Alcohol Dehydrogenase as a Critical Mediator of Retinoic Acid Synthesis from Vitamin A in the Mouse Embryo

The Burnham Institute, La Jolla, CA 92037

Vitamin A (retinol) must be metabolized to an active retinoid ligand in order to fulfill all of its roles in vertebrate development. During retinoid signaling, retinol is first converted to retinal followed by conversion of retinal to the active ligand retinoic acid, which modulates nuclear retinoic acid receptors (RAR). The alcohol dehydrogenase (ADH) enzyme family may function in the metabolism of retinol, the alcohol form of vitamin A, as well as ethanol metabolism. Some members of the ADH family prefer retinol as a substrate over ethanol, and their ability to oxidize retinol is competitively inhibited by intoxicating levels of ethanol. Likewise, there exists an aldehyde dehydrogenase (ALDH) family containing several members preferring retinal as a substrate over acetaldehyde. The spatiotemporal expression patterns of ADH-IV and two forms of ALDH match the spatiotemporal detection of retinoic acid during mouse embryogenesis, i.e., no detection at 6.5 d of embryogenesis (E6.5), followed by detection at E7.5 in the primitive streak, and then detection in numerous tissues later in development. This suggests that certain forms of ADH and ALDH may cooperate to upregulate retinoic acid synthesis during development. Treatment of mouse embryos at E7.5 with an intoxicating amount of ethanol leads to a reduction in retinoic acid levels. At E7.5, two other mouse enzymes known to metabolize ethanol (ADH-I and P450 2E1) are not expressed, indicating that ADH-IV may be the only enzyme available at this stage to metabolize both ethanol and retinol. These findings suggest that ADH-IV participates in the initiation of retinoid signaling by functioning as a retinol dehydrogenase and that this can be inhibited by ethanol intoxication.

The Journal of Nutrition Vol. 128 No. 2 February 1998, pp. 459S-462S
Copyright ©1998 by the American Society for Nutritional Sciences

This article has been cited by other articles:

				L. D. Nadauld, D. N. Shelton, S. Chidester, H. J. Yost, and D. A. Jones The Zebrafish Retinol Dehydrogenase, rdh1l, Is Essential for Intestinal Development and Is Regulated by the Tumor Suppressor Adenomatous Polyposis Coli J. Biol. Chem., August 26, 2005; 280(34): 30490 - 30495. [Abstract] [Full Text] [PDF]

				J. K. Wickenheisser, V. L. Nelson-DeGrave, K. L. Hendricks, R. S. Legro, J. F. Strauss III, and J. M. McAllister Retinoids and Retinol Differentially Regulate Steroid Biosynthesis in Ovarian Theca Cells Isolated from Normal Cycling Women and Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4858 - 4865. [Abstract] [Full Text] [PDF]

				M. Taimi, C. Helvig, J. Wisniewski, H. Ramshaw, J. White, M.'a. Amad, B. Korczak, and M. Petkovich A Novel Human Cytochrome P450, CYP26C1, Involved in Metabolism of 9-cis and All-trans Isomers of Retinoic Acid J. Biol. Chem., January 2, 2004; 279(1): 77 - 85. [Abstract] [Full Text] [PDF]

				P. McCaffery, J. Evans, O. Koul, A. Volpert, K. Reid, and M. D. Ullman Retinoid quantification by HPLC/MSn J. Lipid Res., July 1, 2002; 43(7): 1143 - 1149. [Abstract] [Full Text] [PDF]

				A Parlesak, I Menzl, A Feuchter, J C Bode, and C Bode Inhibition of retinol oxidation by ethanol in the rat liver and colon Gut, December 1, 2000; 47(6): 825 - 831. [Abstract] [Full Text] [PDF]