Advisory Committee Chair
Natalia Y Kedishvili
Advisory Committee Members
Herbert C Cheung
Fang-Tsyr Lin
Kirill M Popov
Philip A Wood
Document Type
Dissertation
Date of Award
2008
Degree Name by School
Doctor of Philosophy (PhD) School of Medicine
Abstract
Retinol dehydrogenase 12 (RDH12) is a member of the microsomal short-chain dehydrogenase/reductase superfamily of proteins that is highly expressed in photorecep-tor cells. Mutations in RDH12 are associated with severe early-onset autosomal recessive retinal dystrophy, leading to legal blindness. Disease-associated RDH12 variants exhibit lower protein levels when expressed in eukaryotic cells. However, the physiological role of RDH12 remains unclear. As established previously, RDH12 recognizes both retinoids and lipid peroxidation products (medium-chain aldehydes) as substrates and exhibits the highest catalytic efficiency for all-trans-retinaldehyde. As the main goal of this dissertation, we characterized the catalytic properties of RDH12 and its naturally occurring mutants in vitro and in intact cells. Further, we deter-mined the contribution of RDH12 to retinoid homeostasis and detoxification of lipid per-oxidation. Finally, we determined the biochemical basis for the reduced cellular levels of disease-associated mutants of RDH12. Our findings offer a better understanding of the physiological function of RDH12 in photoreceptor cells and the molecular basis of the disease associated with RDH12 mutations.
Recommended Citation
Lee, Seung-Ah, "Function of Human Retinol Dehydrogenase 12 (RDH12) in Retinoid Metabolism" (2008). All ETDs from UAB. 275.
https://digitalcommons.library.uab.edu/etd-collection/275