一种区分人表皮和银屑病鳞屑中12-羟基二十碳四烯酸立体异构体的酶法。

An enzymatic method for distinguishing the stereoisomers of 12-hydroxyeicosatetraenoic acid in human epidermis and psoriatic scale.

作者信息

Opas E E, Argenbright L W, Humes J L

机构信息

Department of Biochemistry and Molecular Biology, Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065.

出版信息

Br J Dermatol. 1989 Jan;120(1):49-58. doi: 10.1111/j.1365-2133.1989.tb07765.x.

DOI:10.1111/j.1365-2133.1989.tb07765.x

PMID:2517876

Abstract

Homogenates of normal human epidermis synthesized 12-hydroxyeicosatetraenoic acid (12-HETE) when incubated in vitro with arachidonic acid. The stereoconfigurations of the C-12 hydroxyl isomers were determined by incubation with potato 5-lipoxygenase. The synthesized substrate-specific diHETEs; 5S, 12R and 5S, 12S, were readily separated by high performance liquid chromatography. Using this novel methodology, the normal epidermis was found to synthesize predominantly 12-S-HETE while, in contrast, psoriatic scale was found to contain 12-R-HETE. The 5-lipoxygenase inhibitors, Merck L-651, 896, Takeda AA86I, and the active metabolite of Syntex lonapalene were found to inhibit 12-HETE formation in normal epidermal homogenates.

摘要

正常人表皮匀浆在体外与花生四烯酸一起孵育时会合成12-羟基二十碳四烯酸（12-HETE）。通过与马铃薯5-脂氧合酶一起孵育来确定C-12羟基异构体的立体构型。合成的底物特异性二羟基二十碳四烯酸（diHETEs）；5S，12R和5S，12S，很容易通过高效液相色谱法分离。使用这种新方法，发现正常表皮主要合成12-S-HETE，而相比之下，银屑病鳞屑中含有12-R-HETE。发现5-脂氧合酶抑制剂默克L-651、896、武田AA86I以及先灵葆雅洛那帕烯的活性代谢物可抑制正常表皮匀浆中12-HETE的形成。