The major functions of vitamin A are maintenance of normal vision, regulation of cell growth and differentiation, and regulation of lipid metabolism. Vitamin A is a generic name for a group of related fat-soluble compounds that include retinol, retinal, and retinoic acid, which have similar biologic activities. Retinol is the chemical name for vitamin A. It is the transport form and, as retinol ester, also the storage form. A widely used term, retinoids, refers to both natural and synthetic chemicals that are structurally related to vitamin A but may not necessarily have vitamin A activity. Animal-derived foods such as liver, fish, eggs, milk, and butter are important dietary sources of preformed vitamin A. Yellow and leafy green vegetables such as carrots, squash, and spinach supply large amounts of carotenoids, many of which are provitamins that are metabolized to active vitamin A in the body. Carotenoids contribute approximately 30% of the vitamin A in human diets; the most important of these is β-carotene, which is efficiently converted to vitamin A. The recommended dietary allowance for vitamin A is expressed in retinol equivalents, to take into account both preformed vitamin A and β-carotene.
Vitamin A is a fat-soluble vitamin, and its absorption requires bile, pancreatic enzymes, and some level of antioxidant activity in the food. Retinol (generally ingested as retinol ester) and β-carotene are absorbed through the intestinal wall, where β-carotene is converted to retinol (
Fig. 8.18 ). Retinol is then transported in chylomicrons, where it is taken up into liver cells through the apolipoprotein E receptor. More than 90% of the body’s vitamin A reserves are stored in the liver, predominantly in the perisinusoidal stellate (Ito) cells. In healthy persons who consume an adequate diet, these reserves are sufficient to support the body’s needs for at least 6 months. Retinol esters stored in the liver can be mobilized; before release, retinol binds to a specific retinol-binding protein (RBP), synthesized in the liver. The uptake of retinol and RBP in peripheral tissues is dependent on cell surface RBP receptors. After uptake by cells, retinol is released, and the RBP is recycled back into the blood. Retinol may be stored in peripheral tissues as retinyl ester or may be oxidized to form retinoic acid.
Function. In humans, the best-defined functions of vitamin A are the following: • Maintaining normal vision in reduced light. The visual process involves four forms of vitamin A–containing pigments: rhodopsin, located in rod cells, the most light-sensitive pigment and therefore important in reduced light; and three iodopsins, located in cone cells, each responsive to a specific color in bright light. The synthesis of rhodopsin from retinol involves (1) oxidation to all-trans-retinal, (2) isomerization to 11-cis-retinal, and (3) interaction with opsin to form rhodopsin. A photon of light causes the isomerization of 11-cis-retinal to alltrans-retinal, and a sequence of configuration changes (preformed vitamin A) (carotenes, pro-vitamin A)
Fig. 8.18 Vitamin A metabolism.
in rhodopsin, which produce a visual signal. In the process, a nerve impulse is generated (by changes in membrane potential) and transmitted by means of neurons from the retina to the brain. During dark adaptation, some of the all-trans-retinal is reconverted to 11-cis-retinal, but most is reduced to retinol and lost to the retina, explaining the need for a continuous supply of retinol.