Cis-isomers, of lycopene

Freeze-dried tomato powders obtained from whole tomato fruits and from their pulp after centrifugation, containing 474 and 5399 pg/g dry weight, respectively, were developed for use as additives for food fortification. Cis isomers of lycopene were determined in only a few smdies. The 5-cis-, 9-cis-, and 13-d5 --El5-d5 -lycopene were the isomers found in commercial tomato products. The structures of lycopene cis isomers are shown in Figure 4.2.1 and the structure of the dll-trans isomer is displayed in Figure 6.2.1 in Chapter 6. 

All-trans lycopene is rapidly isomerized to an equilibrium mixture with its cis isomers both in cell culture medium (Liu et al. 2006) and in vivo in prostate tissue (Clinton et al. 1996, van Breemen et al. 2002). The cis isomers of lycopene are absorbed better than the all -trans isomers when fed to humans (Unlu et al. 2007). The 5 -cis isomer predominates in plasma (Gustin et al. 2004). Since lycopene absorption by prostate cells might be due to facilitated diffusion (Liu et al. 2006), it is likely that the cis isomers of lycopene form a significant proportion of intracellular lycopene in the experiments that are reviewed later. 

Boileau TW, Boileau AC, Erdman JW. Bioavailability of all-trans and cis-isomers of lycopene. Exp Biol Med (Maywood) 2002 227 914-919. 

Upon exposure to thermal energy, absorption of light, or involvement in specific chemical reactions, interconversion of lycopene isomers is known to take place. The cis isomers of lycopene, formed by rotation around any of its conjugated double bonds, have chemical and physical characteristics distinctly different from their all-frans counterparts. Some of the differences resulting from trans-to-cis isomerization include lower melting point, decreased color intensity, a shift in the lambda max, smaller extinction coefficients, and the appearance of a new maximum in the ultraviolet spectrum. ... 

Fig. 111.11 Liquid chromatography/mass spectrometry (LC/MS) analysis of isomeric carotenes in a hexane extract from 0.5 ml human serum. Positive ionESI-MS was used on a quadrupole mass spectrometer with selected ion monitoring to record the molecular ions of lycopene, P-carotene, and a-carotene at m/z (mass-to-charge ratio) 536. A C30 HPLC column was used for separation with a gradient from methanol to methyl-tert-butyl ether. The all-trans isomer of lycopene was detected at a retention time of 38.1 min, and various cis isomers of lycopene eluted between 27 min and 39 min. The all-trans isomers of a-carotene and P-carotene were detected at 17.3 min and 19.3 min, respectively [84]...

By use of a Nucleosil 300-5 stationary phase and hexane/N-ethyldiisopro-pylamine (2000 1) as the mobile phase, all-franx, 9-cis, 13-cis, 9,13-dicis, and several other cis isomers of lycopene have been resolved well (178). 

Figure 4. Changes of content of all-tians-and cis-isomers of lycopene during sun-light irradiation...

The presence of other carotenoids can affect the absorption of carotenoids into intestinal mucosal cells, since carotenoids can compete for absorption or facilitate the absorption of another. Data on carotenoid interactions are not clear. Human studies show that /3-carotene decreases lutein absorption, while lutein has either no effect or a lowering effect on /3-carotene absorption. Although not confirmed in humans, the inhibitory effect of lutein on /3-carotene absorption might be partly attributed to the inhibition of the /3-carotene cleavage enzyme by lutein shown in rats. Beta-carotene also seemed to lower absorption of canthaxanthin, whereas canthaxanthin did not inhibit /3-carotene absorption. Studies showed that /3-carotene increased lycopene absorption, although lycopene had no effect on /3-carotene. Alpha-carotene and cryptoxanthin show high serum responses to dietary intake compared to lutein. In addition, cis isomers of lycopene seem to be more bioavailable than the -trans, and selective intestinal absorption of a)X-trans /3-carotene occurs, as well as conversion of the 9-cis isomer to sW-trans /3-carotene. It is clear, then, that selective absorption of carotenoids takes place into the intestinal mucosal cell. 

STAHL w, SCHWARZ w, SUNDQUIST A R and SIES H (1992) Cis-trans isomers of lycopene and beta-carotene in human serum and tissues. Arch Biochem Biophys 294(1) 173-7. 

HPLC is commonly used to separate and quantify carotenoids using C18 and, more efficiently, on C30 stationary phases, which led to superior separations and improved peak shape.32 4046 An isocratic reversed-phase HPLC method for routine analysis of carotenoids was developed using the mobile phase composed of either methanol acetonitrile methylene chloride water (50 30 15 5 v/v/v/v)82 or methanol acetonitrile tetrahydrofuran (75 20 5 v/v/v).45 This method was achieved within 30 minutes, whereas gradient methods for the separation of carotenoids can be more than 60 minutes. Normal-phase HPLC has also been used for carotenoid analyses using P-cyclobond46 and silica stationary phases.94 The reversed-phase methods employing C18 and C30 stationary phases achieved better separation of individual isomers. The di-isomers of lycopene, lutein, and P-carotene are often identified by comparing their spectral characteristic Q ratios and/or the relative retention times of the individual isomers obtained from iodine/heat-isomerized lycopene solutions.16 34 46 70 74 101 However, these methods alone cannot be used for the identification of numerous carotenoids isomers that co-elute (e.g., 13-ds lycopene and 15-cis lycopene). In the case of compounds whose standards are not available, additional techniques such as MS and NMR are required for complete structural elucidation and validation. 

