Factors affecting vitamin A transport in animals and man.

The fat-soluble vitamin A has, of necessity, to be transported in the body by carrier proteins since it functions in an aqueous environment. At the same time, control of the distribution of the alcohol form, via specific retinol-binding proteins (RBP), provides additional physiological advantages. The concentration of the amphiphilic molecule is more easily limited in tissue fluids where, if free, it could damage or lyse cell membranes indiscriminately (Dingle & Lucy, 1962) and the presence of a binding site on the carrier protein for specific acceptors in functional cell membranes enables the vitamin to be directed to its targets selectively (Heller, 1975) and in controlled amounts. Bulk transport of the vitamin during its absorption from the intestine to the liver takes place mainly as retinyl esters within the lipid phase of lowdensity lipoproteins (Gangdy, 1960), whereas the physiologically-active retinol circulates attached to a hydrophobic cleft on plasma retinol-binding protein (holoRBP) (21 ooo MW) synthesized and secreted by the liver (Kanai et al. 1968). In plasma, holoRBP forms a I : I complex with thyroxine-binding prealbumin (TBPA) (54 ooo MW); the formation of this larger complex is regarded as important in preventing the rapid loss of the holoRBP by ultrafiltration through the kidney and it also increases the stability of the retinol bound to RBP (Raz et al. 1970). A third binding site on the latter enables it to bind to the membrane acceptors of target cells so that the retinol can be released to cross the membrane and be taken up by cellular retinol-binding protein (CRBP) (14 600 MW) (Bashor et al. 1973; Chytil8z Ong, 1978) for delivery to its site of action within the cell. This complex transport system for retinol is affected (i) by malnutrition, such as protein and zinc deficiencies, (ii) by hormonal changes affecting protein synthesis and metabolism and (iii) by diseases of the intestine, liver and kidney which directly affect either the absorption and metabolism of retinol or the synthesis and metabolism of RBP. The analysis of blood plasma for retinol or RBP or both provides a guideline to the immediate supply of vitamin available but gives no indication as to the extent of reserves within the liver store. Some understanding of the factors influencing or controlling the supply of retinol in plasma is necessary for a sound interpretation of the concentration values for both retinol and RBP which are found in animals undergoing normal growth and development, in order that values outside the expected ranges may be recognized as being abnormal.