Abstract
Human serum albumin (HSA) is the most abundant protein in plasma, contributing actively to oncotic pressure maintenance and fluid distribution between body compartments. HSA acts as the main carrier of fatty acids, recognizes metal ions, affects pharmacokinetics of many drugs, provides the metabolic modification of some ligands, renders potential toxins harmless, accounts for most of the anti-oxidant capacity of human plasma, and displays esterase, enolase, glucuronidase, and peroxidase (pseudo)-enzymatic activities. HSA-based catalysis is physiologically relevant, affecting the metabolism of endogenous and exogenous compounds including proteins, lipids, cholesterol, reactive oxygen species (ROS), and drugs. Catalytic properties of HSA are modulated by allosteric effectors, competitive inhibitors, chemical modifications, pathological conditions, and aging. HSA displays anti-oxidant properties and is critical for plasma detoxification from toxic agents and for pro-drugs activation. The enzymatic properties of HSA can be also exploited by chemical industries as a scaffold to produce libraries of catalysts with improved proficiency and stereoselectivity for water decontamination from poisonous agents and environmental contaminants, in the so called “green chemistry” field. Here, an overview of the intrinsic and metal dependent (pseudo-)enzymatic properties of HSA is reported to highlight the roles played by this multifaced protein.
Highlights
Accepted: 15 September 2021Human serum albumin (HSA) is the most abundant protein in plasma, representing the main determinant of the oncotic pressure and of fluid distribution between body compartments [1,2,3,4,5,6]
HSA plays a pivotal role in heme scavenging acting as a depot and a carrier of the macrocycle; HSA transfers the macrocycle from high- and low- density lipoproteins (i.e., HDL and LDL, respectively) to hemopexin
In the presence of myristate, several drugs co-bind to the FA7 site. This suggests that myristate causes a conformational change(s) of the binding site resulting in the formation of three non-overlapping secondary sites able to recognize anesthetics, anticoagulants, antineoplastics, antiretrovirals, and non-steroidal anti-inflammatory drugs (NSAIDs) [13,41,73] (Table S1)
Summary
Human serum albumin (HSA) is the most abundant protein in plasma, representing the main determinant of the oncotic pressure and of fluid distribution between body compartments [1,2,3,4,5,6]. HSA is the main carrier of endogenous and exogenous ligands, including fatty acids (FAs), nucleic acids, hormones, metals, toxins, and drugs, accounts for most of the pro- and anti-oxidant capacity of plasma, and displays (pseudo)enzymatic properties [4,7,8,9,10,11,12,13]. The HSA-heme-Fe complex displays globin-like catalytic properties including peroxynitrite scavenging and catalase and peroxidase activities [4,14,15,16,17,18]. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. An overview of the intrinsic and metal dependent (pseudo-)enz properties of HSA is reported to highlight the multiple roles played by this mul protein
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