METABOLISM OF OXIDIZED LINOLEIC-ACID - CHARACTERIZATION OF 13-HYDROXYOCTADECADIENOIC ACID DEHYDROGENASE-ACTIVITY FROM RAT COLONIC TISSUE

被引:51
作者
EARLES, SM [1 ]
BRONSTEIN, JC [1 ]
WINNER, DL [1 ]
BULL, AW [1 ]
机构
[1] OAKLAND UNIV,DEPT CHEM,ROCHESTER,MI 48309
关键词
13-HYDROXYOCTADECADIENOATE; OXIDIZED LINOLEATE; COLONIC MUCOSAL METABOLISM; 13-HYDROXYOCTADECADIENOATE DEHYDROGENASE;
D O I
10.1016/0005-2760(91)90023-B
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
An oxidized derivative of linoleic acid, 13-hydroxyoctadecadienoic acid (13-HODE), is dehydrogenated by an NAD+ dependent dehydrogenase present in rat colon mucosa. The product of the reaction is the 2,4-dienone, 13-oxooctadecadienoic acid. Enzyme activity was determined by HPLC analysis of incubation mixtures as well as by measuring the increase in absorbance at 285 nm, which represents formation of the 2,4-dienone chromophore. Characteristics of the reaction with respect to protein concentration, time of incubation and substrate dependence were investigated. Several inhibitors of known dehydrogenases had no effect on the 13-HODE dehydrogenase. These include, ethanol, indomethacin, 6-methyl-17-hydroxyprogesterone acetate, 4-(diethylamino)-benzaldehyde, and aspirin. The enzyme was mildly inhibited by pyrazole, 4-methylpyrazole and ibuprofen. Disulfiram was found to be a potent inhibitor of enzyme activity with an IC50 of 200-mu-M. Inhibitor specificity, and other characteristics of the reaction suggest the enzyme is neither alcohol dehydrogenase, diol dehydrogenase, nor a prostaglandin dehydrogenase. It is possible this enzyme plays an important role in the response of the colonic mucosa to the mitogenic effect of oxidized fatty acids.
引用
收藏
页码:174 / 180
页数:7
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