title: Novel insights into the pleiotropic effects of human serum albumin in health and disease.
abstract: BACKGROUND
  Human serum albumin is the principal protein in human serum. It participates in regulation of plasma oncotic pressure and transports endogenous and exogenous ligands such as thyroxine, free fatty acids, bilirubin, and various drugs. Therefore, studying its ligand binding mechanism is important in understanding many functions of the protein.
  
  
  METHODS
  This review discusses the pleiotropic biochemical effects and their relevance to physiologic functions of albumin.
  
  
  CONCLUSIONS
  Although HSA is traditionally recognized for its ligand transport and oncotic effects in human circulation, our studies have revealed its participation in several other important physiological functions. In some instances, it may function as a catalyst. Pleiotropic properties of HSA have been exploited by development of recombinant HSA and its mutants, and the use of these recombinant proteins in studies with various biochemical and biophysical techniques. These studies allowed us to obtain new insights on the diverse roles of HSA in human physiology. The following aspects of HSA were discussed in this review: 1) HSA and its mutants' role in thyroxine transport, 2) structural details of the ligand binding functions of HSA to ligands such as warfarin, digoxin, halothane anesthetics, nitric oxide, bilirubin, free fatty acids, etc, and 3) the formation of modified albumin during myocardial ischemia, its diagnostic significance, and HSA's role in cardiovascular disease.
  
  
  CONCLUSIONS
  The appreciation and understanding of structural details and new physiological roles has provided a renewed interest in HSA research. Specific structural information gained on various mechanisms of HSA-ligand interaction can be used to develop a model to better understand protein-drug interactions, aid in the development of new drugs with improved pharmacokinetic effects, and ultimately be used to improve the quality of healthcare. This article is part of a Special Issue entitled Serum Albumin.
authors.affiliation: Department of Native Hawaiian Health, University of Hawaii, Honolulu 96813, USA. Electronic address: chungeun@hawaii.edu.
authors.forename: Chung-Eun
authors.initials: CE
authors.lastname: Ha
authors.forename: Nadhipuram V
authors.initials: NV
authors.lastname: Bhagavan
mesh_terms: D001692:Biological Transport; D003324:Coronary Artery Disease / Q000378:metabolism; D018360:Crystallography, X-Ray; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology; D008024:Ligands; D008958:Models, Molecular; D009203:Myocardial Infarction / Q000503:physiopathology; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D013974:Thyroxine / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D008024:Ligands; D012709:Serum Albumin; D013974:Thyroxine
keywords: Familial dysalbuminemic hyperthyroxinemia; Fatty acid; Human serum albumin; Protein–ligand interaction; Thyroxine; Warfarin