| Cellular retinol-binding protein-supported retinoic acid synthesis - Relative roles of microsomes and cytosol |
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| Author(s): Boerman MHEM, Napoli JL |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 271 Issue: 10 Pages: 5610-5616 Published: MAR 8 1996 |
| Times Cited: 67 References: 40 |
| Abstract: This study shows that microsomal retinol dehydrogenases, versus cytosolic retinol dehydrogenases, provide the quantitatively major share of retinal for retinoic acid (RA) biogenesis in rat tissues from the predominant substrate available physiologically, hole-cellular retinol-binding protein, type I (CRBP). With holo-CRBP as substrate in the absence of apo-CRBP microsomal retinol dehydrogenases have the higher specific activity and capacity to generate retinal used for RA synthesis by cytosolic retinal dehydrogenases. In the presence of apo CRBP, a potent inhibitor of cytosolic retinol dehydrogenases (IC50 = similar to 1 mu M), liver microsomes provide 93% of the total retinal synthesized in a combination of microsomes and cytosol. Cytosolic retinol dehydrogenase(s) and the isozymes of alcohol dehydrogenase expressed in rat liver had distinct enzymatic properties; yet ethanol inhibited cytosolic retinol dehydrogenase(s) (IC50 = 20 mu M) while stimulating RA synthesis in a combination of microsomes and cytosol. At least two discrete forms of cytosolic retinol dehydrogenase were observed: NAD- and NADP-dependent forms. Multiple retinal dehydrogenases also were observed and were inhibited partially by apo-CRBP. These results provide new insights into pathways of RA biogenesis and pro vide further evidence that they consist of multiple enzymes that recognize both liganded and nonliganded states of CRBP. |
| Document Type: Article |
| Language: English |
Addresses:
1. SUNY BUFFALO, SCH MED & BIOMED SCI, DEPT BIOCHEM, BUFFALO, NY 14214 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: TZ286 |
| ISSN: 0021-9258 |