Retinoic acid esterification

Retinoic acid regulates its own synthesis from retinol in a variety of tissues by induction of LRAT this increases the rate of esterification of retinol, thereby decreasing the amount available for oxidation to retinoic acid (Kurlandsky et al., 1996). Retinoic acid also induces the cytochrome P450 that catalyzes oxidation to 4-oxo-retinoic acid, and regulates both its own synthesis and catabolism. 

Kurlandsky SB, Duell EA, Kang S, Voorhees JJ, and Fisher GJ (1996) Auto-regulation of retinoic acid biosynthesis through regulation of retinol esterification in human keratinocytes./owrna/ of Biological Chemistry 271,15346-52. 

Wolf G (2001) Retinoic acid homeostasis retinoic acid regulates liver retinol esterification as well as its own catabolic oxidation in liver. Nutrition Reviews 59,391. ... 

Ross, A. C. 2003. Retinoid Production and Catabolism Role of Diet in Regulating Retinol Esterification and Retinoic Acid Oxidation. J Nutr 133, no 1 291s-96s. 

Because of the inherent instability of labeled retinol, the usual practice is to store this compound as a more stable ester (e.g., retinyl acetate) or to keep it in the retinoic acid stage from which it can be prepared by reduction. From esters like the acetate, retinol can be obtained by hydrolysis with base or even by reduction with lithium aluminum hydride at low temperature. For this conversion, a trans-esterification in methanol is preferred, with catalysis by trace amounts of sodium methoxide followed by purification of the retinol by HPLC (Kaegi and Bupp, 1982). 

In the past, retinyl acetate has been prepared from labeled retinoic acid by the following procedure. Esterification of crystallized al -trans-Tciinoic acid with diazomethane and subsequent reduction of the methyl all-fraw -retinoate with lithium aluminum hydride at low temperature yielded M-trans-rctinol, which was acetylated in situ with acetyl chloride and pyridine in ether to give M-trans-retinyl acetate. 

The enzymatic hydrolysis of retinyl esters in liver has been examined in retinol-depleted, retinoic acid-supplemented rats (Harrison et al., 1979) as well as in normal rats (Prystowsky et al., 1981). In both studies, the enzyme retinyl palmitate hydrolase showed an unusual subcellular distribution, being found in the nuclear, mitochondrial, and supernatant fractions and displayed a large variability in activity from rat to rat. For additional information regarding the esterification and hydrolysis of retinol the reader is again referred to Chapters 7 and 10. 

Ross AC (2003) Retinoid production and catabolism Role of diet in regulating retinol esterification and retinoic acid oxidation. Journal of Nutrition 133(suppl) 291S-296S. 

The usual method of esterification and reduction with lithium aluminum hydride at low temperature on purified all-fran -a-retinoic-ll- H acid afforded all-rra 5-a-retinol, as described by Hale et aL (1977). Because the alcohol was found to be quite unstable, acetyl chloride and pyridine were used to convert it to the acetate. The much more stable acetate was then purified by chromotography over alumina. 

---