Retinol vitamin retinyl esters

In food, vitamin A exits in two forms preformed vitamin A (retinol and retinyl esters) in animal products and pro-vitamin A carotenoids... 

Structurally, vitamin A and many synthetic retinoids consist of a (3-ionone ring, a polyunsaturated polyene chain, and a polar end group. The polar end group can exist in several oxidation states, as retinol, retinal, or retinoic acid. Retinol and retinyl esters are the most abundant vitamin A forms found in the body (Blaner and Olson, 1994). Retinol can be esterified with long-chain fatty acids (mainly palmitate, oleate, and stearate) to form retinyl esters, which are the body s storage form of vitamin A. Retinol also can undergo oxidation to retinal, which can be oxidized further to retinoic acid. The active... 

As the intake of vitamin A increases, there is an increase in the excretion of metabolites in bile, once adequate liver reserves have been established. However, the biliary excretion of retinol metabolites reaches a plateau at relatively low levels, and it seems likely that this explains the relatively low toxic threshold (Olson, 1986). Vitamin A intoxication is associated with the appearance of both retinol and retinyl esters bound to albumin and in plasma lipoproteins, which can be taken up by tissues in an uncontrolled manner the amount of circulating retinol bound to RBP does not increase. Retinol has a membrane lytic action it was noted in Section 2.2.2.3 that one of the functions of RBP binding seems to be to protect tissues against retinol, as well as to protect retinol against oxidation (Meeks et al., 1981). 

Retinoids are essential to fish and other vertebrates. Predators acquire them in the diet, either as retinol or retinyl esters they may also be acquired through the conversion of dietary carotenoids produced by plants (Fig. 2). In fish, carotenoids may be metabolized to retinol (vitamin Aj) or didehydroretinol (vitamin A2) (Fig. 1). For example, fish can convert canthaxanthin to /3-carotene47, which is a dimer of retinal that is readily converted to retinol (Figs. 1 and 2). Didehydroretinol (Fig. 1) is formed... 

FIG. 6. Compartmental model proposed by Green et al. (1993) for liver and whole-body vitamin A metabolism. Compartment 11 is plasma retinol. PC, parenchymal cells NPC, nonparenchymal cells (assumed here to be perisinusoidal stellate cells) ROH, retinol RE, retinyl esters CM, chylomicrons. 

Vitamin A is present in foods as retinol and retinyl esters (usually retinyl acetate or retinyl palmitate). Retinoids are often employed as food additives... 

UV absorbance detection has been most widely used for vitamin A analysis. However, because retinol and retinyl esters are highly fluorescent, detection limits of one order of magnitude better than in assays with UV detection can be obtained using fluorescence detection. Also, electrochemical detection is a valuable alternative to UV and fluorescence detection provided the eluent contains water to incorporate essential electrolytes. Another detector for LC is the mass spectrometer. The LC-MS approach has also been applied to the analysis of vitamin A and its metabolites. 

Zinc deficiency accompanied by a depression in plasma retinol has been noted in several studies. Some investigators have reported an increased liver vitamin A in several species of zinc-deficient animals (Stevenson and Earle, 1956 Saraswat and Arora, 1972 J. C. Smith et aL, 1973, 1976 Brown et aL, 1976 Jacobs et al., 1978 Carney et aL, 1976). There are also reports in humans in an association between lowered zinc, retinol, and RBP (Jacobs et a/., 1978 Solomons and Russell, 1980). J. C. Smith et al, (1973) suggested that hepatic mobilization of vitamin A was impaired by zinc deficiency and their follow-up studies demonstrated a depression in liver and plasma RBP in the zinc-deficient rat compared to pair-fed controls (Brown et al., 1976 Smith et al., 1974). The depression was hypothesized to be the result of a depressed synthesis rather than an increased turnover of RBP. That preformed RBP is present in zinc-deficient rats was demonstrated by Carney et al. (1976) using labeled vitamin A. Zinc-deficient rats, whether or not they were also vitamin A-deficient, were able to mobilize over a short time span a small oral dose of vitamin A as well as could their pair-fed controls. Those animals deficient only in zinc excreted metabolites of the labeled vitamin in a similar quantitative manner as the pair-fed controls for 6 days postdosing. These data suggest that the release of retinol from retinyl ester stores, as well as a depressed RBP synthetic rate, contributed to low plasma levels of vitamin A in zinc deficiency. 

Eckhoff C, Collins MD, Nau H (1991) Human plasma sll-trans, 13-cis- and 13-d5-4-oxoretinoic acid profiles during subchronic vitamin A supplementation Comparison to retinol and retinyl ester plasma levels. J Nutr 121 1016-1025... 

Because many factors affect the assimilation of carotenoids from foods (Figure 2), conversion factors need to be considered. This is especially important when most sources of vitamin A are from provitamin A carotenoids in the population. Bioavailability of preformed vitamin A, i.e., retinol and retinyl esters, is not a major concern because 80-95% of them are absorbed. However, foods that are high in preformed retinol (liver, eggs, and fortified milk) are not necessarily consumed by everybody. When discussing carotenoids from food, four terms need to be defined (see Table 1) ... 

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

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. 

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... 

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. 

This class includes both vitamin A and the provitamin A carotenoids. All the compounds related to all-trani-retinol (Figure 19.11) are known as vitamin A. These compounds, together with their metabolites and synthetic derivatives, exhibiting the same properties are called retinoids. Vitamin A is found in animal products as retinyl esters (mainly palmitate). 

In the body retinol can also be made from the vitamin precursor carotene. Vegetables like carrots, broccoli, spinach and sweet potatoes are rich sources of carotene. Conversion to retinol can take place in the intestine after which retinyl esters are formed by esterifying retinol to long chain fats. These are then absorbed into chylomicrons. Some of the absorbed vitamin A is transported by chylomicrons to extra-hepatic tissues but most goes to the liver where the vitamin is stored as retinyl palmitate in stellate cells. Vitamin A is released from the liver coupled to the retinol-binding protein in plasma. 

---