9-<i>cis</i>-Retinoids:  Biosynthesis of 9-<i>cis-</i>Retinoic Acid

Paik, Ji-Sun; Vogel, Silke; Piantedosi, Roseann; Sykes, A.; Blaner, William S.; Swisshelm, Karen

doi:10.1021/bi992152g

Cited by 30 publications

(38 citation statements)

References 45 publications

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“…Retinol and Retinyl Ester Analysis-Retinoid extractions and detections were carried out as described previously (16,22 Retinoic Acid Analysis from Testes-Intratesticular retinoic acid (RA) concentrations were measured by LC-MS/MS as described previously with a few modifications to the sample preparation (23). All sample processing, preparation, and extraction were conducted on ice under red light to minimize degradation of retinoic acids.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Retinoic Acid Biosynthesis by the Bisdichloroacetyldiamine WIN 18,446 Markedly Suppresses Spermatogenesis and Alters Retinoid Metabolism in Mice

Paik¹,

Haenisch²,

Müller³

et al. 2014

Journal of Biological Chemistry

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Section: Methodsmentioning

confidence: 99%

Inhibition of Retinoic Acid Biosynthesis by the Bisdichloroacetyldiamine WIN 18,446 Markedly Suppresses Spermatogenesis and Alters Retinoid Metabolism in Mice

Paik¹,

Haenisch²,

Müller³

et al. 2014

Journal of Biological Chemistry

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“…For RalR1 activity, microsomal fractions of RalR1/CHO cells were obtained using a method described earlier [20]. Briefly, cells were grown to confluence, washed three times with ice cold PBS, and scraped into a buffer containing 25 mM Tris HCl pH7.5, 0.25 M sucrose, and 1 mM DTT.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

In vitro and in vivo characterization of retinoid synthesis from β-carotene

Fierce

Vieira

Piantedosi

et al. 2008

Archives of Biochemistry and Biophysics

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Retinoids are indispensable for the health of mammals, which cannot synthesize retinoids de novo. Retinoids are derived from dietary provitamin A carotenoids, like β-carotene, through the actions β-carotene 15,15′ monooxygenase (BCMO1). As the substrates for retinoid metabolizing enzymes are water insoluble, they must be transported intracellularly bound to cellular retinol-binding proteins. Our studies suggest that cellular retinol binding protein, type I (RBP1) acts as an intracellular sensor of retinoid status that, when present as apo-RBP1, stimulates BCMO1 activity and the conversion of carotenoids to retinoids. Cellular retinol binding protein, type II (RBP2), which is 56% identical to RBP1 does not influence BCMO1 activity. Studies of mice lacking BCMO1 demonstrate that BCMO1 is responsible for metabolically limiting the amount of intact β-carotene that can be absorbed by mice from their diet. Our studies provide new insights into the regulation of BCMO1 activity and the physiological role of BCMO1 in living organisms. Keywordsβ-carotene; cleavage; β-carotene 15; 15′ monooxygenase; retinoid; metabolism; cellular retinol binding protein Retinoids (vitamin A, its natural metabolites and synthetic analogs) are required for survival of mammals and are needed to support vision, normal cell differentiation and proliferation, embryonic development, normal immune function and reproduction [1]. Aside from in vision, all of the essential actions of retinoids within the body are thought to involve the transcriptional activity of retinoic acid [1]. Retinoic acid is a potent transcriptional regulator whose effects are mediated by two families of nuclear receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs) [2][3][4]. When retinoic acid is not available, RAR/RXR heterodimers bind to retinoic acid response elements in promoter of genes and form complexes with transcriptional corepressors resulting in chromatin condensation and transcriptional silencing. In the presence of retinoic acid, corepressors are released from the RAR/RXR heterodimer which is now free to recruit and bind coactivators resulting in chromatin *Corresponding author: Jisun Paik, Department of Comparative Medicine, Raitt Hall, 324, Seattle, WA 98195. Phone: 206-221-2682; Fax: 206-685-1696; E-mail: jpaik@u.washington.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript decondensation and transcriptional activation. In excess of 500 genes may be responsive to retinoic acid [5].Since ani...

