RELEASE OF RETINOL AND DENATURATION OF ITS PLASMA CARRIER, RETINOL-BINDING PROTEIN

Background: Retinol is tightly packed inside the structure of its plas ma carrier (retinol-binding protein, REP). it was found that retinol r elease from REP to aqueous solutions is facilitated by either Very low pH or very high temperatures (i.e. by non-physiological conditions th at cause protein denaturation). it was also found that alcohols induce protein conformational transitions to denatured states. On this basis , it may be suggested that retinol release in vivo is facilitated by t he partial unfolding of the carrier resulting from the concerted actio n of the moderate local decrease of pH and the moderate local decrease of dielectric constant in proximity to the target membranes. Results: In vitro, at 37 degrees C, retinol is removed from its plasma carrier by the concerted action of the moderately low pH and the moderately l ow dielectric constant of solutions containing a low ionic strength bu ffer and methanol in variable proportions. Release of retinol is accom panied by a conformational transition of REP from the native to the mo lten-globule state. Conclusions: The physiological function of REP - t argeted delivery of retinol is mimicked in vitro by the facilitated re lease of retinol (associated with a partial unfolding of the protein c arrier) in solutions exhibiting pH and dielectric constant values that are within the range of Values expected in the in vivo microenvironme nt.