Ikehata A, Hiwatashi N, Kinouchi Y, Ito K, Yamazaki H, Toyota T
Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Prostaglandins Leukot Essent Fatty Acids. 1993 Jul;49(1):489-94. doi: 10.1016/0952-3278(93)90036-v.
omega-oxidation is regarded as the major pathway for the catabolism of leukotriene B4 (LTB4). To determine how LTB4 omega-hydroxylase is modulated in inflammatory bowel disease, we investigated the kinetic characteristics of this enzyme in 10 patients with Crohn's disease (CD), nine with ulcerative colitis (UC) and eight healthy control subjects. After incubating polymorphonuclear leukocytes with various concentrations of 3H-labeled LTB4, omega-oxidation products were separated by high performance liquid chromatography (HPLC) and the radioactivity was measured by a liquid scintillation counter. The apparent Vmax values were significantly higher in both disease than in healthy control subjects, although the difference between CD and UC was insignificant. There was no difference in the apparent Km values. And the Vmax/Km ratios of patients with CD were significantly higher than that of healthy control subjects. It is suggested that LTB4 metabolism is activated in inflammatory bowel disease (IBD) and that the modulation of this enzyme activity has an important role in the pathogenesis of inflammatory bowel disease.
ω-氧化被认为是白三烯B4(LTB4)分解代谢的主要途径。为了确定LTB4 ω-羟化酶在炎症性肠病中是如何被调节的,我们研究了10例克罗恩病(CD)患者、9例溃疡性结肠炎(UC)患者和8名健康对照者体内该酶的动力学特征。在用不同浓度的3H标记的LTB4孵育多形核白细胞后,通过高效液相色谱法(HPLC)分离ω-氧化产物,并用液体闪烁计数器测量放射性。尽管CD和UC之间的差异不显著,但两种疾病患者的表观Vmax值均显著高于健康对照者。表观Km值没有差异。并且CD患者的Vmax/Km比值显著高于健康对照者。这表明炎症性肠病(IBD)中LTB4代谢被激活,并且该酶活性的调节在炎症性肠病的发病机制中具有重要作用。