Retinal 7£ ,9£ ,13£ -retinol vitamin

Vitamin Ai (retinol) is derived in mammals by oxidative metabolism of plant-derived dietary carotenoids in the liver, especially -carotene. Green vegetables and rich plant sources such as carrots help to provide us with adequate levels. Oxidative cleavage of the central double bond of -carotene provides two molecules of the aldehyde retinal, which is subsequently reduced to the alcohol retinol. Vitamin Ai is also found in a number of foodstuffs of animal origin, especially eggs and dairy products. Some structurally related compounds, including retinal, are also included in the A group of vitamins. 

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. 

The retinoids, a family of molecules that are related to retinol (vitamin A), are essential for vision, reproduction, growth, and maintenance of epithelial tissues. Retinoic acid, derived from oxidation of dietary retinol, mediates most of the actions of the retinoids, except for vision, which depends on retinal, the aldehyde derivative of retinol. 

Reproduction Retinol and retinal are essential for normal repno duction, supporting spermatogenesis in the male and preventing fetal resorption in the female. Retinoic acid is inactive in maintain ing reproduction and in the visual cycle, but promotes growth and differentiation of epithelial cells thus, animals given vitamin A only as retinoic acid from birth are blind and sterile. 

The leveisal of the oxidative pathway of vitamin A (retinol —r retinal —>-retinoic add) does not occur in the body, When retinoic acid is feci to animals, even in relatively large doses, there is no storage and, in fact, die molecule is rapidly metabolized and cannot be found several hours after administration. The metabolic products have not been fully identified. Several fractions from liver or intestine, isolated after administering retinoic add marked with carbon-14, have been shown to have biological activity. 

Vitamin A or a precursor must be provided in the diet. This vitamin occurs in various forms (vitamers) retinol (alcohol), retinal (aldehyde), retinoic acid and vitamin A palmitate (ester). Requirements for vitamin A are usually expressed in international units (IU) per kg of diet. The international standards for... 

In the intestinal mucosal cells, /3-carotene is cleaved via an oxygenase (an enzyme that introduces molecular 02 into organic compounds) to frans-retinal (aldehyde form of trans-retinol, as shown in Table 6.2), which in turn is reduced to frans-retinol, vitamin Av Retinol is then esterified with a fatty acid, becomes incorporated into chylomicrons, and eventually enters the liver, where it is stored in the ester form until it is required elsewhere in the organism. The ester is then hydrolyzed, and vitamin Ax is transported to its target tissue bound to retinol-binding protein (RBP). Since RBP has a molecular weight of only 20,000 and would be easily cleared by the kidneys, it is associated in the bloodstream with another plasma protein, prealbumin. 

Retinoic acid is a metabolic product of vitamin A that supports the growth and differentiation of epithelial tissues. Retinoic acid is formed in the cytosol by the reversible oxidation of retinol to retinal, and the irreversible oxidation of retinal to retinoic acid. There is controversy as to whether retinal is oxidized by retinal dehydrogenase, which is linked to NAD+, or by retinal oxidase. 

Bone and Teeth Defective formation of enamel of teeth. Abnormal bone and tooth formation are reversed by vitamin A administration. Carbohydrate metabolism Vitamin A helps glucose synthesis from triose molecules. Reproduction Retinol and retinal are essential for normal reproduction. 

Generally, vitamin A serves three classes of functions (1) support of the differentiation of epithelial cells, (2) support of the viability of the reproductive system (fetal growth and vitality of the testes), and (3) utilization in the visual cycle. Dietary retinoic acid can support only the first function. Animals raised on diets containing retinoic acid as the only source of vitamin lose their ability to see in dim light and become sterile. In males, sperm production ceases. In females, fetuses are resorbed. Retinoic acid cannot be stored in the liver, as it lacks the hydroxyl group needed for attachment of the fatty acid. Retinyl esters, retinol, and retinal are interconvertible. Retinal can be oxidized to form retinoic acid. All three functions of vitamin A can be supported by dietary retinyl esters, retinol, or retinal. Although these forms can be converted to retinoic acid, retinoic acid apparently cannot be reduced to form retinal. These relationships are summarized in Figure 9.44. 

Retinal (vitamin A aldehyde), Retinoic acid (vitamin A acid). Retinol (vitamin A alcohol) see entries in Chapter 6. 

