Uptake and Metabolism of Retinol (vitamin A) in the Isolated Perfused Rat Liver.

The isolated perfused liver was employed to study various aspects of retin01-C~~ metabolism. The rate of uptake of retinol, retinal, retinoic acid, and retinol acetate was rapid (first-order rate constant, k = 0.12-0.16 min-') during the first 3-10 min of perfusion, and then decreased quickly. After 1 hr of perfusion, 5040% of perfusate retinal-Cl4, 2530% of retinol-c", and 20% of retinol-C14 acetate were found in the liver as retinol-C14 ester, and about 10% of the original perfusate radioactivity appeared in the bile as a group of watersoluble metabolites. The amount of retinol ester formed in the liver during 1 hr was linearly dependent on the concentration of retinol in the perfusate over the range of 3 to 1000 pgg/100 ml. Serum, bile salt, or prior injections of India ink had no apparent effect on the formation and storage of retinol ester during perfusion. Only the water-soluble metabolites, but not retinol and its associated derivatives, were released into the perfusate and bile. After 1 hr of perfusion, about 20% of the retinoic acid-C14 was found in the liver as free retinoic acid, and 5% was present in a nonionic fraction.