Retinol absorption

Ezetamibe Inhibits Carotenoid and Cholesterol Absorption in Caco-2 Cells but Not Retinol Absorption... 

There are many types of preparations that contain retinol. Absorption is greatest for aqueous preparations, intermediate for emulsions, and slowest for oil solutions. Whereas oil-soluble preparations may lead to greater hepatic storage of the vitamin, water-miscible preparations usually provide higher concentrations in plasma. Vitamin A is available as capsules. Tretinoin (all-trans-retinoic acid Retin A) is available for topical use. Isotretinoin (13-ri.s-retinoic acid Accutane) is available for oral use, as is etretinate (Tegison). 

Retinol formed by retinyl ester hydrolysis (or originating as such in the diet) and dietary -carotene are solubilized in mixed micelles as discussed above, thus enabling these molecules to reach the microvillus membrane. In studies with everted rat gut sacs in vitro, El-Gorab et al. (1975) reported that micellar solutions significantly enhance uptake of both retinol and p-carotene over emulsions. Maximal uptake occurred at the critical micellar concentration of the bile salt mixture. At higher detergent concentrations, 3-carotene uptake declined whereas retinol absorption remained high. 

Although it has been clearly demonstrated that under normal physiological conditions retinol absorption occurs mainly via the lymphatic route (see above Fidge et al., 1968), the existence of an alternative route for retinol absorption has been suggested both by experimental studies in the rat and by features of the genetic disease abetalipoproteinemia in man. Information available suggests that under abnormal conditions retinol may be able to be absorbed via a nonlymphatic pathway and in a biochemical form other than the chylomicron in amounts sufficient to meet nutritional requirements for vitamin A. 

CRBP is distinct from RBP, both immunologically (Ross and Goodman, 1979 Bashor and Chytil, 1975) and by a number of other criteria. It has a lower molecular weight and fails to complex with TTR (Ross and Goodman, 1979 Ong and Chytil, 1978a). CRBP will not bind retinaldehyde, retinoic acid, and retinyl acetate, although these ligands will bind to RBP (Horwitz and Heller, 1974). CRBP has spectroscopic properties that differ from those of RBP. Like free retinol, holo-RBP has a smooth absorption band centered at 330 nm. In CRBP, however, the retinol absorption band is shifted bathochromically to 350... 

Independent Pathways of Retinol and Carotenoid Absorption in Caco-2 Cells ... 

The first study was conducted to determine whether carotenoids and cholesterol share common pathways (transporters) for their intestinal absorption (During et al., 2005). Differentiated Caco-2 cells on membranes were incubated (16 h) with a carotenoid (1 pmol/L) with or without ezetimibe (EZ Zetia, an inhibitor of cholesterol transport), and with or without antibodies against the receptors, cluster determinant 36 (CD36) and scavenger receptor class B, type I (SR-BI). Carotenoid transport in Caco-2 cells (cellular uptake + secretion) was decreased by EZ (lOmg/L) as follows P-C and a-C (50% inhibition) P-cryptoxanthin and LYC (20%) LUT ZEA (1 1) (7%). EZ reduced cholesterol transport by 31%, but not retinol transport. P-Carotene transport was also inhibited by anti-SR-BI, but not by anti-CD36. The inhibitory effects of EZ and anti-SR-BI on P-C transport... 

In systems where several carotenoids are involved, the absorption of each carotenoid is governed by interactions among them carotenoids compete for absorption (Furr and Clark 1997). For example, (3-carotene supplementation reduced absorption of dietary lutein and lycopene in humans (Micozzi and others 1992). Tyssandier and others (2002) found that the absorption of dietary lycopene was reduced when a portion of spinach or pills of lutein were additionally administered to the volunteers. Similarly, the absorption of dietary lutein was reduced by consumption of tomato puree or lycopene pills (Tyssandier and others 2002). Furusho and others (2000) demonstrated that liver retinol accumulation in Wistar rats was significantly reduced when a fixed amount of (3-carotene was replaced by a mixture of (3- and a-carotene, suggesting that each one of these carotenoids mutually inhibits the utilization of the other. The proportion of (3-and a-carotene in the mixture used in that study (Furusho and others 2000) simulated that of carrots. 

Hanberg, A., C.B. Nilsson, C. Trossvik, and H. Hakansson. 1998. Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the lymphatic absorption of a single oral dose of [3H]retinol and on the intestinal retinol esterification in the rat. Jour. Toxicol. Environ. Health 55A 331-344. 

