Retinyl ester

Vitamin A describes a group of substances (retinol, retinyl esters, and retinal) with defined biological... 

VAN DEN BERG H and VAN VLIET T (1998) Effects of simultaneous, single oral doses of 3-carotene, with lutein or lycopene on the (3-carotene and retinyl ester responses in the triacylglycerol-rich lipoprotein fractions in men. Am J Clin Nutr 68(1) 82-89. 

VAN VLIET T, SCHREURS w H and VAN DEN BERG H (1995) Intestinal beta-carotene absorption and cleavage in men response to beta-carotene and retinyl esters in the triglyceride-rich lipoprotein fi action after a single oral dose of beta-carotene. Am J Clin Nutr 62(1) 110-16. 

In intestinal cells, carotenoids can be incorporated into CMs as intact molecules or metabolized into mainly retinol (or vitamin A), but also in retinoic acid and apoc-arotenals (see below for carotenoid cleavage reactions). These polar metabolites are directly secreted into the blood stream via the portal vein (Figure 3.2.2). Within intestinal cells, retinol can be also esterified into retinyl esters. 

Both intact carotenoids and their apolar metabolites (retinyl esters) are secreted into the lymphatic system associated with CMs. In the blood circulation, CM particles undergo lipolysis, catalyzed by a lipoprotein lipase, resulting in the formation of CM remnants that are quickly taken up by the liver. In the liver, the remnant-associated carotenoid can be either (1) metabolized into vitamin A and other metabolites, (2) stored, (3) secreted with the bile, or (4) repackaged and released with VLDL particles. In the bloodstream, VLDLs are transformed to LDLs, and then HDLs by delipidation and the carotenoids associated with the lipoprotein particles are finally distributed to extrahepatic tissues (Figure 3.2.2). Time-course studies focusing on carotenoid appearances in different lipoprotein fractions after ingestion showed that CM carotenoid levels peak early (4 to 8 hr) whereas LDL and HDL carotenoid levels reach peaks later (16 to 24 hr). 

Tanumihardjo, S. A., H. C. Furr, O. Amedee-Manesme, and J. A. Olson. 1990. Retinyl ester (vitamin A ester) and carotenoid composition in human liver. Int. J. Vitam. Nutr. Res. 60 307-313. 

Vitamin A deficiency affects more than 100 million children around the world (Miller and others 2002) and thus remains an important public health problem in many countries. Vitamin A is essential for vision, reproduction, growth, immune function, and general health of humans (van Lieshout and others 2001). The major sources of vitamin A in the human diet are retinyl esters (preformed vitamin A) found in foods of animal origin and provitamin A carotenoids from fruits and vegetables. Unfortunately, foods containing preformed vitamin A (meat, milk, eggs, etc.) are frequently too expensive for some economically deprived developing countries, and therefore dietary carotenoids are the main source of vitamin A in these countries. 

Mata, N.L., Moghrabi, W.N., Lee, J.S., Bui, T.V., Radu, R.A., Horwitz, I. and Travis, G.H. Rpe65 is a retinyl ester binding protein that presents insoluble substrate to the isomerase in retinal pigment epithelial cells. /. Biol. Chem. 279 635-643, 2004. 

Mercier, M., G. Pascal, and V. Azais-Braesco. 1990. Retinyl ester hydrolase and Vitamin A status in rats treated with 3,3, 4,4 -tetrachlorobiphenyl. Biochim. Biophys. Acta 1047 70-76. 

The overall metabolism of vitamin A in the body is regulated by esterases. Dietary retinyl esters are hydrolyzed enzymatically in the intestinal lumen, and free retinol enters the enterocyte, where it is re-esterified. The resulting esters are then packed into chylomicrons delivered via the lymphatic system to the liver, where they are again hydrolyzed and re-esterified for storage. Prior to mobilization from the liver, the retinyl esters are hydrolyzed, and free retinol is complexed with the retinol-binding protein for secretion from the liver [101]. Different esterases are involved in this sequence. Hydrolysis of dietary retinyl esters in the lumen is catalyzed by pancreatic sterol esterase (steryl-ester acylhydrolase, cholesterol esterase, EC 3.1.1.13) [102], A bile salt independent retinyl-palmitate esterase (EC 3.1.1.21) located in the liver cell plasma hydrolyzes retinyl esters delivered to the liver by chylomicrons. Another neutral retinyl ester hydrolase has been found in the nuclear and cytosolic fractions of liver homogenates. This enzyme is stimulated by bile salts and has properties nearly identical to those observed for... 

E. H. Harrison, Enzymes Catalysing the Hydrolysis of Retinyl Esters , Biochim. Biophys. Acta 1993, 1170, 99-108. 

Hydrolysis of retinyl ester to retinol occurs in the lumen of the small intestine from where it is absorbed with the aid of bile salts, esterified to form retinyl ester and then released into lymph where it is incorporated into chylomicrons. The action of lipoprotein lipase converts chylomicrons to remnants and the retinyl ester remains in the remnants to be taken up by the Uver, where it is stored as the ester until required. On release from the liver, it is transported in blood bound to retinal binding-protein. 

This enzyme [EC 2.3.1.76], also referred to as retinol fatty-acyltransferase, catalyzes the reaction of an acyl-CoA derivative with retinol to generate coenzyme A and the retinyl ester. The CoA derivative can be palmi-toyl-CoA or other long-chain fatty-acyl derivatives of coenzyme A. 

Fio. 35. HPLC record of a standard mixture of retinol and retinyl esters. Conditions column, 10 un octadecyl silica flowrate, I ml/min . mobile phase, (A) CHtOH/58.9 x I0- Af [Ag ], (B) CHsOH/23.5 x lO" W [Ag ], (C) CH,OH detection 330 hm. Peak identity (I) retinol (2) retinyl propionate (3) retinyl linoleate (4) retinyl lauratc (S) retinyl oleate (6) retinyl myristate (7) retinyl palmitate and (8) retinyl stearate. Reprinted with permission from DeRuyter and DeLeenheer (242), Anal. Chem. Copyright 1979 by the American Chemical Society. 

It should be elucidated to what extent the "topical" application of retinyl esters on the respiratory epithelium, especially with BDP, can contribute to the replenishment of the lung stores and thus leading to the improvement of the clinical outcome. 

These results show that retinyl esters in respiratory epithelium and in alveolar cells form a pool of vitamin A, which can be used physiologically by the tissue. The formation of retinol and at least RA from retinyl esters is strictly controlled. So far an unphysiological formation of RA and a subsequent toxicity seems not possible. Retinyl esters, however, are biochemically inert with respect to gene expression or vitamin A activity as long as they are not hydrolyzed. Consequently, the inhalative application, especially in cases of insufficient lung development, could represent a true alternative. The oral contribution is hardly successful because of the poor RBP s)mthesis of the liver and the lack of availability of a parenteral solution is currently not available. 

It is essential to examine whether the uptake of retinyl esters in the respiratory mucosa might be associated with an excess formation of free retinol or RA in the cells with the formation exceeding the binding... 

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