pH对底物和丙二酰辅酶A与线粒体肉碱棕榈酰转移酶I相互作用的影响
Effects of pH on the interaction of substrates and malonyl-CoA with mitochondrial carnitine palmitoyltransferase I.
作者信息
Mills S E, Foster D W, McGarry J D
出版信息
Biochem J. 1984 Apr 15;219(2):601-8. doi: 10.1042/bj2190601.
Abstract
The kinetics of carnitine palmitoyltransferase I (CPT I; EC 2.3.1.21) were examined in mitochondria from rat liver, heart and skeletal muscle as a function of pH over the range 6.8-7.6. In all three tissues raising the pH resulted in a fall in the Km for carnitine, no change in the Km for palmitoyl-CoA or Octanoyl-CoA, and a marked decrease in the inhibitory potency of malonyl-CoA. Studies with skeletal-muscle mitochondria established that increasing pH was accompanied by an increase in the Kd of the malonyl-CoA binding site for this ligand, coupled with a decrease in the Kd for fatty acyl-CoA species to compete for malonyl-CoA binding. Three principal conclusions are drawn. (1) The pH-induced shift in malonyl-CoA sensitivity of CPT I is not a phenomenon restricted to liver mitochondria. (2) At any given pH within the range tested, the ability of malonyl-CoA (and closely related compounds) to inhibit enzyme activity is governed by the efficiency of their binding to the malonyl-CoA site. (3) The competitive interaction between fatty acyl-CoA substrates and malonyl-CoA as regards CPT I activity is exerted at the malonyl-CoA binding site. Finally, the possibility is strengthened that the malonyl-CoA binding site is distinct from the active site of CPT I.
摘要
在pH值范围为6.8至7.6的条件下，研究了大鼠肝脏、心脏和骨骼肌线粒体中肉碱棕榈酰转移酶I（CPT I；EC 2.3.1.21）的动力学。在所有这三种组织中，提高pH值会导致肉碱的Km值下降，棕榈酰辅酶A或辛酰辅酶A的Km值不变，并且丙二酰辅酶A的抑制效力显著降低。对骨骼肌线粒体的研究表明，pH值升高伴随着丙二酰辅酶A结合位点对该配体的解离常数（Kd）增加，同时脂肪酸酰基辅酶A物种竞争丙二酰辅酶A结合的Kd值降低。得出了三个主要结论。（1）pH值诱导的CPT I对丙二酰辅酶A敏感性的变化并非仅限于肝脏线粒体的现象。（2）在所测试的pH值范围内的任何给定pH值下，丙二酰辅酶A（及密切相关化合物）抑制酶活性的能力取决于它们与丙二酰辅酶A位点结合的效率。（3）就CPT I活性而言，脂肪酸酰基辅酶A底物与丙二酰辅酶A之间的竞争性相互作用发生在丙二酰辅酶A结合位点。最后，丙二酰辅酶A结合位点与CPT I活性位点不同的可能性得到了加强。
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