Identification of a New all-trans-Retinol Metabolite Produced through a New Retinol Metabolic Pathway
详细信息 查看全文
- 作者：Xiujuan Jia ; Rafal R. Sicinski ; Deneen M. Wellik ; Praveen Tadikonda ; Heinrich K. Schnoes ; and Hector F. DeLuca
- 刊名：Biochemistry
- 出版年：1998
- 出版时间：April 28, 1998
- 年：1998
- 卷：37
- 期：17
- 页码：5974 - 5980
- 全文大小：155K
- 年卷期：v.37,no.17(April 28, 1998)
- ISSN：1520-4995
文摘
In vitro incubation of all-trans-retinol(atROL) with kidney homogenate from vitaminA-deficient and retinoic acid-supplemented (VAD-RAS) female ratsproduces a new retinol metabolite.Reverse-phase (RP) and normal-phase (NP) high-performance liquidchromatography (HPLC) analysisshowed that this metabolite coelutes with the unknownall-trans-retinol (atROL) metabolitepreviouslyfound in the day 10 conceptus and kidneys of vitamin A-deficient ratsmaintained onall-trans-retinoicacid (VAD-RA) and given 2 
g of [3H]atROL.Normal-phase (NP) HPLC purification of the metabolitecollected from a RP HPLC column further separated the radiolabeledmaterial into two components. Thetwo isolated compounds have identical or very similar spectroscopicproperties. Their nuclear magneticresonance (1H NMR) and mass spectra (MS) indicated thatthey are isomers. Spectroscopic studies ofthe metabolites and their derivatives showed that they are nine-carbonfragments resulting from an oxidativecleavage of the side chain of atROL. The cleavage occurs at C-9,and the product is then oxidized to aketo group. The primary hydroxy group from atROL is preserved inthe metabolite. A sulfide bridge isformed between C-11 and C-14, which interrupts the conjugation.The formation of the new metabolites,possessing a 2,5-dihydrothiophene ring, is catalyzed by anenzyme(s) located in the cytosolic fraction ofkidneys. The process represents a new retinol metabolic pathway;however, its biological significance isunknown.
g of [3H]atROL.Normal-phase (NP) HPLC purification of the metabolitecollected from a RP HPLC column further separated the radiolabeledmaterial into two components. Thetwo isolated compounds have identical or very similar spectroscopicproperties. Their nuclear magneticresonance (1H NMR) and mass spectra (MS) indicated thatthey are isomers. Spectroscopic studies ofthe metabolites and their derivatives showed that they are nine-carbonfragments resulting from an oxidativecleavage of the side chain of atROL. The cleavage occurs at C-9,and the product is then oxidized to aketo group. The primary hydroxy group from atROL is preserved inthe metabolite. A sulfide bridge isformed between C-11 and C-14, which interrupts the conjugation.The formation of the new metabolites,possessing a 2,5-dihydrothiophene ring, is catalyzed by anenzyme(s) located in the cytosolic fraction ofkidneys. The process represents a new retinol metabolic pathway;however, its biological significance isunknown.