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Biosynthesis of retinoyl-beta-glucuronide, a biologically active metabolite of all-trans-retinoic acid. 1986

D A Miller, and H F DeLuca

All-trans-retinoic acid is metabolized in vitro to a biologically active metabolite, retinoyl-beta-glucuronide. We have studied the synthesis of this metabolite in vitro. The identity of the product was established by cochromatography on reverse-phase high-performance liquid chromatography, beta-D-glucuronidase hydrolysis, and fast atom bombardment and collisionally activated decomposition/fast atom bombardment mass spectrometry. The formation of retinoyl-beta-glucuronide is catalyzed by a UDP-glucuronosyltransferase with apparent Km's of 54.7 microM for all-trans-retinoic acid and 2.4 mM for UDP-glucuronic acid. The reaction requires enzyme, UDP-glucuronate, and no other factor. It is strongly inhibited by millimolar concentrations of coenzyme A. The specific activity of UDP-glucuronosyltransferase is greatest in the liver and least in the kidney of those tissues examined. The specific activity of the enzyme is increased by vitamin A deficiency. The increased specific activity observed in the vitamin A-deficient rat liver is uncharacteristic of retinoic acid inactivation enzymes; therefore, retinoyl-beta-glucuronide may be of functional importance.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D003067 Coenzymes Small molecules that are required for the catalytic function of ENZYMES. Many VITAMINS are coenzymes. Coenzyme,Enzyme Cofactor,Cofactors, Enzyme,Enzyme Cofactors,Cofactor, Enzyme
D005260 Female Females
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013696 Temperature The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms. Temperatures
D014212 Tretinoin An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE). Retinoic Acid,Vitamin A Acid,Retin-A,Tretinoin Potassium Salt,Tretinoin Sodium Salt,Tretinoin Zinc Salt,Vesanoid,all-trans-Retinoic Acid,beta-all-trans-Retinoic Acid,trans-Retinoic Acid,Acid, Retinoic,Acid, Vitamin A,Acid, all-trans-Retinoic,Acid, beta-all-trans-Retinoic,Acid, trans-Retinoic,Potassium Salt, Tretinoin,Retin A,Salt, Tretinoin Potassium,Salt, Tretinoin Sodium,Salt, Tretinoin Zinc,Sodium Salt, Tretinoin,Zinc Salt, Tretinoin,all trans Retinoic Acid,beta all trans Retinoic Acid,trans Retinoic Acid

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