J. Boehnlein, A. Sakr, J. L. Lichtin, R. L. Bronaugh, Characterization of Esterase and Alcohol Dehydrogenase Activity in Skin. Metabolism of Retinyl Palmitate to Retinol (Vitamin A) During Percutaneous Absorption , Pharm. Res. 1994, 11, 1155-1159. 

Vitamin A absorption from the small intestine requires dietary fat and pancreatic lipase to break down retinyl esters and bile salts to promote the uptake of retinol and carotene. Drugs, such as mineral oil, neomycin and cholestyramine, that can modify lipid absorption from the gastrointestinal tract can impair vitamin A absorption. The use of oral contraceptives can signihcantly increase plasma vitamin A levels. 

Absorption, transport, and storage of vitamin A and its derivatives. RBP = retinol-binding protein. 

Since the IU was based on studies that did not take into account the poor absorption and bioavailability of carotenoids in foods, the equivalency of retinol and /3-carotene in the IU system differs from that in the RE system. Thus in the RE system, 1 fig retinol = 6 fig /3-carotene, whereas in the IU system, 1 fig retinol = 2 fig /3-carotene. 

Retinol and its esters exhibit similar UV absorption spectra within a broad wavelength range and have practically equal molar absorptivities when dissolved in a given solvent. The e value of crystalline all-frans-retinol in 2-propanol at the Amax of 325 nm is 52,300 (120), which corresponds to an A m of approximately 1830. The on-column minimum detectable quantity of vitamin A using UV absorption is approximately 2 ng (121). 

The fluorescence excitation spectra of retinol and its esters correspond to their absorption spectra, with wavelength maxima in the 324-328-nm region emission takes place between 470 and 490 nm (Amax of 470 nm) (31). 

R. Blomhoff P. Helgerud, S. Dueland, T. Berg, J. I. Pederson, K. R. Norum, and C. A. Drevon, Lymphatic absorption and transport of retinol and vitamin D-3 from rat intestine—evidence for different pathways, Biochim. Biophys. Acta. 772 109-116 (1984). 

This Chapter will present the actual chromophores of vision, labeled the Rhodonines and derivable from a number of feedstocks, including the retinol family, consist of relatively small molecules with a molecular weight of either 285 (R5 R9) or 299 (R7 R11). They are retinoids of the resonant conjugate type. They are also carboxylic-ion systems and exhibit a negative charge in their fundamental form. The molecules are relatively easily generated in the laboratory in pure form. However, they exhibit a number of unique properties that have made their isolation difficult. They only exhibit the properties of a visual chromophore when in the liquid crystalline state. Their absorption characteristic is a transient one unless a means of de-exciting the molecules of the liquid crystal is present. Finally, they are extremely sensitive to destruction by oxidants and alkali metal ions. 

The Rhodonine chromophores consist of a family of twelve, four related to Retinol (Vitamin A1 and found in saline-based animals), four related to 3,4 dehydroietinol (Vitamin A2 and associated with the freshwater-based animals) and four related to 3-hydroxyretinol (Vitamin A3 and found primarily in the two-winged flies, the Diptera Order of Arthropoda). The functional absorption spectra of these three sets, when in the liquid crystalline state, are virtually identical. This is due to the primary quantum-mechanical mechanism involved and the identical form of their chromophoric structure. The members of each set are spaced at 95 2 nm. 

Based on some early work in the 1930 s, the assumption has been that the chromophores of vision are based on retinol or retinal coupled to a protein, opsin, in such a way as to form a chromophore. The variation in the location and possibly the style of couphng has been assumed to account for the actual spectral absorption of the material. After massive efforts, this premise has still not been demonstrated. However, it has caused a great deal of concentration on retinol and retinal as the fundamental structure of the chromophores. To this day, no laboratory experiments have shown either of these two retinoids exhibit a spectral absorption characteristic matching those of vision, human or otherwise. The retinols are neither chromophores nor analogs of the chromophores of vision. 

This work takes a completely different pathbased on the application of scientific tools unknown before the 1960 s, and still essentially unknown in the biological literature. It also incorporates a set of retinoid molecules into the theory of vision that can be shown to have the required chromophoric properties that Vitamin A aldehyde clearly does not possess. Neither retinol modified by a Schiff base nor further protonation of that Schiff base offers the required absorption spectrum18. 

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