Retinoic acid structure

Common Name Vitamin A acid retinoic acid Structural Formula ... 

Chemistry. The commercial form cf vitamin A is all-trans retinol, usually formulated as the acetate or palmitate ester. The active forms are the two oxidation products (Fig. 8.1, (l)retinal, which is a structural component of the visual pigment rhodopsin, and (2)retinoic acid, which is required for cell differentiation. There are specific nuclear receptors for retinoic acid. Although the vitamin is marketed in the all-trans form, retinal and retinoic acid are present, in vivo in cis forms. There are also commercial forms related to the retinoic acid structure that have cis stereochemistry. 

Thiinemaim, A. F. and Beyermann, J. 2000. Polyethylenimine complexes with retinoic acid Structure, release profiles, and nanoparticles. Macromolecules 33 6878-85. 

Schapira M, Raaka BM, Samuels HH, Abagyan R. In silica discovery of novel retinoic acid receptor agonist structures. BMC Struct Biol 2001 1 1 (7 pages, www.biomedcentral.com/1472-6807/1/1). 

FIGURE 20.1 Schematic illustration of lycopene metabolic pathway by CM02. (a) 5-cis Lycopene and 13-cis lycopene are preferentially cleaved by CM02 at 9, 10 -double bond. The cleavage product, apo-lO -lycopenal, can be further oxidized to apo-lO -lycopenol or reduced to apo-lO -lycopenoic acid, depending on the presence of NAD+ or NADH. (b) Chemical structures of apo-lO -lycopenoic acid, acyclo-retinoic acid, and all-frans retinoic acid. (Adapted from Hu, K.Q. et al., J. Biol. Chem., 281, 19327, 2006. With permission.)... 

Shimamoto, S., et al. (2007). NMR solution structure of lipocalin-type prostaglandin D synthase Evidence for partial overlapping of catalytic pocket and retinoic acid-binding pocket within the central cavity. /. Biol. Chem. (in press)... 

FIGURE 4.31 Conversion of retinal to retinoic acid mediated by aldehyde dehydrogenase and the structure of disulfiram, an inhibitor of aldehyde dehydrogenase. 

Histochemical studies of bone marrow samples show that peroxidase-containing granules are detectable in promyelocytes. The human promyelo-cytic leukaemia cell line HL-60 grows easily in culture, and the cells resemble promyelocytes both structurally and functionally. Furthermore, they can be induced to differentiate in vitro upon addition of various agents, such as retinoic acid and phorbol esters, and these differentiated cells resemble more mature forms of neutrophils. HL-60 cells possess almost the same amount of myeloperoxidase (4.4 fig per 106 cells) as mature neutrophils, and the enzyme purified from these cells has the same subunit structure. The cells thus actively synthesise the enzyme only until they are induced to differentiate. This cell line has been extensively used to study the molecular events controlling the expression of enzymes such as myeloperoxidase, and also to investigate the molecular controls that lead to a cessation of their expression. 

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. 

Rastinejad, R, Wagner, T., Zhao, Q. and Khorasanizadeh, S. (2000). Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DRl. EMBO J. 19, 1045-1054. 

Attractive alternative to oral retinoid therapy in psoriasis (e.g., etretinate), primarily due to less toxicity. Structural changes to the basic retinoid structure (e.g., conformational rigidity) are claimed to enhance therapeutic efficacy and reduce the local toxicity associated with topical tretinoin (retinoic acid). However, place in therapy should await direct comparisons vs standard regimens in terms of efficacy, toxicity, and cost... 

Fig. 4.6. HRE structure of the RXR heterodimer. Shown is the consensus sequence of the HREs of the RXR heterodimers (see Fig. 4.7) and the different possible arrangements of the hexameric half-site sequences. The hexamers can be arranged palindromically as inverted repeats (a), as everted repeats (b), or as direct repeats (c). n indicates the number of base pairs that lie between the two hexamers. RXR receptor for 9-ds retinoic acid RAR receptor for all-trans retinoic acid T3R receptor for the T3 hormon PPAR peroxisome prohferator-activated receptor VDR receptor for vitamin D3.

Adapalene (Differin) is a derivative of naphthoic acid that resembles retinoic acid in structure and effects. It is applied as a 0.1% gel once daily. Unlike tretinoin, adapalene is photochemically stable and shows little decrease in efficacy when used in combination with benzoyl peroxide. Adapalene is less irritating than tretinoin and is most effective in patients with mild to moderate acnevulgaris. 

Figure 2. General structure of retinoic acid (all trans-retinoic acid). Of the many derivatives tested (e.g., retinol, retinyl acetate), none has the "anti-tumor promoter efficacy, in vivo, as retinoic acid.

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