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Novel Insights into the Pleiotrophic Effects of Human Serum Albumin in Health and Disease.


Biochim Biophys Acta. 2013 Apr 17;


Authors: Ha CE, Bhagavan NV


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. SCOPE OF REVIEW: This review discusses the pleiotropic biochemical effects and their relevance to physiologic functions of albumin. MAJOR 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 and, 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, 3) The formation of modified albumin during myocardial ischemia, its diagnostic significance, and HSA's role in cardiovascular disease. GENERAL SIGNIFICANCE: 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.

PMID: 23602811 [PubMed - as supplied by publisher]