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“…Production-The RDH5 gene product has been implicated in the production of 9-cis-retinal before this aldehyde is further oxidized to 9-cis-retinoic acids (12,14). However, disabling mutations in men and mice produce no embryonic developmental abnormalities (16)(17)(18)(19).…”

Section: Involvement Of Rdh11-14 In Retinoid Transformation and All-tmentioning

confidence: 99%

“…An enzyme encoded by the RDH5 gene (10,11), 11-cis-RDH, was proposed to be responsible for both 11-cis-retinal and 9-cis-retinal production due to its relaxed substrate specificity (12)(13)(14)(15). However, the disruption of this gene in a mouse model led to uninterrupted production of 11-cis-retinal (16,17) and a lack of any embryonic abnormalities.…”

mentioning

confidence: 99%

Dual-substrate Specificity Short Chain Retinol Dehydrogenases from the Vertebrate Retina

Haeseleer¹,

Jang²,

Imanishi³

et al. 2002

Journal of Biological Chemistry

189

227

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Retinoids are chromophores involved in vision, transcriptional regulation, and cellular differentiation. Members of the short chain alcohol dehydrogenase/reductase superfamily catalyze the transformation of retinol to retinal. Here, we describe the identification and properties of three enzymes from a novel subfamily of four retinol dehydrogenases (RDH11-14) that display dualsubstrate specificity, uniquely metabolizing all-trans-and cis-retinols with C 15 pro-R specificity. RDH11-14 could be involved in the first step of all-trans-and 9-cis-retinoic acid production in many tissues. RDH11-14 fill the gap in our understanding of 11-cis-retinal and all-trans-retinal transformations in photoreceptor (RDH12) and retinal pigment epithelial cells (RDH11). The dualsubstrate specificity of RDH11 explains the minor phenotype associated with mutations in 11-cisretinol dehydrogenase (RDH5) causing fundus albipunctatus in humans and engineered mice lacking RDH5. Furthermore, photoreceptor RDH12 could be involved in the production of 11-cis-retinal from 11-cis-retinol during regeneration of the cone visual pigments. These newly identified enzymes add new elements to important retinoid metabolic pathways that have not been explained by previous genetic and biochemical studies.Retinoids are indispensable light-sensitive elements of vision and also serve as essential modulators of cellular differentiation and proliferation in diverse cell types, including those comprising the epithelium and immune system. Retinoids modulate the growth of both normal and malignant cells through their binding to retinoid receptors. All-trans-retinoic acid signals through specific interactions with the nuclear retinoic acid receptors, whereas its isomer, 9-cis-retinoic acid, is a high affinity ligand of retinoic acid receptors and retinoid X receptors. In the retina, light-dependent photoisomerization of 11-cis-retinylidene to the all-transretinylidene moiety of rod and cone photoreceptors is a key reaction that triggers visual * This research was supported by National Institutes of Health Grants EY08061, CA75173, and DK59125, a grant from Research to Prevent Blindness, Inc. (to the Department of Ophthalmology, University of Washington), and by the E. K. Bishop Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. S The on-line version of this article (available at http://www.jbc.org) contains Supplemental Figs. 1 and 2 and Tables 1-3. § These authors contributed equally to this work. § § Recipient of a Research to Prevent Blindness Senior Investigator Award. To whom correspondence should be addressed: Dept. of Ophthalmology, University of Washington, Seattle,; E-mail: palczews@u.washington.edu. Transformations of retinoids occur mostly through enzymatic or photochemical reactions, although they readily isomerize non-enzymatically to thermodynamic equilibriu...

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9-cis-Retinoids: Biosynthesis of 9-cis-Retinoic Acid

Cited by 30 publications

References 45 publications

Inhibition of Retinoic Acid Biosynthesis by the Bisdichloroacetyldiamine WIN 18,446 Markedly Suppresses Spermatogenesis and Alters Retinoid Metabolism in Mice

Inhibition of Retinoic Acid Biosynthesis by the Bisdichloroacetyldiamine WIN 18,446 Markedly Suppresses Spermatogenesis and Alters Retinoid Metabolism in Mice

In vitro and in vivo characterization of retinoid synthesis from β-carotene

Dual-substrate Specificity Short Chain Retinol Dehydrogenases from the Vertebrate Retina

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