Liver retinol

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. 

Retinyl esters and the P-carotene are incorporated into chylomicrons and taken up mainly by hepatocytes. In the liver retinol may be stored in stellate cells as retinyl esters, oxidized to retinoic acid or liberated into cells bound to retinol-binding proteins (RBP). All E retinoic acid and its 9Z isomer have an affinity for nuclear receptors. They activate the transcription and bind as dimers to specific nucleotide sequences, present in promoters of target genes. 

Transport to the liver Retinol esters present in the diet are hydrolyzed in the intestinal mucosa, releasing retinol and free fatty acids (Figure 28.19). Retinol derived from esters and from the cleavage and reduction of carotenes is reesterified to long-chain fatty acids in the intestinal mucosa and secreted as a component of chylomicrons into the lymphatic system (see Figure 28.19). Retinol esters contained in chylomicrons are taken up by, and stored in, the liver. 

Wolf G (2001) Retinoic acid homeostasis retinoic acid regulates liver retinol esterification as well as its own catabolic oxidation in liver. Nutrition Reviews 59,391. ... 

A second liver retinol (retinyl ester) compartment was added to the model for reasons analogous to those for adding a second liver /3-carotene compartment. The experimental observations show an initial rise and fall in plasma retinol-d4 concentration, then a sustained plasma retinol-d4 level for —16 days after ingesting /3-carotene-dg (Fig. 4). Prior to adding the second liver retinol compartment, the model predicted that almost all... 

The fast turnover liver -carotene-dg curve exhibits a narrow peak after ingestion of the experimental dose, and it is similar to the predicted fast turnover liver retinoid-d4 curve. The slow turnover liver /8-carotene-dg peak is broader than the fast turnover liver /3-carotene-dg peak and decays to near zero in approximately 50 days after ingestion of the labeled dose. Notice that the slow turnover liver -carotene-dg level does not remain elevated as long as the slow turnover liver retinol-d4. The slow turnover liver /3-carotene decays in a fashion similar to the slow turnover liver /3-carotene-dg, as expected, since the /3-carotene-dg is the source of the elevated slow turnover liver /3-carotene. 

Under conditions of either insufficient or excessive dietary retinoid intake an individual s circulating level of retinol is defended irrespective of the abundance of liver retinol stores, until liver stores reach some critical level beyond which the amount of circulating RBP-ROH is affected [35, 42, 52]. The regulatory factors responsible for establishing and maintaining this homeostatic set point within an individual are not well understood. In addition to any individual s normal serum retinol homeostatic set point, the critical level of hepatic stores also varies from one individual to another, and it has been suggested that it is influenced by non-retinoid factors such as the protein quality and quantity of the diet [34-36, 47, 53]. 

The first example is the plasma-borne retinol-binding protein, RBP, which is a single polypeptide chain of 182 amino acid residues. This protein is responsible for transporting the lipid alcohol vitamin A (retinol) from its storage site in the liver to the various vitamin-A-dependent tissues. It is a disposable package in the sense that each RBP molecule transports only a single retinol molecule and is then degraded. 

Retinoids are alcohols and accordingly soluble in ethanol, isopropanol, and polyethylenglycol. Major sources of natural retinoids are animal fats, fish liver oil (retinylesters) and yellow and green vegetables (carotenoids). Ingested retinylesters (RE) are hydrolyzed to retinol by enteral hydrolases in the intestine. ROL and carotenoids are absorbed by intestinal mucosa cells. 

Ethanol also inhibits ADH-catalyzed retinol oxidation in vitro, and ethanol treatment of mouse embtyos has been demonstrated to reduce endogenous RA levels. The inhibition of cytosolic RolDH activity and stimulation of microsomal RolDH activity could explain ethanol-mediated vitamin A depletion, separate from ADH isoenzymes. Although the exact mechanism of inhibition of retinoid metabolism by ethanol is unclear, these observations are consistent with the finding that patients with alcoholic liver disease have depletedhepatic vitamin A reserves [review see [2]. 

A small but variable proportion of the carotenoids with one or two P-ionone rings (mainly P-carotene) are cleaved in the enterocytes to produce retinol (vitamin A). This process is very tightly controlled, so that too much vitamin A is not produced, although the control mechanism is not clear. Some cleavage of P-carotene can also occur in the liver, but this does not account for the turnover of P-carotene in the body. Small amounts of carotenoids are subject to enterohepatic circulation, but this does not account for losses. 

