Apolipoprotein A-I Regulates Lipid Hydrolysis by Hepatic Lipase*
Apolipoprotein A-I Regulates Lipid Hydrolysis by Hepatic Lipase*
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DOI：
10.1074/jbc.m005436200
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发表时间：
2000-10
期刊：
影响因子：
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通讯作者：
T. Ramsamy;T. Neville;B. Chauhan;Dhiraj Aggarwal;D. Sparks
中科院分区：
文献类型：
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作者：
T. Ramsamy;T. Neville;B. Chauhan;Dhiraj Aggarwal;D. Sparks
肝脂酶（HL）与纯硫酸乙酰肝素蛋白聚糖（HSPG）的结合对高密度脂蛋白（HDL）颗粒的水解影响不大，但显着抑制（>80%）低密度脂蛋白（LDL）和极低密度脂蛋白（VLDL）的水解。脂解抑制作用与脂蛋白从HSPG中去除HL的不同能力有关。LDL和VLDL不能置换HL，而HDL容易从HSPG置换HL。这些数据表明，HSPG结合的HL是无活性的。纯化的载脂蛋白（apo）A-I比HDL更有效地从HSPG中释放HL，HL置换与apoA-I与HSPG的直接结合有关。然而，由apoA-I置换HL并不增强VLDL颗粒的水解。这似乎是由于apoA-I对HL的直接抑制。apoA-I和HDL都能够抑制VLDL脂质水解高达60%。VLDL水解的抑制与apoA-I与VLDL颗粒表面的结合以及伴随的对HL亲和力的降低有关。这些数据表明，载脂蛋白A-I可以通过从细胞表面蛋白聚糖中释放/激活酶以及通过直接调节脂蛋白结合和水解来调节HL的脂质水解。
Association of hepatic lipase (HL) with pure heparan sulfate proteoglycans (HSPG) has little effect on hydrolysis of high density lipoprotein (HDL) particles, but significantly inhibits (>80%) the hydrolysis of low (LDL) and very low density lipoproteins (VLDL). Lipolytic inhibition is associated with a differential ability of the lipoproteins to remove HL from the HSPG. LDL and VLDL are unable to displace HL, whereas HDL readily displaces HL from the HSPG. These data show that HSPG-bound HL is inactive. Purified apolipoprotein (apo) A-I is more efficient than HDL at liberating HL from HSPG, and HL displacement is associated with the direct binding of apoA-I to HSPG. However, displacement of HL by apoA-I does not enhance hydrolysis of VLDL particles. This appears due to the direct inhibition of HL by apoA-I. Both apoA-I and HDL are able to inhibit VLDL lipid hydrolysis by up to 60%. Inhibition of VLDL hydrolysis is associated with the binding of apoA-I to the surface of the VLDL particle and a concomitant decreased affinity for HL. These data show that apoA-I can regulate lipid hydrolysis by HL by liberating/activating the enzyme from cell surface proteoglycans and by directly modulating lipoprotein binding and hydrolysis.