Studies on the transport and cellular distribution of vitamin A in normal and vitamin A-deficient rats with special reference to the vitamin A-binding plasma protein.

The retinol-binding protein (RBP) and thyroxine-binding prealbumin were isolated from rat serum. Under physiological conditions RBP and prealbumin form a protein complex. Rat RBP exhibited characteristics very similar to those previously encountered for the human and monkey counterparts, including the association constant to prealbumin (8 x lo6 M-l). Thyroxine-binding prealbumin in rat is in contrast to its human counterpart the major thyroxine carrying plasma protein. Its molecular weight differs from that of the human protein (51,000 and 62,000, respectively) in spite of its similar binding constant for thyroxine. The role of the vitamin A-transporting protein complex was investigated with respect to the tissue distribution of [3H]vitamin A in normal and vitamin A-deficient rats. It was demonstrated that the hepatocytes which stored virtually all liver vitamin A could rapidly mobilize newly administered vitamin, and the retinol occurred exclusively bound to RBP. The mobilization of liver vitamin A was unaffected by prior actinomycin D treatment of the rats, which suggests that newly synthesized RBP requires retinol for its release from the hepatocytes. An investigation was also undertaken of the role of the kidney as a storage organ for vitamin A. Kinetic m.easurements showed that the kidney received most of its vitamin A from RBP in contrast to the liver which gets its main supply from the chylomicrons. Fractionation of kidney cortex cells on a discontinuous silica gel gradient indicated that most vitamin A resided in tubular cells. The vitamin-containing cell fractions were shown to possess the property to take up RBP in vivo. These results suggest that some vitamin A may reach the kidney by a process of glomerular filtration followed by tubular reabsorption.