Retinol and retinyl Liver Common eider No Increased Wayland et al. 

Carotene (all-trans), (3-cryptoxanthin (all-trans and -cis), zeaxanthin (all-trans), luteoxanthin isomers, violaxanthin (all-trans and -cis), and neoxanthin (all-trans and -cis) were identified in several mango cultivars (Mercadante and others 1997 Ornelas-Paz and others 2007, 2008). Mango retinol was found to be highly bioavail-able by estimating vitamin A and carotene reserves in the liver and plasma of rats. Information on the tocopherol content in mango is very scarce, but it seems to be low (Burns and others 2003 Ornelas-Paz and others 2007). 

After cell uptake, provitamin A carotenoids are readily bioconverted to retinal by intestinal cells, although some bioconversion of carotenoids can take place in the liver (West and Castenmiller 1998). The retinal can be reversibly reduced to retinol or... 

While the human body can remove an excess of any water-soluble vitamin, excesses of fat-soluble vitamins are more serious. Early arctic explorers discovered that the Inuit regarded seal liver and polar bear liver as taboo and must not be eaten. Those explorers who ignored this advice risked retinol poisoning as the livers of both these species are rich in retinol (vitamin A) that can not be excreted. The effects of retinol poisoning are extremely unpleasant. It is for this reason that fortification with fat-soluble vitamins is not likely to be undertaken. 

Ah-responsive and Ah-nonresponsive strains females, age 10 weeks given single ip injection of 50 mg/kg BW killed after 7 days Both groups had increased body weight, increased blood EROD activity, decreased plasma retinol levels, and increased plasma total thyroid hormone levels. The Ah-responsive group also had increased hepatic pentoxyresorufin-O-deethylase activity, increased livercytochrome P-450 activity, and increased liver weight 12... 

T.W. Knight and A.F. Death, Effects of oral and injected vitamin A (retinol) supplements on liver vitamin A and plasma carotenoid and cholesterol concentrations in cattle. Animal Sci. 69 (1999) 607-612. 

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... 

Vitamin A (retinol) Animal tissue, liver, green plants Component of the pigment involved in vision... 

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. 

Vitamin Ai (retinol) is derived in mammals by oxidative metabolism of plant-derived dietary carotenoids in the liver, especially -carotene. Green vegetables and rich plant sources such as carrots help to provide us with adequate levels. Oxidative cleavage of the central double bond of -carotene provides two molecules of the aldehyde retinal, which is subsequently reduced to the alcohol retinol. Vitamin Ai is also found in a number of foodstuffs of animal origin, especially eggs and dairy products. Some structurally related compounds, including retinal, are also included in the A group of vitamins. 

Storage. The liver not only stores energy reserves and nutrients for the body, but also certain mineral substances, trace elements, and vitamins, including iron, retinol, and vitamins A, D, K, folic acid, and Bi2. 

Repeatedly it was shown that the semm retinol level and RBP level in prematures are significantly lower than that of neonates (Shah and Rajalekshmi, 1984). In the liver of prematures, significantly lower retinol levels can be foimd in comparison to neonates (Shensi et ah, 1985). Plasma values lower than 20 gg/dl are not rare in this case and they should be taken as an indicator of a relative vitamin A deficit. But a moderate vitamin A deficiency is not only a problem of countries with poor or inadequate food sources. 

Recently we published data that even in countries with excellent food sources and availability, insufficient vitamin A supply will occur (Schulz et ah, 2007). The aim of this trial was to analyze vitamin A and p-carotene status and investigate the contribution of nutrition to vitamin A and p-carotene supply in mother-infant pairs of multiparous births or births within short birth rates. Twenty-nine volimteers aged between 21 and 36 years were evaluated for 48 hours after delivery. In order to establish overall supply, retinol and p-carotene were determined in maternal plasma, cord blood, and colostrum via HPLC analysis. A food frequency protocol was obtained from all participants. Regardless of the high-to-moderate socioeconomic background, 27.6% of participants showed plasma retinol levels below 1.4 pmol/liter, which can be taken as borderline deficiency. In addition, 46.4% showed retinol intake <66% of RDA and 50.0% did not consume liver at all, although liver contributes as a main source for preformed retinol. Despite a high total carotenoid intake of 6.9 3.9mg/day, 20.7% of mothers showed plasma levels <0.5 pmol/liter p-carotene. 

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. 

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