Evaluation of Inhibitory Actions of Flavonols and Related Substances on Lysophospholipase D Activity of Serum Autotaxin by a Convenient Assay Using a Chromogenic Substrate

被引：5

作者：

Ueda, Kaori ^{[1
]}

Yoshihara, Masanori ^{[1
]}

Nakao, Michiyasu ^{[1
]}

Tanaka, Tamotsu ^{[1
]}

Sano, Shigeki ^{[1
]}

Fukuzawa, Kenji ^{[1
]}

Tokumura, Akira ^{[1
]}

机构：

[1] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Tokushima 7708505, Japan

来源：

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY | 2010年 / 58卷 / 10期

关键词：

Autotaxin; lysophosphatidic acid; lysophospholipase D; flavonol; phenolic acid; free fatty acid; LYSOPHOSPHATIDIC ACID; EXPRESSION; IDENTIFICATION; MOTILITY; PHOSPHATASE; PLASMA; CELLS; MECHANISM; GROWTH; FLUIDS;

D O I：

10.1021/jf904155a

中图分类号：

S [农业科学];

学科分类号：

09 ;

摘要：

Overproduction of lysophosphatidic acid (LPA) by lysophospholipase D/autotaxin (lysoPLD/ATX) is postulated to be involved in the promotion of cancer and atherosclerosis. A lysoPLD inhibitor may be utilized to ameliorate the LPA-related pathological conditions. In this study, a new assay was devised to quantify p-nitrophenol from hydrolysis of chromogenic substrate by serum lysoPLD without tedious lipid extraction procedures. Flavonols, phenolic acids, free fatty acids, and N-acyltyrosines inhibited lysoPLD activity in a micromolar range. They were classified into competitive, noncompetitive, or mixed type inhibitors. The results show that the low hydrophobicity of an inhibitor is a critical factor in its preference for the binding to a noncatalytic binding site over a catalytic binding site. Considering its reported bioavailability and the low dependency of its inhibitory activity on serum dilution, flavonol is likely to be a more effective lysoPLD inhibitor in human blood circulation in vivo than the other inhibitors including LPA.

引用

页码：6053 / 6063

页数：11