability of the HSA-binding sites.

Uptake of oleate from albumin solutions by rat liver. Failure to detect catalysis of the dissociation of oleate from albumin by an albumin receptor.

“…Thus, the binding affinity of albumin is known to depend on its conformation (30), suggesting that a nonspecific interaction might catalyze dissociation by altering the conformation ofthe albumin molecule. Moreover, albumin is known to bind to many different cell types (8) and some hydrophobic surfaces (31).…”

The role of albumin conformation in the binding of diazepam to human serum albumin

“…It has been established that the binding of the anticoagulant drug warfarin to albumin * is affected by this N-B transition [2]. Miiller and WoUert [8], Fehske et al [9], Brodersen et al [10] and Sudlow et al [11] have demonstrated at least two very specific and selective binding sites to be present on the albumin molecule for a large number of highly bound drugs. These sites are the so-called warfarin and diazepam binding site, also denoted as site I and site II by Sudlow et al [11].…”

Interaction of Bioactive Components Caffeoylquinic Acid Derivatives in Chinese Medicines with Bovine Serum Albumin

“…17) Protein-ligand interactions play important roles in pharmacology and pharmacodynamics. It is widely accepted that the distribution, free concentration, and metabolism of various compounds can be affected as a result of binding to serum albumins in the blood stream.…”