Carotene retinal from

Retinal] (carotene) Oxidation of Vitamin A (Retinol), in turn derived from pro-vitamin A carotenes PKC... 

Post-ingestion from a-, (3- y-carotene other carotenes from plant leaves a wide variety of fruit, root seed sources e.g. Daucus carota (carrot) (Apiaceae) [root] Retinal covalently linked to opsins (— light receptor Rhodopsins in vision) colour blind John Dalton (atomic theory, 1766-1844) bequeathed his eyes to science 2 centuries on molecular biology confirmed the absence of the gene for the green photoreceptor opsin... 

As you can see from the reaction scheme, the retinal derives from Vitamin A, which requires merely the oxidation of a —CH2OH group to a —CHO group to be converted to retinal. The precursor in the diet that is transformed to Vitamin A is )3-carotene. The )3-carotene is the yellow pigment of carrots and is an example of a family of long-chain polyenes called carotenoids. 

In an analysis of retinal production from cleavage of P-carotene by intestinal homogenates, acetonitrile was simply mixed with the reaction mixture and centrifuged, and an aliquot of the supernatant was injected directly for reversed-phase HPLC analysis (74). 

Figure 1. Formulas of major retinoids and of P-carotene. A, all-tranj retinol B, all-tranj retinal C, all-rran retinoic acid D, 11-cw retinal E, 13-cw retinoic acid F, all-tran retinyl palmtate G, ai -trans retinoyl p-glu-curonide H, the trimethyl methoxyphenol analog of all-rra 5 retinoic acid (etretin, acitretin) I, all-rra 5 p-carotene. From [5], p. 110, reprinted with the permission of the International Life Sciences Institute, Washington DC 20036-4810, Copyright 1996.

Carotene cleavage enzymes — Two pathways have been described for P-carotene conversion to vitamin A (central and eccentric cleavage pathways) and reviewed recently. The major pathway is the central cleavage catalyzed by a cytosolic enzyme, p-carotene 15,15-oxygenase (BCO EC 1.13.1.21 or EC 1.14.99.36), which cleaves p-carotene at its central double bond (15,15 ) to form retinal. Two enzymatic mechanisms have been proposed (1) a dioxygenase reaction (EC 1.13.11.21) that requires O2 and yields a dioxetane as an intermediate and (2) a monooxygenase reaction (EC 1.14.99.36) that requires two oxygen atoms from two different sources (O2 and H2O) and yields an epoxide as an intermediate. ... 

RPE plays numerous functions essential for proper structure and function of retinal photoreceptors. They include the maintenance of the blood-retina barrier, selective uptake and transport of nutrients from the blood to the retina and removal of waste products to the blood, enzymatic cleavage of P-carotene into vitamin A, storage of vitamin A and its metabolic transformations, phagocytosis and molecular renewal of POS, expression and secretion of growth factors and immunomodulatory cytokines (Aizman et al., 2007 Aleman et al., 2001 Crane et al., 2000a,b Elner et al., 2006 Holtkamp et al., 2001 Leuenberger et al., 2001 Lindqvist and Andersson, 2002 Maminishkis et al., 2006 Momma et al., 2003 Strauss, 2005). 

Numerous studies have demonstrated that degradation products of (3-carotene exhibit deleterious effects in cellular systems (Alija et al., 2004, 2006 Hurst et al., 2005 Salerno et al., 2005 Siems et al., 2003). A mixture of (3-carotene degradation products exerts pro-apoptotic effects and cytotoxicity to human neutrophils (Salerno et al., 2005 Siems et al., 2003), and enhances the geno-toxic effects of oxidative stress in primary rat hepatocytes (Alija et al., 2004, 2006), as well as dramatically reduces mitochondrial activity in a human leukaemic cell line, K562, and RPE 28 SV4 cell line derived from stably transformed fetal human retinal pigmented epithelial cells (Hurst et al., 2005). As a result of degradation or enzymatic cleavage of (3-carotene, retinoids are formed, which are powerful modulators of cell proliferation, differentiation, and apoptosis (Blomhoff and Blomhoff, 2006). 

Nagao, A. and J. A. Olson. 1994. Enzymatic formation of 9-cis, 13-cis, and all-fraras retinals from isomers of beta-carotene. Faseb J 8(12) 968-973. 

Napoli, J. L. and K. R. Race. 1988. Biogenesis of retinoic acid from beta-carotene. Differences between the metabolism of beta-carotene and retinal. J Biol Chem 263(33) 17372-17377. 

The enzyme catalyzing the formation of retinal 2 by means of central cleavage of P-carotene 1 has been known to exist in many tissues for quite some time. Only recently, however, the active protein was identified in chicken intestinal mucosa (3) following an improvement of a novel isolation and purification protocol and was cloned in Escherichia coli and BHK cells (4,5). Iron was identified as the only metal ion associated with the (overexpressed) protein in a 1 1 stoichiometry and since a chromophore is absent in the protein heme coordination and/or iron complexation by tyrosine can be excluded. The structure of the catalytic center remains to be elucidated by X-ray crystallography but from the information available it was predicted that the active site contains a mononuclear iron complex presumably consisting of histidine residues. This suggestion has been confirmed by... 

Vitamin A (retinol) is the parent substance of the retinoids, which include retinal and retinoic acid. The retinoids also can be synthesized by cleavage from the provitamin (3-car-otene. Retinoids are found in meat-containing diets, whereas p-carotene occurs in fruits and vegetables (particularly carrots). Retinal is involved in visual processes as the pigment of... 

P-carotene is only one of many antioxidants, which can be detected in the skin. Other carotenoids, for example, lutein and zeaxanthine, are preferentially found in the macula lutea, the so-called yellow spot in the eye. Here, carotenoids are subject to a metabolism typical for that tissue, which cannot be found in other tissues (e.g., formation of meso-zeaxanthine). In addition, they can specifically be absorbed into the macula. In the macula, they protect the retinal pigment epithelial cells against oxidative damage from UV light. Indeed, these two carotenoids can be protective against age-dependent macula degeneration. 

Figure S2.4 shows the structures of 11 -c/.v-retinal and its more stable isomer all-frans-retinal. The reti-nals are related to the alcohol retinol, or vitamin A,. Mammals cannot synthesize these compounds de novo but can form them from dietary carotenoids such as /3-carotene. A deficiency of vitamin A causes night blindness, along with serious deterioration of the eyes and other tissues.

Plants are the major source for dietary provitamin A. As mammals and humans cannot synthesize carotenoids, dietary provitamin A is obtained from plant sources that contain carotenoids having 2,6,6-trimethyl-l-cyclohexen-l-yl rings, such as P-carotene. More than 600 carotenoids have been identified in plants and algae, which together biosynthesize about 0.1 billion tons of carotenoids each year. However, only about ten carotenoids, including P-carotene, are nutritionally significant members of the provitamin A class that can be oxidatively metabolized to retinal in mammals and humans by such organs as the intestine, liver, and kidney and then reduced to retinol. 

Vitamin A is a fat-soluble vitamin involved in critical biological functions, such as embryonic development, growth and vision. It has three primary forms retinol, retinal and retinoic acid. In addition, (3-carotene can be converted to some extent in the body into retinol and is therefore called provitamin A. The bioactivity of these vitamin A compounds varies considerably, ranging from 100% for all-trans retinol, 75% for 13-eis retinol and to just 17% for (3-carotene. All-trans retinol is the major form of vitamin A in milk fat, with values ranging from 8.0 to 12.0 pg/g fat in samples of commercial butter. In contrast, 13-cA retinol is present at a very low... 

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