Further Observations on the Activation and Inhibition of Lipoprotein Lipase by Apolipoproteins
Further Observations on the Activation and Inhibition of Lipoprotein Lipase by Apolipoproteins
复制标题
载脂蛋白对脂蛋白脂肪酶激活和抑制的进一步观察
作者：
R. Krauss;P. Herbert;R. Levy;D. Fredrickson
ApoC-II 是唯一来自人极低密度脂蛋白的载脂蛋白，可激活大鼠脂肪组织脂蛋白脂肪酶。激活被 apoC-II 抗血清阻断。添加越来越多的激活剂并不会改变脂蛋白脂肪酶（0.32 mM 三油酸甘油酯）的表观 Km，但它确实使表观 Vmax 从 0.8 微摩尔游离脂肪酸/毫克小时−1 逐渐增加到 2.2 微摩尔游离脂肪酸/毫克小时−1。底物浓度高于 1.27 mM 三油酸甘油酯可使 0.25–5.0 μg/ml apoC-II 的活化减少多达 20%。通过将激活剂浓度增加至 50.0 μg/ml，可以逆转这种明显的底物抑制。五种非活化载脂蛋白（apoC-I、C-III-1、C-III-2、A-I 和 A-II）中的每一种都可抑制脂蛋白脂肪酶高达 85-100%。在适当的条件下，ApoC-II 也产生较少的抑制。抑制作用取决于脱辅基蛋白浓度，与底物甘油三酯浓度成反比，并且在非脂蛋白中未观察到抑制作用。非活化载脂蛋白的抑制能力大致相同，与apoC-II浓度无关，并且当非活化载脂蛋白与甘油三酯的比率超过3%(w/w)时发生。这些脱辅基蛋白的部分功能可能是调节脂蛋白脂肪酶对极低密度脂蛋白甘油三酯的水解。
ApoC-II was the only apolipoprotein from human very low density lipoprotein that activated rat adipose tissue lipoprotein lipase. Activation was blocked by antiserum against apoC-II. Addition of increasing amounts of activator did not alter the apparent Km of lipoprotein lipase (0.32 mM triolein), but it did produce a progressive increase in the apparent Vmax from 0.8 to 2.2 μmoles free fatty acid/mg hour−1. Substrate concentrations above 1.27 mM triolein diminished activation by 0.25–5.0 μg/ml of apoC-II as much as 20%. Reversal of this apparent substrate inhibition was achieved by increasing the activator concentration to 50.0 μg/ml. Each of five nonactivating apolipoproteins-apoC-I, C-III-1, C-III-2, A-I, and A-II-inhibited lipoprotein lipase up to 85–100%. ApoC-II also produced less inhibition under appropriate conditions. Inhibition was dependent on apoprotein concentration, inversely related to substrate triglyceride concentration, and unobserved with nonlipoprotein proteins. The inhibitory capacity of the nonactivating apolipoproteins was about the same, was independent of apoC-II concentration, and occurred when the ratio of nonactivator apoprotein to triglyceride exceeded 3% (w/w). It is possible that these apoproteins function partly to modulate the hydrolysis of very low density lipoprotein triglyceride by lipoprotein lipase.