Carotenoid retinal

Special tasks. Some lipids have adopted special roles in the body. Steroids, eicosanoids, and some metabolites of phospholipids have signaling functions. They serve as hormones, mediators, and second messengers (see p.370). Other lipids form anchors to attach proteins to membranes (see p.214). The lipids also produce cofactors for enzymatic reactions—e.g., vitamin K (see p.52) and ubiquinone (see p.l04). The carotenoid retinal, a light-sensitive lipid, is of central importance in the process of vision (see p.358). 

Photosynthetic bacteria are found both among the eubacteria and the archaebac-teria. Those found among the eubacteria all contain (B)Chl, while those found among the archaebacteria, i.e. the halobacteria, contain the carotenoid retinal, but no (B)Chl. 

Figure 6.6 Two photosynthetic pigments chlorophyll (npper diagram), and the hR retinyhdene chro-mophore, which consists of a carotenoid, retinal, hnked to a Schiff-base, itself linked to a lysozyme residue of bR (29-31). Retinal is in its all-trans conformation in the intermediate diagram, and in its 13-cw conformation in the lower diagram. Conventional atom numbering of retinal is shown.

Because of the presence of an extended polyene chain, the chemical and physical properties of the retinoids and carotenoids are dominated by this feature. Vitamin A and related substances are yellow compounds which are unstable in the presence of oxygen and light. This decay can be accelerated by heat and trace metals. Retinol is stable to base but is subject to acid-cataly2ed dehydration in the presence of dilute acids to yield anhydrovitamin A [1224-18-8] (16). Retro-vitamin A [16729-22-9] (17) is obtained by treatment of retinol in the presence of concentrated hydrobromic acid. In the case of retinoic acid and retinal, reisomerization is possible after conversion to appropriate derivatives such as the acid chloride or the hydroquinone adduct. Table 1 Hsts the physical properties of -carotene [7235-40-7] and vitamin A. 

In nature, vitamin A aldehyde is produced by the oxidative cleavage of P-carotene by 15,15 - P-carotene dioxygenase. Alternatively, retinal is produced by oxidative cleavage of P-carotene to P-apo-S -carotenal followed by cleavage at the 15,15 -double bond to vitamin A aldehyde (47). Carotenoid biosynthesis and fermentation have been extensively studied both ia academic as well as ia iadustrial laboratories. On the commercial side, the focus of these iavestigations has been to iacrease fermentation titers by both classical and recombinant means. 

Some 117 naturally occurring apo-carotenoids, 88 of which have been fully identified and another 6 naturally occurring seco-carotenoids have been referenced as carotenoids, thus representing around 15% of the carotenoids numbered to date (see Figure 3.3.1). This subfamily of carotenoids would be even larger if we consider the retinoids andnorisoprenoids. However, these compounds are excluded by nomenclature rules that dictate that they are not deemed to be carotenoids because of the absence of two central methyl groups (at C20 and C20 ). Retinoic acid, retinal. 

Several recent studies on trienes,(70,71) vitamin A, retinal, and higher carotenoids<72-76) have been published however, much work remains to be done in this area. 

The recognition of the importance of MP in maintaining the health of the retina has led to the development of a number of methods for determining its concentration in situ. These methods, necessarily noninvasive, are routinely employed in dietary supplementation studies with lutein or zeaxanthin to monitor the uptake of the carotenoids into the retina. Every method exploits the optical properties of lutein and zeaxanthin, specifically their absorbance at visible wavelengths. The detection of a light signal, modified by the carotenoids, is accomplished either by the retinal photoreceptors themselves (psychophysical methods) or by a physical detector such as a photomultiplier,... 

Also, we have noted that patients with unilateral cataracts after trauma or retinal detachment repair typically have very similar RRS carotenoid levels in the normal and in the pseudophakic eye. Thus, we have concluded that there is a decline of macular carotenoids that reaches a low steady state just at the time when the incidence and prevalence of AMD begins to rise dramatically. While this age effect has been noticed sometimes also in other studies using clinical populations and different MP detection methods (Sharifzadeh et al. 2006, Nolan et al. 2007), several groups have reported constant, age-independent MP levels. Examples include reflectance-based population studies in which respective average MP optical densities of 0.23 (Delori et al. 2001), 0.33 (Berendschot et al. 2002), and 0.48 (Berendschot and Van Norren 2004) were determined. 

The oxidation of P-carotene with potassium permanganate was described in a dichloromethane/ water reaction mixture (Rodriguez and Rodriguez-Amaya 2007). After 12 h, 20% of the carotenoid was still present. The products of the reaction were identified as apocarotenals (apo-8 - to apo-15-carotenal = retinal), semi-P-carotenone, monoepoxides, and hydroxy-p-carotene-5,8-epoxide. 

