Effect of vitamin A deficiency on the hydrolysis of retinoyl beta-glucuronide to retinoic acid by rat tissue organelles in vitro.

In keeping with the in vivo observation that the conversion of retinoyl beta-glucuronide (RBG) to retinoic acid (RA) is enhanced in vitamin A-deficient (A-) rats, the relative rates of hydrolysis of RBG to RA by various organelles of liver, kidney and intestine were found to be higher in A- rats than in vitamin A-sufficient (A+) rats (mean ratio 1.28; range 1.05-1.63). The lysosomal fraction of kidney and the microsomal fraction of liver showed the highest ratios for RBG hydrolysis; namely, 1.63 and 1.57, respectively (p < 0.005). The rates of hydrolysis of an ether glucuronide, p-nitrophenyl-beta-D-glucosiduronate (pNPG), were also enhanced in A- rats. The ratios of activities were again highest in kidney lysosomes and in liver microsomes; namely, 1.51 (p < 0.005) and 1.42 (p < 0.05), respectively. The non-ionic detergent, Triton X-100, increased RBG hydrolysis in organelles of A+ (19-27%) more than in those of A- rats (8-14%). The ratios of activities +/- SEM with 0.02% Triton X-100 in organelles of kidney, liver and intestine were 1.25 +/- 0.03, 1.22 +/- 0.03 and 1.24 +/- 0.03 in A+ rats and were 1.11 +/- 0.02, 1.07 +/- 0.02 and 1.13 +/- 0.03, respectively, in A- rats. Thus, Triton X-100 had a significantly greater effect (p < 0.005) on the membranes of A+ rats than on those of A- rats. In conclusion, the increased appearance of RA in the plasma after RBG administration in vivo seems to be caused by enhanced activity of beta-glucuronidases in tissue organelles, augmented in part by better access of the substrate to the membrane-bound enzymes.