The 5-cis, 9-cis and 15-di-isomers of lycopene have been assayed in various foods and in human tissues using nuclear magnetic resonance (NMR) spectroscopy (Zumbrunn et al., 1985). In the various tomato-based foods surveyed by Schierle et al. (1996), the all-trans isomer represented between 35% to 96% of the total lycopene. In their survey, the proportion of 5-di-isomer in tomato products ranged from 4% to 27%, with considerably lower amounts of the other di-isomers. In human serum and tissues, the di-isomers of lycopene were found to contribute more than 50% of total lycopene (Krinsky et al., 1990). 

In human plasma, lycopene occurs as a 50/50 mixture of cis- and trans-isomers. This is the case in human and animal tissues, because this mixture corresponds to an equilibrium between the trans- and di-isomers (Boileau et al., 1999). Among the different geometrical isomers of lycopene, the dv-isomers (5-cis, 9-cis, 13-cis and 15-di) are better absorbed by the human body than the naturally occurring all-trans form (Stahl and Sies, 1992 Boileau et al., 1999). The m-isomers of lycopene are better absorbed than the all-trans isomer (Sakamoto et al., 1994 Britton, 1995 Stahl and Sies, 1996 Boileau et al., 1999). This may be due to the greater solubility of m-isomers in mixed micelles, possibly to the preferential incorporation into chylomicrons, and a lower tendency of di-isomers to aggregate, f/.v-isomcrs are less likely to crystallize, are more efficiently solubilized in lipophilic solutions and are more readily transported within cells or tissue matrix. 

Hengartner U, Bernhard K and Meyer K (1992) Synthesis, isolation, and NMR-spectroscopic characterization of fourteen (Z)-isomers of lycopene and of some acetylenic didehydro-and tetrahydrolycopenes. Helv Chim Acta 75 1848-1865 Hu Y, Hashimoto H, Moine G, Hengartner U and Koyama Y (1997) Unique properties of the 11 -cis and 11,11 -di-cis isomers of )3-carotene as revealed by electronic absorption, resonance Raman and H and NMR spectroscopy and by HPLC analysis of their thermal isomerization. J Chem Soc Perkin Trans 2 2699-2710... 

Stahl, W., Schwarz, W., Sundquist, A.R., and Sies, H., cis-trans Isomers of lycopene and beta-carotene in human serum and tissues,Hrcfr Biochem. Biophys., 294,173-177,1992. 

Studies with cell-free systems have now confirmed the proposed desaturation of phytoene to the more unsaturated carotenes. Cell-free systems obtained from tomato plastids and spinach chloroplasts will convert [ C]phy-toene (the 15-cis isomer) into lycopene and cyclic carotenes (Kushwaha et al., 1970 Subbarayan et al., 1970), as will an extract from P. blakesleeanus (Davies, 1973). Extracts ofH. cutirubrum (Kushwaha et al., 1976) incorporate radioactivity from tran.s-phytoene into the more unsaturated carotenes. With Flavobacterium extracts [ CJphytoene (the 15-cis isomer) was also converted to the more unsaturated carotenes (Brown et al., 1975). Later studies with tomato plastid extracts have demonstrated the conversion of c/i-[ C]phytofluene, rra/ij-[ C]phytofluene, and /ra/i5- -[ C]carotene to neurosporene and lycopene (Qureshiet al., 1974a,b). Cell-free extracts from H. cutirubrum (Kushwaha et al., 1976) also convert tran -phytofluene to fra/is- -carotene, -carotene to neurosporene, and neurosporene to lycopene. The conversion of neurosporene to lycopene has also been demonstrated using extracts from the Cl 15 mutant of P. blakesleeanus (Davies, 1973). 

The Stereochemistry of Phytoene.—Naturally occurring phytoene has been reported as the 15-cis-isomer of (146) this raises the interesting question as to where in the pathway from phytoene to lycopene does the central double bond revert to the trans-configuration. The recent demonstration that phytoene from Flavobacterium dehydrogenans ° and Mucor hiemalis was... 

Rich Food Sources of Lycopene and Its Cis Isomer Distribution... 

Only 6% of the iifitial total lycopene prepared as a thin film on the surface of each vial remained after 144 hr under fluorescent light (2000 to 3000 lux) at 25°C under N2. Lycopene degradation occurred as a first-order reaction at 2.93 x 10" /min, and the concentration of aU lycopene mono-c isomers already present in the sample, 5-cis-, 9-cis-, l3-cis- and 15-d5 -, showed an inconsistent change in this period. Nevertheless, formation of lycopene di-c isomers was observed after 32 hr of light exposure and when considering relative percentage, loss of 13% of all-trani-lycopene occurred while an increase of 11% for total cis isomers was found after 144 hr. ... 

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