Release of retinol and denaturation of its plasma carrier, retinol-binding protein.
BACKGROUND
Retinol is tightly packed inside the structure of its plasma carrier (retinol-binding protein, RBP). It was found that retinol release from RBP to aqueous solutions is facilitated by either very low pH or very high temperatures (i.e. by non-physiological conditions that 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 the partial unfolding of the carrier resulting from the concerted action 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 low dielectric constant of solutions containing a low ionic strength buffer and methanol in variable proportions. Release of retinol is accompanied by a conformational transition of RBP from the native to the molten-globule state.


CONCLUSIONS
The physiological function of RBP-targeted delivery of retinol-is mimicked in vitro by the facilitated release of retinol (associated with a partial unfolding of the protein carrier) in solutions exhibiting pH and dielectric constant values that are within the range of values expected in the in vivo microenvironment.
Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow.
V E
VE
Bychkova
A E
AE
Dujsekina
A
A
Fantuzzi
O B
OB
Ptitsyn
G L
GL
Rossi
D002942:Circular Dichroism; D005453:Fluorescence; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000432:Methanol / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D011487:Protein Conformation / Q000187:drug effects; D011489:Protein Denaturation; D017510:Protein Folding; D012172:Retinaldehyde / Q000378:metabolism*; D012177:Retinol-Binding Proteins / Q000737:chemistry*; D054839:Retinol-Binding Proteins, Plasma; D014364:Tryptophan / Q000737:chemistry
D012177:Retinol-Binding Proteins; D054839:Retinol-Binding Proteins, Plasma; D014364:Tryptophan; D012172:Retinaldehyde; D000432:Methanol