Serum Albumin Binding and Esterase Activity: Mechanistic Interactions with Organophosphates

Abstract

The albumin molecule, in contrast to many other plasma proteins, is not covered with a carbohydrate moiety and can bind and transport various molecules of endogenous and exogenous origin. The enzymatic activity of albumin, the existence of which many scientists perceive skeptically, is much less studied. In toxicology, understanding the mechanistic interactions of organophosphates with albumin is a special problem, and its solution could help in the development of new types of antidotes. In the present work, the history of the issue is briefly examined, then our in silico data on the interaction of human serum albumin with soman, as well as comparative in silico data of human and bovine serum albumin activities in relation to paraoxon, are presented. Information is given on the substrate specificity of albumin and we consider the possibility of its affiliation to certain classes in the nomenclature of enzymes.

Beyond esterase‐like activity of serum albumin. Histidine‐(nitro)phenol radical formation in conversion cascade of p‐nitrophenyl acetate and the role of infrared light

“…Augmented cooperativeness of H‐bonds should effectively aid the proton transfer mechanism. Directed proton transfer was recognized to be essential for esterase‐like activity of BSA as well as for induction of phenoxyl radical . Furthermore, the cooperativeness means more polarized bonds and water dipoles resulting in higher nucleophilic potential of the latter, and the nucleophilic attack of water is involved in both the deacetylation of BSA on hydrolysis of p ‐NPA as well as in the removal of nitro group from p ‐NP .…”

“…Serum albumin, the most abundant protein in blood plasma, unlike many other plasma proteins in not covered by carbohydrate moiety and therefore, serves as a transporter for variety of endogenous and exogenous compounds. 1,2 It is a carrier for metal ions, fatty acids, or nitric oxide among others. It also to a large extent defines fate of many drugs or toxic substances by transporting them to the place of their action or biotransformation.…”

“…In any case, it has been recognized that tyrosine (first of all Tyr411 but also Tyr150) is the primary residue responsible for catalytic activity of serum albumin toward esters. 2 Deprotonation of the catalytic tyrosine is prerequisite for effective hydrolysis. In fact, among serum albumins from different species, those having the lowest ionization constant for tyrosine (in particular human serum albumin followed by BSA) are the most effective in the hydrolysis of p-nitrophenyl esters.…”

A possible link between polyunsaturated fatty acids and uremic toxins from the gut microbiota in hemodialysis patients: A hypothesis

“…HSA is the most abundant plasma protein in the bloodstream and is recognized as the main means of transport for endogenous and exogenous compounds, including fatty acids, bilirubin, hormones, metabolites, amino acids, minerals such as Zn and Cu and drugs . Sudlow et al proposed that HSA has two specific drug binding sites, site I and site II, which are assigned to subdomains IIA and IIIA, respectively .…”

“…11,12 HSA is the most abundant plasma protein in the bloodstream and is recognized as the main means of transport for endogenous and exogenous compounds, including fatty acids, bilirubin, hormones, metabolites, amino acids, minerals such as Zn and Cu and drugs. 13 Sudlow et al proposed that HSA has two specific drug binding sites, site I and site II, which are assigned to subdomains IIA and IIIA, respectively . 14,15 Most of the circulating uremic toxins are found to interact with both binding sites Sudlow I and II, which are located in the subdomains IIA and IIIA, via electrostatic and/or van der Waals forces (binding affinity).…”