Retinoic add

Gruber JR, Ohno S, and Niles RM (1992) Increased expression of protein kinase C alpha plays a key role in retinoic add-induced melanoma differentiation. J Biol Chem 267 13356-13360... 

Mark M, Ghyselinck NB, Chambon P (2009) Function of retinoic add receptors during embryonic development. Nucl Recept Signal 7 e002... 

Receptor fiir 9-ds retinoic acid, RXR 9-cis retinoic add. Terpenoids AGGTCA DR-1... 

Fig. 4.11. Principle of signal transduction by RXR heterodimers. The activated hormone can be made available to the RXR heterodimer in three different ways, a) The hormone (e.g. T3 hormone) is synthesized in endocrinal tissue and reaches the DNA-bound RXR-T3R heterodimer in the nucleus via passive transport, b) The active hormone is formed in the cytosol from an inactive apo-hormone (as for, e.g. 9-ds-retinoic add), c) The hormone is synthesized intracellularly. In aU three cases, the binding of the hormone-RXR-heterodimeric complex is the signal that induces transcription activation of the downstream genes. After Mangelsdorf and Evans, 1995.

RenaudJ. E, Rochel, N., Ruff, M., Vivat, V., Chambon, P, Gronemeyer, H. and Moras,D., Crystal structure of the RAR- hgand-binding domain bound to all-trans retinoic add (1995) Nature 378, 681-689... 

The leveisal of the oxidative pathway of vitamin A (retinol —r retinal —>-retinoic add) does not occur in the body, When retinoic acid is feci to animals, even in relatively large doses, there is no storage and, in fact, die molecule is rapidly metabolized and cannot be found several hours after administration. The metabolic products have not been fully identified. Several fractions from liver or intestine, isolated after administering retinoic add marked with carbon-14, have been shown to have biological activity. 

Retinoid acids (RAs), the active retinoid derivatives of vitamin A, regulate complex gene networks. The pleiotropic effects of active retinoids are transduced by their cognate nuclear receptors, retinoid X receptors (RXRs) and retinoic add receptors... 

Figure 2.1. Major physiologically active retinoids. Relative molecular masses (Mr) retinol, 286.5 retinaldehyde, 284.4 retinoic acid, 300.4 13,14-dihydroxy-retinol, 318.5 4-oxoretinol, 301.5 retroretinol, 286.5 14-hydroxy-retroretinol, 302.5 anhydroretinol, 269.6 4-oxo-retinoic add, 315.4 4-hydroxyretinoic acid, 316.4 dehydroretinol, 284.4 retinyl acetate, 328.5 and retinyl pahnitate, 524.9. 

Crowe DL (1993) Retinoic add mediates post-transcriptional regulation of keratin 19 mRNA levels. Journal of CeUSdence 106,183-8. 

Duester G (2000) Families of retinoid dehydrogenases regulating vitamin A function production of visual pigment and retinoic add. European Journal of Biochemistry 267,4315-24. 

Zolfaghari R and Ross AC (2000) Lecithin retinol acyltransferase from mouse and rat Uver. cDNA cloning and liver-specific regulation by dietary vitamin A and retinoic add. Journal of Lipid Research 41,2024-34. 

Nadin, L Murray, M. Participation of CYP2C8 in retinoic add 4-hydroxylation in human hepatic microsomes. Bio-chem. Pharmacol. 1999, 58, 1201—1208. 

One quality shared by most of the vitamins is their inability to be used in the form in which they are absorbed. Most of the vitamins absorbed from the diet must be converted or modified to the active form. For example, vitamin A, in the form of re tiny I ester, must bo converted to retinoic add to perform some of its functions. Thiamin must be converted to thiamin pyrophosphate to be cocnzymatically active Vitamin K must be reduced to dihydrovitamm K, folate must be poiygiu-tamated, and niacin must be converted to NAD to be active in the cell. 

CRBP is thought to assure that retinol is metaboliby specific enzymes, white preventing metabolism by other en ymes. Por example, by binding retinol, CRBP prevents excessive rates of conversion of retinol to retinoic add (Napoli, 1996). 

Ci s-retinoic acid is a version of vitamin A that, along with all-trflMS-retinoic add, is used as a hormone. 9-OS KA binds to a protein called RXR, while albfra is-RA binds to RAR. 9-Cfs-RA can be formed by cleavage of dietary 9-cr S p Carotenc, or from the enzymatic isomeristation of all-fr HS-RA, at a singJe double bond, 9-Ci s-P-carotene is typically present in the diet, but since it is not a required nutrient and i.s not a vitamin, it is apparent that isomerization of a /M .s-RA may supply ali the 9-l j b-RA that is needed. 

Retinoic add Retinoic acid leceptor RARa. RARg... 

M. Discovery of novel and potent retinoic add receptor alpha agonists syntheses and evaluation of benzofuranyl-pyrrole and benzo-thiophenyl-pyrrole. 7. Med. Chem. 2000, 45, 2929-2937. 

High-pressure FTIR measurements in 2003 [97] indicated that C H 0 bonds help stabilize p-sheets. These interactions were also instrumental in the formation of extended p-strands in a chain containing D-chiral residues [98], A helical hairpin motif was attributed [99] to CH- -O bonds between the side chains of one helix and the backbone of another in 2001. The large number (75) of CH O bonds exceeds the 49 conventional intersubunit H-bonds, indicating that the former contacts determine association and orientation of transmembrane helices in PSI [100]. A detailed survey [101] indicated that these bonds can affect the Trp rotation angle in proteins. These bonds were considered potentially as a driving force for ligand selectivity, as noted in the hydrophobic pocket of retinoic add receptor RARy [102]. 

Balaban, A.T, Catana, C., Dawson, M. and Niculescu-Duvaz, 1. (1990) Applications of weighted topological index / for QSAR of carcinogenesis inhibitors (retinoic add derivatives). Rev. Roum. Chim., 35, 997-1003. 

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