Provitamin structure

It is assumed that in order to have vitamin A activity a molecule must have essentially one-half of its structure similar to that of (i-carotene with an added molecule of water at the end of the lateral polyene chain. Thus, P-carotene is a potent provitamin A to which 100% activity is assigned. An unsubstituted p ring with a Cii polyene chain is the minimum requirement for vitamin A activity. y-Car-otene, a-carotene, P-cryptoxanthin, a-cryptoxanthin, and P-carotene-5,6-epoxide aU have single unsubstimted rings. Recently it has been shown that astaxanthin can be converted to zeaxanthin in trout if the fish has sufficient vitamin A. Vitiated astaxanthin was converted to retinol in strips of duodenum or inverted sacks of trout intestines. Astaxanthin, canthaxanthin, and zeaxanthin can be converted to vitamin A and A2 in guppies. ... 

Tables 4.2.1 and 4.2.2 show, respectively, major sources of P-carotene and other provitamin A carotenoids, especially a-carotene and P-cryptoxanthin. Since cis isomers have different biological and physical-chemical properties than their corresponding dll-trans carotenoids, whenever available, their distribution was included in the tables. The structures of P-carotene cis isomers are shown in Figure 4.2.1, whereas the structures of the other provitamin A carotenoids are presented in Figure...

Higher homologues of glycine have also been evaluated as pro-moieties of active alcohols or phenols. Thus, the highly lipophilic a-tocopherol was de-rivatized with a series of m-aminoalkanecarboxylic acids in the search for a water-soluble, injectable provitamin E [146], Good to high water solubility was indeed achieved. The esters were substrates of liver esterases and showed marked structure-dependent differences in their rate of enzymatic hydrolysis. 

An important function of certain carotenoids is their provitamin A activity. Vitamin A may be considered as having the structure of half of the 3-carotene molecule with a molecule of water added at the end position. In general, all carotenoids containing a single unsubstituted P carotene half have provitamin A activity, but only about half the activity of 3-carotene. Provitamin A compounds are converted to Vitamin A by an oxidative enzyme system present in the intestinal mucosa of animals and humans. This conversion apparendy does not occur in plants (see VITAMINS, VITAMIN a). 

From a nutritional viewpoint, the carotenoids are classified as provitamins and inactive carotenoids. To have vitamin A activity, the carotenoid molecule must incorporate a molecule of retinol, i.e., an unsubstituted /3-ionone ring with an 11-carbon polyene chain. /3-carotene (C40H56, MW = 536.88), the most ubiquitous provitamin A carotenoid, is composed of two molecules of retinol joined tail to tail thus the compound possesses maximal (100%) vitamin A activity. The structures of all other provitamin A carotenoids incorporate one molecule of retinol and hence theoretically contribute 50% of the biological activity of /3-carotene. Among the 600 or so carotenoids that exist in nature, only about 50 possess vitamin A activity in varying degrees of potency. 

Vitamin D is represented by cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2), which are structurally similar secosteroids derived from the UV irradiation of provitamin D sterols. In vertebrates, vitamin D3 is produced in vivo by the action of sunlight on 7-dehydrocholesterol in the skin. Vitamin D2 is produced in plants, fungi, and yeasts by the irradiation of ergosterol. On irradiation, the provitamins are converted to previtamin D, which undergoes thermal transformation to vitamin D. 

Since lycopene lacks the (3-ionic ring structure, unlike (3-carotene, it lacks provitamin A activity. The biological activity of lycopene is thought to be primarily due to its antioxidant properties. However, other mechanisms, such as facilitating gap junction communication (GJC) (Aust et al, 2003 Heber, 2002 Wertz et al, 2004 Zhang et al, 1991, 1992), stimulation of the immune system (Chew and Park, 2004 Heber, 2002 Heber and Lu, 2002 Kim et al, 2004 Wertz et al, 2004), endocrine-mediated pathways... 

The biological activities of carotenoids, such as (3-carotene, are related to their provitamin A activity within the body (Clinton, 1998). Since lycopene lacks the (3-ionic ring structure, it does not have any provitamin A activity (Stahl and Sies, 1996). The biological effects of lycopene in humans have therefore been attributed to mechanisms other than vitamin A. Two major hypotheses have been proposed to explain the anticarcinogenic and antiatherogenic activities of lycopene oxidative and nonoxidative mechanisms. The proposed mechanisms for the role of lycopene in the prevention of chronic diseases are summarized in Figure 6. 

