Biochemical properties, tissue expression, and gene structure of a short chain dehydrogenase/reductase able to catalyze cis-retinol oxidation

Mary V. Gamble; Enyuan Shang; Roseann Piantedosi Zott; James R. Mertz; Debra J. Wolgemuth; William S. Blaner

Journal of Lipid Research (Dec 1999)

Biochemical properties, tissue expression, and gene structure of a short chain dehydrogenase/reductase able to catalyze cis-retinol oxidation

Mary V. Gamble,
Enyuan Shang,
Roseann Piantedosi Zott,
James R. Mertz,
Debra J. Wolgemuth,
William S. Blaner

Affiliations

Mary V. Gamble: Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, 630 W. 168th Street, New York, NY 10032; the Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 W. 168th Street, New York, NY 10032
Enyuan Shang: Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, 630 W. 168th Street, New York, NY 10032
Roseann Piantedosi Zott: the Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 W. 168th Street, New York, NY 10032
James R. Mertz: Department of Biology, City College of New York, New York, NY 10031
Debra J. Wolgemuth: Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, 630 W. 168th Street, New York, NY 10032; Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, 630 W. 168th Street, New York, NY 10032; Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, 630 W. 168th Street, New York, NY 10032
William S. Blaner: To whom correspondence should be addressed.; Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, 630 W. 168th Street, New York, NY 10032; the Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 W. 168th Street, New York, NY 10032

Journal volume & issue: Vol. 40, no. 12
pp. 2279 – 2292

Abstract

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We have identified a retinol dehydrogenase (cRDH) that catalyzes the oxidation of 9-cis- but not all-trans-retinol and proposed that this enzyme plays an important role in synthesis of the transcriptionally active retinoid, 9-cis-retinoic acid. There is little information regarding either the biochemical properties of cRDH or how its 9-cis-retinol substrate is formed. We now report studies of the properties and expression of human and mouse cRDH and of the characteristics and location of the murine cRDH gene. Additionally, we report mouse hepatic 9-cis-retinol concentrations and demonstrate that 9-cis-retinol is formed in a time- and protein-dependent manner upon incubation of all-trans-retinol with cell homogenate. Human and mouse cRDH display similar substrate specificities for cis-isomers of retinol and retinaldehyde. Moreover, human and mouse cRDH show marked sensitivity to inhibition by 13-cis-retinoic acid, with both being inhibited by approximately 50% by 0.15 μm 13-cis-retinoic acid (for substrate concentrations of 10 μm). Lesser inhibition is seen for 9-cis- or all-trans-retinoic acids. Immunoblot analysis using antiserum directed against human cRDH demonstrates cRDH expression in several tissues from first trimester human fetuses, indicating that cRDH is expressed early in embryogenesis. Adult mouse brain, liver, kidney, and to a lesser extent small intestine and placenta express cRDH. The murine cRDH gene consists of at least 5 exons and spans approximately 6 kb of genomic DNA. Backcross analysis mapped the mouse cRDH gene to the most distal region of chromosome 10. Taken together, these data extend our understanding of the properties of cRDH and provide additional support for our hypothesis that cRDH may play an important role in 9-cis-retinoic acid formation.—Gamble, M. V., E. Shang, R. P. Zott, J. R. Mertz, D. J. Wolgemuth, and W. S. Blaner. Biochemical properties, tissue expression, and gene structure of a short chain dehydrogenase/reductase able to catalyze cis-retinol oxidation.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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