Vitamin A (Beta
Carotene) is necessary for growth & repair of bodytissues. This fat soluble vitamin helpsto maintain
smooth, soft disease-free skin. It helps to protect the mucousmembranes of the mouth, nose, throat, and lungs; thus reducing susceptibilityto respiratory infections. It protects against night-blindness. Vitamin A aids in bone and teeth development.Pro vitamin A (beta
carotene) has been shown to reduce the risk of lung cancerand certain oral cancers. Unlike Vitamin A, Beta Carotene is non-toxic. VitaminA consists of three biologically active molecules, retinol,
retinal(retinaldehyde) and retinoic acid. Each of these compounds is derived from theplant precursor molecule, beta-carotene(a member of a family of molecules known as carotenoids). Beta-carotene, which consists of two molecules ofretinal linked at their aldehyde ends, is also referred to as the provitaminform of vitamin A. Ingested beta-carotene is cleaved in the lumen of theintestine by the enzyme, beta -carotene dioxygenase to yield retinal. Retinalis reduced to retinol by the enzyme, retinaldehyde reductase, an NADPHrequiring enzyme within the intestines. Retinol is esterified to form palmiticacid (a fatty acid), and delivered to the blood via chylomicrons. The uptake ofchylomicron remnants by the liver results in delivery of retinol to this organfor storage as a lipid ester within lipocytes. Transport of retinol from theliver to extrahepatic tissues occurs by binding of hydrolyzed retinol to apo-retinol binding protein (RBP). Theretinol-RBP complex is then transported to the cell surface within the Golgiapparatus and secreted. Within extrahepatic tissues, retinol is bound to cellular retinol binding protein (CRBP).Plasma transport of retinoic acid is accomplished by binding to albumin. Within cells, both retinol and retinoic acid bind to specific receptorproteins. Following binding, the receptor-vitamin complex interacts withspecific sequences in several genes involved in growth and differentiation andaffects expression of these genes. In this capacity retinol and retinoic acidare considered hormones of the steroid/thyroid hormone superfamily of proteins.Vitamin D also acts in a similar capacity. Several genes whose patterns ofexpression are altered by retinoic acid are involved in the earliest processesof embryogenesis including the differentiation of the three germ layers, organogenesisand limb development. Photoreception in the eye is the function of two specialized cell typeslocated in the retina; the rod and cone cells. Both rod and cone cells containa photoreceptor pigment in their membranes. The photosensitive compound of mostmammalian eyes is a protein called opsinto which is covalently coupled an aldehyde of vitamin A. The opsin of rod cellsis called scotopsin. Thephotoreceptor of rod cells is specifically called rhodopsin or visual purple.This compound is a complex between scotopsin and the 11-cis-retinal(also called 11-cis-retinene) form of vitamin A. Rhodopsin is aserpentine receptor imbedded in the membrane of the rod cell. Coupling of 11-cis-retinaloccurs at three of the transmembrane domains of rhodopsin. Intracellularly,rhodopsin is coupled to a specific G-protein called transducin. When therhodopsin is exposed to light it is bleachedreleasing the 11-cis-retinal from opsin. Absorption of photons by 11-cis-retinaltriggers a series of conformational changes on the way to conversion all-trans-retinal. Oneimportant conformational intermediate is metarhodopsin II. The release of opsin results in a conformationalchange in the photoreceptor. This conformational change activates transducin,leading to an increased GTP-binding by the a-subunit of transducin. Binding ofGTP releases the beta-subunit from the inhibitory beta- and beta-subunits. TheGTP-activated beta-subunit in turn activates an associated phosphodiesterase;an enzyme that hydrolyzes cyclic-GMP (cGMP) to GMP. Cyclic GMP is required tomaintain the Na+ channels of the rod cell in the open conformation.The drop in cGMP concentration results in complete closure of the Na+channels. Metarhodopsin II appears to be responsible for initiating the closureof the channels. The closing of the channels leads to hyperpolarization of therod cell with concomitant propagation of nerve impulses tothe brain. Vitamin A is stored in the liver and deficiency of the vitamin occursonly after prolonged lack of dietary intake. The earliest symptoms of vitamin Adeficiency are night blindness.Additional early symptoms include follicular hyperkeratinosis, increasedsusceptibility to infection and cancer and anemia equivalent to iron deficientanemia. Prolonged lack of vitamin A leads to deterioration of the eye tissuethrough progressive keratinization of the cornea, a condition known asxerophthalmia. An increased risk of cancer in vitamin deficiency is thought tobe the result of depletion in beta-carotene. Beta-carotene is a very effectiveantioxidant and is suspected to reduce the risk of cancers known to beinitiated by the production of free radicals. Of particular interest is thepotential benefit of increased beta-carotene intake to reduce the risk of lungcancer in smokers. However, caution needs to be taken when increasing theintake of any of the lipid soluble vitamins. Excess accumulation of vitamin Ain the liver can lead to toxicity which manifests as bone pain,hepatosplenomegaly, nausea and diarrhea.