Karanian J W, Kim H Y, Salem N
Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcoholism and Alcohol Abuse, National Institutes of Health, Rockville, Maryland 20852, USA.
Lipids. 1996 Mar;31 Suppl:S305-8. doi: 10.1007/BF02637097.
The effect of hydroperoxy and hydroxy derivatives of various fatty acids on human platelet aggregation was determined to delineate potencies and structure-activity function. In this regard, the 22-carbon n-3 fatty acids are the most potent inhibitors in comparison to the n-6 lipoxygenase derivatives. Submicromolar levels of the docosapentaenoic (22:5) and especially docosahexaenoic (22:6) n-3 hydroperoxy and hydroxy derivatives specifically antagonize the platelet aggregating effect to arachidonic acid (AA, 20:4n-6) but not that of ADP or collagen. Chain length (22-C > 20-C), double-bond position (n-3 > n-6), and double-bond number (6 > 5 > 4) influence the degree of inhibition of AA-induced aggregation of human platelets. Moreover, significant differences in potency were associated with specific structural aspects of 22:6n-3 lipoxygenase derivatives of 22:6n-3 as follows: functional group (OOH > OH) and positional isomer (14-OOH, 14-OH, 20-OOH > 11-OOH, 17-OOH > 10-OOH > 11-OH, 8-OOH, 7-OOH > 4-OOH).
测定了各种脂肪酸的氢过氧基和羟基衍生物对人血小板聚集的影响，以确定其效力和构效功能。在这方面，与n-6脂氧合酶衍生物相比，22碳的n-3脂肪酸是最有效的抑制剂。亚微摩尔水平的二十二碳五烯酸（22:5），尤其是二十二碳六烯酸（22:6）的n-3氢过氧基和羟基衍生物可特异性拮抗花生四烯酸（AA，20:4n-6）诱导的血小板聚集作用，但对ADP或胶原诱导的血小板聚集作用无影响。链长（22碳>20碳）、双键位置（n-3>n-6）和双键数量（6>5>4）会影响AA诱导的人血小板聚集的抑制程度。此外，22:6n-3脂氧合酶衍生物的效力差异与特定结构方面有关，具体如下：官能团（OOH>OH）和位置异构体（14-OOH、14-OH、20-OOH>11-OOH、17-OOH>10-OOH>11-OH、8-OOH、7-OOH>4-OOH）。