There are different physiological forms known as vitamins A, namely retinol (vitamin Aj) and esters, 3-dehydroretinol (vitamin A2) and esters, retinal (retinene, vitamin A aldehyde), 3-dehydroretinal (retine-2), retinoic acid, neovitamin A, and neo-b-vitamin Aj. There are active anologs and related compounds known as vitamins A, namely a-, f -, and y-carotene, neo-/3-carotene B, cryptoxanthine, myxoxanthine, torularhodin, aphanidn, and echinenone [3]. Vitamin A is susceptible to oxidation and degradation. Therefore, the control of the vitamin A level is recommended. 

Fat malabsorption, particularly caused by celiac disease or chronic pancreatitis, and protein-energy malnutrition predispose to vitamin A deficiency. Liver disease diminishes RBP synthesis, and ethanol abuse leads both to hepatic injury and to a competition with retinol for alcohol dehydrogenase, which is necessary for the oxidation of retinol to retinal and retinoic acid. Vitamin A deficiency may lead to anemia, though the precise mechanism is not known. ... 

Retinoids are essential to fish and other vertebrates. Predators acquire them in the diet, either as retinol or retinyl esters they may also be acquired through the conversion of dietary carotenoids produced by plants (Fig. 2). In fish, carotenoids may be metabolized to retinol (vitamin Aj) or didehydroretinol (vitamin A2) (Fig. 1). For example, fish can convert canthaxanthin to /3-carotene47, which is a dimer of retinal that is readily converted to retinol (Figs. 1 and 2). Didehydroretinol (Fig. 1) is formed... 

Chemical structure of a -tmns retinol (vitamin Ai), the most active form of vitamin A. Oxidation of C15 to an aldehyde or an acid produces, respectively, retinaldehyde (retinal) and retinoic acid. The cis-trans isomerization of the double bond between Ci i and C12 occurs during functioning of retinaldehyde in vision. 

A route to canthaxanthin using Wittig reaction methodology has been described (ref. 50). In this approach retinol (vitamin A) was oxidised in dichloromethane with manganese dioxide to retinal (vitamin A aldehyde) which was converted to 4-acetoxyretinal by bromination with N-bromosuccinimide in dichloromethane containing acetic acid. By reaction with retinyltriphenylphosphonium hydrogensulphate derived by reaction of triphenylphosphine with retinol hydrogensulphate, isocryptoxanthin acetate was obtained. Treatment of this with 68% hydrobromic acid formed... 

Vitamin A is the isoprenoid alcohol retinol, which is required for a number of body processes including vision, growth, maintenance of mucous membranes, reproduction and proper growth of the cartilage matrix upon which bone is deposited. Of these, the molecular basis of its role in the visual cycle is best understood. In addition to the alcohol retinol, both retinal and retinoic acid (Fig. 2.4) also act to restore some of the deficiency symptoms. In rod vision, retinol is oxidised to retinal. 11-ds-Retinal combines with the protein opsin to form rhodopsin. After the absorption of a photon, rhodopsin undergoes a series of changes, eventually dissociating to opsin and all-fraMS-retinal. This last compound is converted back to 11-ds-retinal by retinal isomerase (EC.5.2.1.3) Retinoic acid is able to replace retinol in all functions except the visual cycle and reproduction. 

C uv, ( 455,520 nm. /S-C. is the most abundant carotene in the animal and plant kingdoms. It was first isolated by Wackenroder in 1826 from carrots (Dau-cus carota, Apiaceae). Willstatter determined the molecular formula in 1907 and Karrer the constitutional formula in the early 1930 s. fi-C. is the provitamin A, which is oxidatively cleaved in animals to yield 2 molecules of retinal and subsequently reduced to retinol (vitamin A) (see pigments of vision). 

Vitamin A is a generic term that includes preformed vitamin A , namely retinol (alcohol), retinal (aldehyde) and retinoic acid (carboxylic acid) , and the provitamin A carotenoids, which are those carotenoids capable of metabolism to retinol, e.g. 3-carotene (Fig. 51.1). 

From above results, it suggests that retinoids such as retinal (16), retinol (vitamin A, 18) and retinoic acid (20), and carotenoids such as P-carotene (2), P-cryptoxanthin (5) and lycopene (3) could regulate the expression of P,P-carotene 15,15 -monooxygenase using a transcriptional feedback mechanism through their interaction with the members of the retinoic acid (20) receptor (RAR) family (Figure 5) [11]. 

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