2-arylpropionyl-CoA epimerase: Partial peptide sequences and tissue localization

被引：27

作者：

Reichel, C ^{[1
]}

Bang, H ^{[1
]}

Brune, K ^{[1
]}

Geisslinger, G ^{[1
]}

Menzel, S ^{[1
]}

机构：

[1] UNIV ERLANGEN NURNBERG,DEPT EXPTL & CLIN PHARMACOL & TOXICOL,D-91054 ERLANGEN,GERMANY

来源：

BIOCHEMICAL PHARMACOLOGY | 1995年 / 50卷 / 11期

关键词：

2-arylpropionyl-CoA epimerase; ibuprofen; amino acid sequence; acyl-CoA-thioester; chiral inversion; anti-epimerase antibodies;

D O I：

10.1016/0006-2952(95)02054-3

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The R-enantiomers of 2-arylpropionic acids (2-APAs) such as ibuprofen (IBU) exhibit the phenomenon of species- and substrate-dependent metabolic chiral inversion. Only R-enantiomers are activated to acyl-CoA-thioesters by an acyl-CoA-synthetase via an adenylate intermediate. The acyl-CoA-thioesters are substrates for an epimerase, which is responsible for chiral inversion. A 42 kDa epimerase from the cytosolic fraction of rat livers was isolated and purified to homogeneity. Polyclonal antibodies were raised against the epimerase in rabbits. The anti-epimerase antibodies were used for affinity column chromatography to separate homogeneous protein for amino acid sequence analysis. Sequence data analysis of 3 internal peptide sequences showed 50% and more homology with regions of enzymes involved in fatty acid metabolism. The polyclonal anti-epimerase antibodies were used to analyze the tissue distribution of the protein in guinea pigs and rats by Western blot analysis. Furthermore, the correlation of inversion enzyme activity ill various tissues under comparable incubation conditions and cross-reactivity in Western blot analysis was investigated.

引用

页码：1803 / 1806

页数：4

共 16 条

[1]

Caldwell, Hutt, Fournel-Gigleux, The metabolic chiral inversion and dispositional enantioselectivity of the 2-arylpropionic acids and their biological consequences, Biochem Pharmacol, 37, pp. 105-114, (1988)

[2]

Knights, Drew, Meffin, Enantiospecific formation of fenoprofen coenzyme A thioester in vitro, Biochem Pharmacol, 37, pp. 3539-3542, (1988)

[3]

Knadler, Hall, Stereoselective arylpropionyl-CoA thioester formation in vitro, Chirality, 2, pp. 67-73, (1990)

[4]

Tracy, Wirthwein, Hall, Metabolic inversion of (R)-ibuprofen. Formation of ibuprofenyl-coenzyme A, Drug Metab Dispos, 21, pp. 114-120, (1993)

[5]

Menzel, Waibel, Brune, Geisslinger, Is the formation of R-ibuprofenyl-adenylate the first stereoselective step of chiral inversion?, Biochem Pharmacol, 48, pp. 1056-1058, (1994)

[6]

Shieh, Chen, Purification and characterization of novel “2-arylpropionyl-CoA epimerases” from rat liver cytosol and mitochondria, J Biol Chem, 268, pp. 3487-3493, (1993)

[7]

Tracy, Hall, Metabolic inversion of R-ibuprofen. Epimerization and hydrolysis of ibuprofenyl-coenzyme A, Drug Metab Dispos, 20, pp. 322-327, (1992)

[8]

Wechter, Drug chirality: On the mechanism of R-aryl propionic acid class NSAIDs. Epimerization in humans and the clinical implications for the use of racemates, J Clin Pharmacol, 34, pp. 1036-1042, (1994)

[9]

Hall, Quan, The role of coenzyme A in the biotransformation of 2-arylpropionic acids, Chem Biol Interact, 90, pp. 235-251, (1994)

[10]

Porubek, Sanins, Stephens, Grillo, Kaiser, Halstead, Adams, Baillie, Metabolic chiral inversion of flurbiprofen-CoA In vitro, Biochemical Pharmacology, 42, pp. R1-R4, (1991)

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