Retinoic acid biological function

Vitamin A (retinol) and retinoic acid are carotenoid oxidation compounds that are very important for human health. The main functions of retinoids relate to vision and cellular differentiation. With the exception of retinoids, it was only about 10 years ago that other carotenoid oxidation products were first thought to possibly exert biological effects in humans and were implicated in the prevention - or promotion of degenerative diseases. A review on this subject was recently published. ... 

Here we have another simple chemical transformation, the oxidation of the aldehyde group in retinal to the carboxyl group of retinoic acid. Although the chemical change is simple, the physiology is profoundly different. Retinoic acid has nothing to do with vision but a lot to do with development and differentiation. Here we have yet another example of the sensitive interdependence of chemical structure and biological function. 

Retinoic Acid Receptor. Most of the biological effects of retinoids are mediated through the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). Both all-/ran.s-retinoic acid and 9-d.v-rctinoic acid serve as agonists of RAR, while only 9-d.v-rctinoic acid functions as an agonist of RXR. The functional RAR exists as a heterodimer with RXR, while functional RXR exists as a homodimer. Methoprene is a juvenile hormone III analogue that mimics the activity of this insect hormone. 

Vitamin A is a fat-soluble vitamin involved in critical biological functions, such as embryonic development, growth and vision. It has three primary forms retinol, retinal and retinoic acid. In addition, (3-carotene can be converted to some extent in the body into retinol and is therefore called provitamin A. The bioactivity of these vitamin A compounds varies considerably, ranging from 100% for all-trans retinol, 75% for 13-eis retinol and to just 17% for (3-carotene. All-trans retinol is the major form of vitamin A in milk fat, with values ranging from 8.0 to 12.0 pg/g fat in samples of commercial butter. In contrast, 13-cA retinol is present at a very low... 

Delva L, Bastie JN, Rochette-Egly C, Kraiba R, Balitrand N, Despouy G, Chambon P, and Chomienne C (1999) Physical and functional interactions between cellular retinoic acid binding protein II and the retinoic acid-dependent nuclear complex. Molecular and Cell Biology 19,7158-67. 

Re.seaa-h since the mid-1980s has taken va.si strides in determining the molecular mechanism of action of vitamin A. It appears that the vitamin exerts its biological function with respect to development, diffcrcnlialion. and metabolism like a steroid hormone. The biologically active species is believed to be retinoic acid. Two intracellular retinoic acid-binding proteins have been isolated. CRABP(I) and CRABPfll). The.se appear to have functions similar to those of the CRBPs. 

Retinoic acid is involved in only two of the known functions of Vitamin A, namely growth and cellular differentiation. Retinoic acid is a potent inducer of cellular differentiation, in vitro (17-191. and may be necessary for normal gene expression (17.271. Several nuclear transcription factors for retinoic acid have been identified (28.291 and the associated genes products may be necessary to prevent cellular transformation. Therefore, retinoic acid may be necessary for homeostasis. However, because of its potency, it exists in low concentrations in biological systems. 

The function of certain carotenoids as provitamins A (retinol (13), 3,4-didehydroretinol (14) and retinal (18)), treated in the previous section, is during the last two decades further expanded as precursor role for additional biologically important retinoids, namely the all-trans and 9-cis isomers of retinoic acid (19), Fig. 6. Their function in growth regulation, development and cell differentiation via specific nuclear receptors are being clarified [24,31], The origin of all-trans and 9-cis retinoic acid (19) has been considered [29,32,33],... 

DHA-inserted phospholipids themselves have been receiving attention for their boosting effects on cell differentiators such as retinoic acid and dibutyryl cyclic adenosine monophosphate (2,3). For this reason, we intended to encapsulate a biological response modifier (BRM) in DHA-insert phospholipid liposomes, expecting that the DHA-inserted phospholipid bilayer of the liposomes might enhance the function of the BRM. 

The existence of biologically active metabolites of retinoic acid has been reported. Krishnamurthy et al. (1963) detected a fat-soluble metabolite of retinoic acid, which displayed biological activity in a rat curative assay, in the liver of chicks administered a 10-mg oral dose of the parent retinoid. Similarly, Wolf et al. (1963) reported that an intestinal metabolite, isolated from retinoid-deficient rats injected with labeled retinoic acid, was active in restoring to normal levels the mucopolysaccharide biosynthesis in retinoid-deficient rat intestinal cell-free particle suspensions. The same laboratory also described a decarboxy-lated metabolite of both retinol and retinoic acid that was isolated from the intestine of retinoid-deficient rats administered retinol or retinoic acid. This compound, which appeared to have both carboxyl and hydroxyl functional groups, was biologically active in a growth assay (Yagishita et al., 1964). In... 

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