Abstract |
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.
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Authors | Kaori Ueda, Masanori Yoshihara, Michiyasu Nakao, Tamotsu Tanaka, Shigeki Sano, Kenji Fukuzawa, Akira Tokumura |
Journal | Journal of agricultural and food chemistry
(J Agric Food Chem)
Vol. 58
Issue 10
Pg. 6053-63
(May 26 2010)
ISSN: 1520-5118 [Electronic] United States |
PMID | 20415488
(Publication Type: Journal Article)
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Chemical References |
- Enzyme Inhibitors
- Flavonols
- Multienzyme Complexes
- Recombinant Proteins
- Phosphoric Diester Hydrolases
- Phosphodiesterase I
- alkylglycerophosphoethanolamine phosphodiesterase
- Pyrophosphatases
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Topics |
- Binding Sites
- Binding, Competitive
- Enzyme Inhibitors
(pharmacology)
- Flavonols
(pharmacology)
- Humans
- Multienzyme Complexes
(blood)
- Phosphodiesterase I
(blood)
- Phosphoric Diester Hydrolases
(blood)
- Pyrophosphatases
(blood)
- Recombinant Proteins
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