Figure 29-3. Chemical structures of important vitamin A species and the provitamin A carotenoid i-carotene. All-fra/w-fi-carolene (T) is the most important provitamin A carotenoid, which can be converted to all-fraws-retinal and then all-tram-retinol (If), which by definition is vitamin A. All-tram-retinol can be esterified with long-chain fatty acids to form retinyl ester (III), the storage form of vitaminA in the body.The active form of vitamin A in vision is 11-cts-retinal (TV).The transcriptionally active forms of vitaminA are all-tram-retinoic acid (V) and 9-cts-retinoic acid (VI). 13-cA-Retinoic acid (VII) has poor transcriptional regulatory activity but is used clinically as isotretinoin to treat skin diseases.

Figure 9-2 Structural Formulas of Some Provitamins A. (A) P-carotene, and (B) apocarotenal (R = CHO) and apocarotenoic acid ester (R = COOC2H5).

Cycloaddition of 4-phenyl-3//-l,2,4-triazole-3,5(4//)-dione to provitamin D3 affords exclusively the product formed by addition to the least hindered a-face of the more reactive diene, the structure was determined by X-ray8. The diastereoselectivity appears to be determined by the steric effect of the rran.v-hydrindane system, although the mechanism has not been elucidated. The cycloaddition of 4-phenyl-3//-l,2,4-triazole-3,5(4//)-dione was exploited to temporarily protect the diene group in the syntheses of la-hydroxy vitamin D3 7 a(X = H)8,9 and la,25-dihydroxy vitamin D3 7b (X = OH, starting from 25-hydroxy provitamin D3)10. Complete stereocontrol was observed in the cycloreversion step. For related cycloadditions to vitamin D3 see Section 7.2,10.3.4. 

The vitamins D are 9,10-secosteroids, that is, steroid molecules with an opened 9,10 bond of the B-ting. The relationship between the provitamin steroid (perhydro-l,2-cyclopentanophenanthrene ring system) and the 9,10-secosteroid nucleus is shown in structures (5) and (6), cholestane and 9,10-secocholestane (calcitane), respectively. 

A-11 Ergosterol and pro-vitamin D, 7-dehydrocholesterol, in the skin have the same structure except ergosterol has one more double bond in the side chain between C22 and C23 and has one more methyl group at C24. Both the provitamin D and ergosterol are converted to active vitamin D by UV radiation. 

The structure of chlorophylls, carotenoids and anthocyanins present in fruits will be affected to some degree during the development, ripening, and postharvest treatments, with a consequent effect on the colour (quality and quantity) and nutritional value (i.e., carotenoids are a provitamin A source) of the final product. 

Fig. (5). Structures of Vitamin Ai and A2 and some special provitamins A in fish and chicken.

Further products have been identified from the irradiation of 7-dehydro-cholesterol [(130), provitamin D3]. In ether or alcohol the main component of the photolysate was assigned structure (131) which results from the photochemical cyclization of the trans-Z-cis-conformation of the triene (132) formed by ringopening of the cholesterol.92 From reaction in ethanol two alcohol-addition products (133) and (134) have been identified. Two other products of the toxisterol type have been assigned structures (135), the difference between them... 

Cholesterol, with a C27 carbon skeleton (Figure 6.1), is a sterol characteristic for higher animals. It is a steroid that is present in all animal tissues as a major structural component of cellular membranes. It is the precursor of bile acids, provitamin B, and the steroid hormones. Cholesterol can be present in the free form or esterified at the hydroxyl group with fatty acids of various chain length and saturation. Cholesterol also occurs in plants, usually in very small quantities, and marine algae. 

FIGURE 21.3 Structures of P-carotene, zXX-trans retinoic acid, 9-cis retinoic acid, and lycopene. P-Carotene is a provitamin A carotenoid that can undergo central cleavage to form two molecules of retinal. Retinal can undergo further metabolism to form the retinoids, dX -trans retinoic acid and 9-cis retinoic acid, which regulate gene expression via nuclear retinoic acid receptors. Lycopene is a nonprovitamin A carotenoid. 

Work on the stmctural relationships between provitamin D3 (la) and vitamin D3 (7a), and between provitamin D2 (lb) and vitamin D2 (7b) had to await the conclusive determination in 1932 of the structure of the parent compound cholesterol ) Scheme 1). 

Provitamin D (1) and lumisterol (2) can both be transformed into previtamin D (5). Previtamin D may be converted photochemically into provitamin D (1), lumisterol (2), and/or tachysterol (6). Thermally, it may he eonverted into vitamin D (7), even at body temperature. After the isomers had been assigned their correct structures and put in the right places in the isomerization network, it did not take long any more until the individual reaction steps eould be interpreted plausibly. 

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