The physicochemical and biological properties of alpha-fetoprotein depend of its ligand environment

Abstract

The majority of studies have concentrated on the endocrine and immunological roles of alpha-fetoprotein (AFP). These studies have been strongly orientated and sustained by research showing that rat and mouse AFPs competitively bind estrogen and non-esterified fatty acids. AFPs of other species, such as humans, are not estrogenophilic but all those studied to date bind NEFAs tightly. Endogenous ligands can greatly influence the conformation of the protein and consequently its biological activity. AFP may have three possible mechanisms of action: a) Murine AFP may be a modulatory element of estrogen expression which determines, under the control of NEFAs the concentration of the active free steroid. b) The protein could be transformed by bound ligands, so enhancing or inhibiting its binding to a target cell receptor, and consequently modifying its biological activity. AFP per se, can be the regulatory element. c) AFPs of all species can work as fatty acid binding proteins and modulate the availability of free NEFAs (not bound to protein). These free NEFAs can, in turn, act positively or negatively on various proteins involved in the pathways of the transfer of the steroid and peptide informations leading to cell multiplication or differentiation.