Serum Albumin: A Multifaced Enzyme

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.

Keywords: aldolase activity; anti-oxidant activity; enolase activity; enzymatic properties; esterase activity; glucuronidase activity; human serum albumin; human serum heme-albumin; peroxidase activity.

Figure 1

Three-dimensional structure of HSA (PDB ID: 1AO6) [40]. Fatty acids (FA) bound to specific sites are rendered as space-fill (gray). The heme is rendered as sticks (red). The picture has been drawn with UCSF-Chimera package [45].

Figure 2

Structural environment of the HSA:aspirin complex (PDB ID: 2I2Z) [97] and of the HSA:salicylic acid adduct (PDB ID: 2I30) [97]. Acetyl-Lys199 and Lys199 residues are showed in green. Hydrogen bonds are shown in blue dash lines. Salicylic acid is rendered in sticks (black). Pictures have been drawn with UCSF-Chimera package [45].

Figure 3

Met and Cys residues involved in HSA redox reactions. Met residues are shown as orange spheres, whereas Cys residues are depicted as yellow spheres. The picture has been drawn with UCSF-Chimera package [45].

Figure 4

Scheme of the (pseudo-)enzymatic properties of HSA-heme-Fe. Exa-coordinated HSA-Tyr161-heme-Fe(III)-His146 indicates the inactive heme-protein whereas pentacoordinated HSA-Tyr161-heme-Fe(III) indicates the active form. HSA-Tyr-161-heme-Fe(III)* is the active HSA-Tyr-161-heme-Fe(III); S is the substrate; HSA-Tyr-161-heme-Fe(III)-S is the HSA-Tyr-161-heme-Fe(III) substrate adduct, HSA-Tyr161--heme-Fe(III)*-S is the active HSA-Tyr161-heme-Fe(III) substrate adduct.