Retinol functions

Biological, spectroscopic, and chromatographic methods have been used to assay vitamin A and the carotenoids. Biological methods have traditionally been based on the growth response of vitamin A—deficient rats. The utiUty and shortcomings of this test have been reviewed (52,53). This test has found apphcabiUty for analogues of retinol (54,55). Carotenoids that function as provitamin A precursors can also be assayed by this test (56). 

The carotenoids are the most widely distributed group of pigments, occur naturally in large quantities, and are known for their structural diversity and various functions. The carotenoids constitnte a widespread class of natural pigments that occur in all three domains of life in the eubacteria, the archea, and the eucarya. Carotenoids are ubiquitous organic molecules, but they are not produced by the human body. They have been fonnd to be essential to human health based on the nutritional understanding of vitamin A (retinol) and (i-carotene. ... 

Vitamin A (retinol) and retinoic acid are carotenoid oxidation compounds that are very important for human health. The main functions of retinoids relate to vision and cellular differentiation. With the exception of retinoids, it was only about 10 years ago that other carotenoid oxidation products were first thought to possibly exert biological effects in humans and were implicated in the prevention - or promotion of degenerative diseases. A review on this subject was recently published. ... 

The other major class of extracellular LBPs of mammals is the lipocalins (Flower, 1996). These are approximately 20 kDa, P-sheet-rich proteins, performing functions such as the transport of retinol in plasma or milk, the capture of odorants in olfaction, invertebrate coloration, dispersal of pheromones, and solubilizing the lipids in tears (Flower, 1996). The retinol-binding protein (RBP) of human plasma is found in association with a larger protein, transthyretin, the complex being larger than the kidney threshold and thus not excreted, although the RBP itself may dissociate from the complex to interact with cell surface receptors in the delivery of retinol (Papiz et al., 1986 Sundaram et al., 1998). 

The failure of proteins to fold into their functional forms can occasionally lead to "misfolding" or "conformational" diseases.140 Many of these diseases are associated with the formation of amyloid protein, an insoluble material that is deposited as fibrils or plaques in different tissues and organs of the body. They include amyloid Ap protein as the major constituent of the plaques in Alzheimer patients, PrPc associated with neuro-degenerative diseases, a-synuclein (AS) associated with Parkinson s diseases, transthyretin (TTR) as a homotetrameric protein that is involved in the transport of thyroid hormones and retinol in human serum. In particular, the Ap protein is a peptide of 39-43 amino acids that is the... 

Carotenoids are isoprenoid compounds that are biosynthesized only by plants and microorganisms. Some carotenoids (a- and p-carotene, p-cryptoxanthine) can be cleaved into vitamin A (retinol) by an enzyme in the small intestine. Carotenoids have been reported to present some effects in the prevention of cardiovascular diseases [410] and in the prevention of some kind of cancers [411]. Furthermore, antioxidant activity has been widely reported [411-414] but a switch to pro-oxidant activity can occur as a function of oxygen concentration [415,416]. 

Vitamin A, or retinol, is essential for the proper maintenance of the functional and structural integrity of epithelial cells, and it plays a major role in epithelial dif-... 

Since alcohol dehydrogenase is required for the conversion of retinol to retinal, excessive and prolonged ethanol ingestion can impair the physiological function of vitamin A. The decreased conversion of retinol to retinal results from competitive use of the enzyme by ethanol. Night blindness may result, since the visual cycle is a retinol-dependent physiological process. 

Vitamin A (retinol, retinal, retinoic acid—the three active forms of vitamin A, and p-carotene) function in the maintenance of reproduction, vision, promotion of growth, differen tiation and maintenance of epithelial tissues, and gene expression. A deficiency of vitamin A results in impotence, night blindness, retardation of growth, and xerophthalmia. Large amounts of vitamin A are toxic and can result in an increased incidence of frac tures. 

Do we know all of the special chemistry of vitamin A that is involved in its functions Retinal could form Schiff bases with protein groups as it does in the visual pigments. Redox reactions could occur. Conjugative elimination of water from retinol to form anhydroretinol is catalyzed nonenzymatically by HC1. Anhydroretinol occurs in nature and... 

Figure B3.6.11 The binding of retinol to p-lactoglobutin that has been denatured by exposure to high pressure. The sample contaiining 270 pM p-lactoglobulin was pressurized to 400 MPa for 15 min. After release of pressure, retinol in ethanol was added and fluorescence was measured as a function of time. Parameters final protein concentration 8.5 pM in 20 mM phosphate buffer . ex = 330 nm k9m = 470 nm. Circles, native p-lactoglobulin triangles, pressurized p-lactoglobulin. Reprinted from Ikeuchi et al. (2001) with permission from the American Chemical Society.

Vitamin Vitamin A [retinol] RDA/AI Men 900 pg/d Women 700 pg/d Physiological function Required for normal vision, gene expression, reproduction, embryonic development, and immune function Adverse Effects of Excessive Consumption Teratological effects liver toxicity... 

Retinoic acid (vitamin A acid), in which the alcohol group has been oxidized, shares some but not all of the actions of retinol. Retinoic acid is ineffective in restoring visual or reproductive function in certain species in which retinol is effective. Flowever, retinoic acid is very potent in promoting growth and controlling differentiation and maintenance of epithelial tissue in vitamin A-deficient animals. Indeed, all-trans-retinoic acid (tretinoin) appears to be the active form of vitamin A in all tissues except the retina, and is 10- to 100-fold more potent than retinol in various systems in vitro. Isomerization of this compound in the body yields 13-n.v-rctinoic acid (isotretinoin), which is nearly as potent as tretinoin in many of its actions on epithelial tissues but may be as much as fivefold less potent in producing the toxic symptoms of hypervitaminosis A. 

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