アンチトロンビンIIIのトロンビン阻害作用に及ぼす各種脂肪酸の影響

概要

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In assaying fibrinogen agarose electrophoresis, we found that oleic acid controlled antithrombin III (ATIII) activity depending on the acid concentration. In our assay with synthetic substrates, the inhibition of ATIII progressive activity (PA) by unsaturated fatty acids was at least 4-fold stronger than that by saturated ones. Specifically, the inhibitory activity of oleic acid was 6.7-fold of palmitic acid, and 13.1-fold of stearic acid. 50% inhibition of both PA and heparin cofactor activity (HCA) in 0.86 μM ATIII significantly decreased in the presence of 13 μM oleic acid. There was no difference in PA and HCA resulting from the order of mixing ATIII, oleic acid and heparin, indicating that heparin did not affect the formation of ATIII-oleic acid complex. However the presence of albumin neutralized the ATIII inhibition activity of oleic acid significantly. The addition of albumin to the mixture of oleic acid and ATIII, however, did not restore the ATIII activity, which indicated that albumin could not dissociate oleic acid from ATIII. These results suggest that unsaturated fatty acids inhibit mainly the regulating function of ATIII on coagulation, and that it may give rise to thrombotic disorders.
社団法人日本薬学会の論文
1988-09-25