Advisory Committee Chair
Natalia Y Kedishvili
Advisory Committee Members
Louise T Chow
Thomas M Ryan
Robert A Kesterson
Chenbei Chang
Document Type
Dissertation
Date of Award
2015
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Bioactive vitamin A takes form as several molecules, among them all-trans-retinoic acid (RA) is the major form and influences a wide range of biological processes. RA must be synthesized through a two-step mechanism, where all-trans-retinol is first oxidized to all-trans-retinaldehyde by retinol dehydrogenases (RDHs) and retinaldehyde is further oxidized to RA by retinaldehyde dehydrogenases (RALDHs). The first step, retinol to retinaldehyde conversion is the rate limiting step and therefore a likely target of mechanisms that modulate RA synthesis. Despite this, many of the enzymes that are involved in retinol and retinaldehyde interconversion have yet to be identified and thus many questions remain regarding the mechanisms of RA synthesis regulation. The described work was performed to shed light on these unaddressed issues. Our findings suggest that multiple RDH enzymes exist that possess unique activities and modes of regulation. Further, we conclude that a retinaldehyde reductase (dehydrogenase reductase 3, DHRS3) is essential for the maintenance of retinoid homeostasis in vivo and that it likely functions as part of a feedback regulatory mechanism whereby RA synthesis is influenced by RA concentrations. In summary, this work greatly enhances our understanding of the mechanisms involved in the maintenance of retinoid homeostasis and further illuminates the importance of retinol-retinaldehyde interconversion in this process
Recommended Citation
Adams, Mark, "The Regulation of Vitamin A Metabolism" (2015). All ETDs from UAB. 957.
https://digitalcommons.library.uab.edu/etd-collection/957