Lycopene transport

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). 

In the enterocyte, provitamin A carotenoids are immediately converted to vitamin A esters. Carotenoids, vitamin A esters, and other lipophilic compounds are packaged into chylomicrons, which are secreted into lymph and then into the bloodstream. Chylomicrons are attacked by endothelial lipoprotein lipases in the bloodstream, leading to chylomicron remnants, which are taken up by the liver (van den Berg and others 2000). Carotenoids are exported from liver to various tissues by lipoproteins. Carotenes (such as (3-carotene and lycopene) are transported by low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL), whereas xanthophylls (such as lutein, zeax-anthin, and (3-cryptoxanthin) are transported by high-density lipoproteins (HDL) and LDL (Furr and Clark 1997). 

Most of the organs (thyroid, spleen, kidney, liver, pancreas, and heart) investigated appear similar in that lycopene and P-carotene are the predominant carotenoids found in these organs, with an approximately equal percentage distribution between them. Selectively, the cellular uptake of individual carotenoids may be based upon the selective transport of the individual carotenoids. 

Following the absorption of lycopene, it is transported to various organs and accumulates in tissues. Tissue distribution of lycopene varies considerably suggesting unique biological effects on some tissues and not on others. The highest concentrations of lycopene are in the testes, adrenal glands, liver, and prostate. Table VI shows the lycopene levels in human tissues (Rao and Agarwal, 1999). 

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. 

Lycopene, like other carotenoids, is transported in plasma exclusively by lipoproteins, primarily in LDL particles [22, 27, 28], and the isomeric pattern reflects that of the blood. Li et al. [29] employed surface enhanced Raman spectroscopy to demonstrate that both... 

Holloway DE, Yang M, Paganga G, Rice-Evans CA, Bramley PM. Isomerization of dietary lycopene during assimilation and transport in plasma. Free Radic Res 2000 32 93-102. 

Another complicating factor in the intestinal mucosal cell is the partial conversion of provitamin A carotenoids (/3- and a-carotenes and cryptoxanthin) to vitamin A (primarily to retinyl esters). Therefore, in absorption studies these metabolic reactions must be accounted for in measuring intestinal transport. Nonprovitamin A carotenoids such as lycopene, lutein, and zeaxanthin are incorporated intact, although some cleavage can occur. Earlier studies on rats indicated that lycopene and /3-carotene are absorbed by passive diffusion. However, recent evidence from the kinetics of /3-carotene transport through Caco-2 cell... 

Once absorbed, passively from lipid micelles by the enterocyte, lycopene enters the portal lymphatics and thence the liver, from which it enters the peripheral bloodstream, mainly in association with the /3-lipoproteins, in which it is transported to the peripheral tissues. Its half-life in plasma is of the order of 12-33 days longer than that of /3-carotene, which is less than 12 days. Clearly, many of these factors are interdependent, and there is a need for further clarification of the key independent determinants of lycopene status, and whether plasma levels can provide an adequate picture of tissue and whole body status. 

Patients with alcoholic cirrhosis of the liver have greatly reduced hepatic lycopene concentrations indeed, hepatic lycopene seems to offer a sensitive index of hepatic health. Studies of organ concentrations (Table 3), suggest a gradient from circulating levels in plasma to different ones in specific tissues. The different carotenoid ratios between organs (not shown) also indicate selective transport and accumulation. However, the mechanisms involved are poorly understood. No lycopene is detectable in the retina or lens of the eye, where lutein and zeax-anthin are found however, lycopene is present in the ciliary body. 

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