Retinoids biosynthesis

The objectives of this chapter are to describe (l)retinoids that are currently in clinical use, including the adverse effects associated with the therapeutic use of these compounds (2) retinoid biosynthesis and metabolism (3) the basis of action of retinoids in molecular, cellular, and organismal contexts including vision and (4) new agents on the horizon of retinoid biology. 

Retinoids. Biosynthesis is included in a general review on vitamin A. The cis-trans isomerization of retinals by crude tissue extracts has been achieved/ After oral administration of the synthetic retinoid (187) to human subjects some eighteen metabolites were isolated from the urine and faeces, almost all having a shortened polyene chain/ °... 

An example of gene expression can be illustrated by consideration of the action of steroid hormones, and in the control of sterol biosynthesis. Steroid hormones enter the cell by diffusion through the plasma membrane and bind to their steroid hormone receptor. These receptors are part of a large related family that includes those for glucocorticoids, oestrogens, androgens, thyroid hormone, calcitriol and the retinoids. All steroid hormone receptors are zinc finger transcription factors. The receptor must ... 

Inhibition of dihydroceramide desaturase. The last enzyme in the de novo biosynthesis of ceramide is inhibited by GT-11, but at high concentrations this compound also inhibited SIP lyase and SPTase (147, 148). Fenretinide (4-HPR, Fig. 12) also inhibited dihydroceramide desaturase (147, 148). This synthetic retinoid and its analogs have apoptogenic activity, which elevates intracellular ceramide levels and induces cell death in a variety of cell types in vitro and in vivo by multiple mechanisms (117, 149, 150). 

Napoli, J.L. Retinoid binding-proteins redirect retinoid metabolism biosynthesis and metabolism of retinoic acid. Semin. Cell Dev. Biol. 8 403-415, 1997. 

Retinoic acid appears to regulate the activity, transport, storage, and metabolism of members of the vitamin A family by binding to and/or activating RAREs present in genes encoding retinoid-binding proteins or enzymes involved in RA biosynthesis. For example, a mechanism exists for... 

Another set of reactions involving retinol that has been studied in liver concerns the formation of retinyl phosphate and of retinyl phosphomannose conjugates. These studies have been directed toward the hypothesis that retinoid-containing glycolipids serve as intermediates for specific glycosylation reactions. It is well established that the biosynthesis of some glycoproteins is markedly decreased in a number of tissues in retinoid deficiency, and that glycoprotein... 

The biosynthesis and regeneration of these photosensitive pigments requires that retinaldehyde (or a retinoid precursor) is provided to the membranes in which they are sequestered. The delivery of retinoids to these membranes, which are generally found in specialized photoreceptor cells, has been investigated in some vertebrates. In these animals, proteins called retinoid-binding proteins serve as vehicles that transport retinoids in the serum, cell sap, and interstitial space of the eye. The critical role of these proteins in the normal functioning of the vertebrate visual system is one of the major topics of this chapter. 

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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