Retinol ionone ring

A small but variable proportion of the carotenoids with one or two P-ionone rings (mainly P-carotene) are cleaved in the enterocytes to produce retinol (vitamin A). This process is very tightly controlled, so that too much vitamin A is not produced, although the control mechanism is not clear. Some cleavage of P-carotene can also occur in the liver, but this does not account for the turnover of P-carotene in the body. Small amounts of carotenoids are subject to enterohepatic circulation, but this does not account for losses. 

Vitamin A (retinol, 6.1) is the parent of a range of compounds known as retinoids, which possess the biological activity of vitamin A. In general, animal foods provide preformed vitamin A as retinyl esters (e.g. 6.5, which are easily hydrolysed in the gastrointestinal tract) while plant foods provide precursors of vitamin A, i.e. carotenoids. Only carotenoids with a /3-ionone ring (e.g. /1-carotene) can serve as vitamin A precursors. /3-Carotene (6.6)... 

Retinol A primary alcohol containing a p-ionone ring with an unsaturated side chain, retinol is found in animal tissues as a retinyl ester with long-chain fatty acids. 

The parent vitamin A compound, retinol, has the empirical formula C2oH3oO and a molecular weight (MW) of 286.44. The molecule comprises a cyclohexenyl (/3-ionone) ring attached at the carbon-6 (C-6) position to a polyene side chain whose four double bonds give rise to cis-trans (geometric) isomerism. The predominant isomer, all-trans-retinol (Fig. 1), possesses maximal (100%) vitamin A activity and is frequently accompanied in natural foodstuffs by smaller amounts of 13-ds-retinol, which exhibits 75% relative activity in the rat (6). Other cis isomers of retinol also occur in nature, but they are of low potency, and their contribution to the total vita-... 

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 A retinol (P-ionone ring) marine based and marine derived animals Rhodonine,()... 

Vitamin A is found in nature and is available in several forms. Retinol (vitamin A) is an unsaturated alcohol containing an ionone ring and can be obtained from fish liver oil (Table 13-2), egg yolk, milk, and butter. Vitamin A2 (dehydroretinol) is present in freshwater fishes. /3-carotene, a carotenoid, is the most important precursor of this vitamin. 

Structurally, vitamin A and many synthetic retinoids consist of a (3-ionone ring, a polyunsaturated polyene chain, and a polar end group. The polar end group can exist in several oxidation states, as retinol, retinal, or retinoic acid. Retinol and retinyl esters are the most abundant vitamin A forms found in the body (Blaner and Olson, 1994). Retinol can be esterified with long-chain fatty acids (mainly palmitate, oleate, and stearate) to form retinyl esters, which are the body s storage form of vitamin A. Retinol also can undergo oxidation to retinal, which can be oxidized further to retinoic acid. The active... 

RBP is relatively rich in aromatic amino acids, which create a deep hydrophobic pocket that is specific for the 8-ionone ring, polyene side chain, and polar end group. In addition to all- trans-retinol, RBP binds retinaldehyde, retinoic acid, and 13-c/s-retinol, but not retinyl esters or carotene. RBP shows considerable structural homology with 8-lactoglobulin from milk and other... 

Nutritioncdly, on the basis of whether or not they have an unsubstituted /8-ionone ring and can therefore act as precursors of retinol (the provitcunin A cMotenoids)... 

Fig. 14. The recognition motifs in the iLBPs. The amino acids are numbered according to their location in crystalline ALBP, but corresponding amino acids present in the other crystalline proteins are also listed. Two locations for fatty acids can be seen, one where fatty acid is bound to ALBP, P2, MFB2, and HFABP the other where IFABP binds fatty acids. The position of bound retinol in CRBP and CRBPII is also shown, although because the /3-ionone ring is edge-on, it is not readily distinguished from a fatty acid. Note that the polar residues can be either ionizable or polar (Arg or Gin and Tyr). Further details of structural factors in the three motifs are given in the text.

The other interesting polar interaction involves Lys-40. The positive charge on the side chain of Lys-40 appears to interact with the isoprene tail of the retinol, with the NZ atom located above the plane of the conjugated 7r-electron field. The /3-ionone ring is located in a hydrophobic environment formed by the two helices and /3C-j8D and /3E-j8F turns. Eight water molecules were also identified in the cavity. All of them make hydrogen bonds to internal polar side chains or water molecules. 

The crystal structure of CRBPll is closest to that of CRBP. The Ca positions agree within 0.7 A, as is apparent in Table II. Unlike bound retinol in CRBP, the dihedral angle between the plane of the jS-ionone ring and the chain is not an ideal cis or trans (Winter et al., 1993). In the report of the crystal structure, the complementarity between the bound retinol and protein was examined and appeared fairly good (Winter a/., 1993). In the holo protein, within the cavity there are five empty spaces that are not occupied by retinol atoms. Most of these subcavities contain water molecules, which appear to be an integral part of the protein structure because they occupy similar positions in the apo structure. 

Fig. 13.10. Superposition of retinol, retinal, and retinoic acid in the conformations adopted at the active site of RBP, and in various small molecule crystal structures. For clarity, the H atoms have been omitted. TVvo distinct conformations are observed for the single bond between the )8-ionone ring and the isoprene chromophore. The synclinal conformation, adopted at the receptor site, corresponds to the global energy minimum of the isolated molecule...

Fig. 13.11. Binding of retinol to the active site of retinol binding protein (IRBP, stereo-diagram). The ligand is completely encapsulated in the protein with the y -ionone ring in the center and the unsaturated isoprene chromophore stretching to the solvent surface along the main axis of the fi barrel packing motif in this protein...

A group of compounds described as vitamin A (retinol) includes those that, within their molecules, possess the characteristic (3-ionone ring and the isoprene chain. They are capable of forming molecules of polyene alcohol, aldehyde, acid, and ester (retinal, retinoic acid, and retinyl palmitate, respectively) (Figure 7.1). They can occur in many isomeric forms as groups of compounds possessing diversified prop-... 

Chemical structure (Figure 1). Molecules formally composed of four isoprene units they naturally occur as an alcohol (retinol), an aldehyde (retinal), or as an acid (retinoic acid). From each of the three basic forms two variants exist vitamin A, with a jS-ionone ring and vitamin A2 with a dehydrated S-ionone ring. Native retinoids show cis-trans isomerism of the double bonds. Carotenoids are proforms of vitamin A (Figure 2). 

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