Schindler P W, Ninio E
Pharma Forschung, Hoechst AG, Frankfurt, Germany.
Lipids. 1991 Dec;26(12):1004-10. doi: 10.1007/BF02536492.
Enzyme kinetic studies of lysoPAF acetyltransferase from microsomal preparations of human and rat neutrophils were carried out using lysoPAF or dansyllysoPAF as substrate. With the human enzyme, incomplete conversion of the substrate into the product was observed at 37 degrees C with both substrates. The acetyltransferase was inactivated at 37 degrees C in the absence of substrate with a half-life of 7.5 min. However, the initial rate of product formation under the assay conditions was linear up to 10 min. Both enzymes were optimally active at 40 microM concentration with either substrate, but enzyme activity was inhibited at higher substrate levels. At a constant substrate concentration (40 microM), the Km (microM) and Vmax (nmol product/min/mg protein) values for the human acetyltransferase, with respect to acetyl-CoA were 132 and 23.1, respectively, with lysoPAF as substrate, and 105 and 26.7, respectively, when dansyllysoPAF was used. The Km and Vmax values for the rat enzyme were 105 and 6.5, respectively, with lysoPAF as substrate, and 120 and 5.4, respectively, when dansyllysoPAF was used. Under our standard conditions, lysoPAF required 1 mg of BSA per mL in the assay, whereas full activity of both enzymes was seen with dansyllysoPAF even in the absence of BSA. The results show that dansyllysoPAF can replace lysoPAF in the assay without any significant changes in kinetic parameters.
利用溶血血小板活化因子(lysoPAF)或丹磺酰溶血血小板活化因子(dansyllysoPAF)作为底物,对来自人及大鼠中性粒细胞微粒体制剂的溶血血小板活化因子乙酰转移酶进行了酶动力学研究。对于人源酶,在37℃下使用这两种底物时,均观察到底物未完全转化为产物的情况。在无底物时,乙酰转移酶在37℃下失活,半衰期为7.5分钟。然而,在测定条件下产物形成的初始速率在10分钟内呈线性。两种酶在40微摩尔浓度的任何一种底物下均具有最佳活性,但在较高底物水平下酶活性受到抑制。在恒定底物浓度(40微摩尔)下,以溶血血小板活化因子为底物时,人乙酰转移酶相对于乙酰辅酶A的米氏常数(Km,微摩尔)和最大反应速度(Vmax,纳摩尔产物/分钟/毫克蛋白质)分别为132和23.1,使用丹磺酰溶血血小板活化因子时分别为105和26.7。以溶血血小板活化因子为底物时,大鼠酶的Km和Vmax值分别为105和6.5,使用丹磺酰溶血血小板活化因子时分别为120和5.4。在我们的标准条件下,溶血血小板活化因子在测定中每毫升需要1毫克牛血清白蛋白(BSA),而即使在没有BSA的情况下,使用丹磺酰溶血血小板活化因子时两种酶均表现出完全活性。结果表明,在测定中丹磺酰溶血血小板活化因子可以替代溶血血小板活化因子,而动力学参数无任何显著变化。