Lutein and zeaxanthin are the dominant carotenoids in nonretinal eye tissue, and lycopene and p-carotene have been found in the ciliary body, which after the retina and the retinal pigment epithelium (RPE) contains the highest quantity of carotenoids (Bernstein et al. 2001). The orbital adipose tissue also contains measurable quantities of lutein and p-carotene, and possibly other carotenoids as minor constituents (Sires et al. 2001). It is also interesting to note that lutein was recently identified in the vitreous body of human fetuses, 15-28 weeks old (Yakovleva et al. 2007). However, these results may have to be considered with caution, because the vitreous bodies were described as substantially being penetrated with hyaloid blood vessels, which could have contaminated the vitreous with blood. 

Moreover, carotenoids may quench electronically excited states and scavenge free radicals formed in the retina, and therefore protect biomolecules from oxidative damage. Due to the low energy level of the first excited triplet state ( Car), carotenoids (Car) can act as efficient acceptors of triplet state energy from photosensitizers (S) (Equation 15.1), such as all-tra .s-retinal, the photosensitizers of lipofuscin (Rozanowska et al., 1998), or singlet oxygen C02) (Equation 15.2) (Cantrell et al., 2003) ... 

Interestingly, carotenoids more abundant in the blood plasma than zeaxanthin, such as lycopene, P-carotene, and P-cryptoxanthin, do not accumulate in the retina. RPE cells express p,p-carotene 15,15 -monooxygenase (BCO), formerly known as P-carotene 15,l5 -dioxygcnase, an enzyme that catalyzes the oxidative cleavage of P-carotene into two molecules of all-trans-retinal (Aleman et al., 2001 Bhatti et al., 2003 Chichili et al., 2005 Leuenberger et al., 2001 Lindqvist and Andersson, 2002). Therefore it may be suggested that p -carotene transported into RPE-cells is efficiently cleaved into retinal molecules. BCO cleaves also P-cryptoxanthin (Lindqvist and Andersson, 2002), and its absence in the retina may also be explained by its efficient cleavage to retinoids. However, lycopene, often the most abundant carotenoid in human plasma, cannot serve as a substrate for BCO, and yet it is not detectable in the neural retina (Khachik et al., 2002). 

The greatest concentration of the macular pigment is present in the avascular part of the retina. This suggests that the RPE may play the predominant role in uptake and transport of xanthophylls to the photoreceptors. Moreover, about 25% of the total retinal xanthophylls are present in the POS (Rapp et al., 2000 Sommerburg et al., 1999), which, under normal conditions, are intimately associated with the RPE. This proximity lends further support to the hypothesis of a role for the RPE in the selective uptake of carotenoids into the retina. 

FIGURE 15.3 Hypothetical pathways responsible for carotenoid uptake, metabolic transformations, tran-scytosis to the neural retin, or secretion to the blood. 

It has been shown in many studies that protective effects of carotenoids can be observed only at small carotenoid concentrations, whereas at high concentrations carotenoids exert pro-oxidant effects via propagation of free radical damage (Chucair et al., 2007 Lowe et al., 1999 Palozza, 1998, 2001 Young and Lowe, 2001). For example, supplementation of rat retinal photoreceptors with small concentrations of lutein and zeaxanthin reduces apoptosis in photoreceptors, preserves mitochondrial potential, and prevents cytochrome c release from mitochondria subjected to oxidative stress induced by paraquat or hydrogen peroxide (Chucair et al., 2007). However, this protective effect has been observed only at low concentrations of xanthophylls, of 0.14 and 0.17 pM for lutein and zeaxanthin, respectively. Higher concentrations of carotenoids have led to deleterious effects (Chucair et al., 2007). 

Bernstein, PS, Balashov, NA, Tsong, ED, and Rando, RR, 1997. Retinal tubulin binds macular carotenoids. Invest Ophthalmol Vis Sci 38, 167-175. 

Kalariya, NM, Ramana, KV, Srivastava, SK, and van Kuijk, FJ, 2008. Carotenoid derived aldehydes-induced oxidative stress causes apoptotic cell death in human retinal pigment epithelial cells. Exp Eye Res 86, 70-80. 

Kanofsky, JR and Sima, PD, 2006. Synthetic carotenoid derivatives prevent photosensitised killing of retinal pigment epithelial cells more effectively than lutein. Exp Eye Res 82, 907-914. 

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