REGULATION OF CARNITINE PALMITOYLTRANSFERASE ACTIVITY BY MALONYL-COA IN MITOCHONDRIA FROM SHEEP LIVER, A TISSUE WITH A LOW CAPACITY FOR FATTY-ACID SYNTHESIS

REGULATION OF CARNITINE PALMITOYLTRANSFERASE ACTIVITY BY MALONYL-COA IN MITOCHONDRIA FROM SHEEP LIVER, A TISSUE WITH A LOW CAPACITY FOR FATTY-ACID SYNTHESIS
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DOI:
10.1042/bj2320177
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发表时间:
1985-01-01
影响因子:
4.1
通讯作者:
POGSON, CI
POGSON, CI
中科院分区:
生物学3区
文献类型:
--
作者:
BRINDLE, NPJ;ZAMMIT, VA;POGSON, CI

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1.研究了丙二酰辅酶A对羊肝线粒体中肉毒碱棕榈酰转移酶(CPT)I的抑制特性,羊肝是一种脂肪酸合成速率非常低的组织。2.丙二酰辅酶A在抑制绵羊肝酶方面与在抑制大鼠肝线粒体中的酶方面一样有效。豚鼠肝线粒体中的CPT I也被类似地抑制。抑制表现出相同的时间依赖性特征先前建立的大鼠肝酶。3.甲基丙二酰辅酶A是一种有效的抑制剂,CPT我丙二酰辅酶A在绵羊肝线粒体,但不影响CPT我在大鼠或豚鼠肝线粒体的活性。4.在体外抑制绵羊肝线粒体中CPT I所需的丙二酰辅酶A浓度与冷冻夹持的绵羊肝样品中发现的浓度相似(约7 nmol丙二酰辅酶A/g湿重)。5.在绵羊肝细胞中,丙二酰辅酶A的含量仅为仅向孵育培养基中加入葡萄糖时体内观察到的含量的十分之一。包含乙酸盐和/或胰岛素使丙二酰辅酶A含量增加约10倍,达到与体内观察到的值相似的值。6.绵羊肝细胞中的脂肪酸合成率约为大鼠肝脏中观察到的脂肪酸合成率的1%,但在各种孵育条件下与细胞中丙二酰辅酶A的浓度相关。7.这些意见进行了讨论,有关(一)的调节作用,丙二酰辅酶A在组织中,有一个低的脂肪酸合成能力,及(ii)利用羊肝丙酸作为一个pneumeogenic前体。
1. The characteristics of inhibition of carnitine palmitoyltransferase (CPT) I by malonyl-CoA were studied for the enzyme in mitochondria isolated from sheep liver, a tissue with a very low rate of fatty acid synthesis. 2. Malonyl-CoA was as potent in inhibiting the sheep liver enzyme as in inhibiting the enzyme in rat liver mitochondria. CPT I in guinea-pig liver mitochondria was also similarly inhibited. The inhibition showed the same time-dependent characteristics previously established for the rat liver enzyme. 3. Methylmalonyl-CoA was as effective an inhibitor of CPT I as malonyl-CoA in sheep liver mitochondria, but did not affect CPT I activity in mitochondria from rat or guinea-pig liver. 4. The concentrations of malonyl-CoA required to inhibit CPT I in sheep liver mitochondria in vitro were similar to those found in freeze-clamped sheep liver samples (about 7 nmol of malonyl-CoA/g wet wt.). 5. In sheep liver cells the content of malonyl-CoA was only one-tenth of that observed in vivo when glucose only was added to the incubation medium. Inclusion of acetate and/or insulin increased the malonyl-CoA content about 10-fold, to values similar to those observed in vivo. 6. The rate of fatty acid synthesis in sheep liver cells was about 1% of that observed in rat liver, but was correlated with the concentrations of malonyl-CoA in the cells under various incubation conditions. 7. These observations are discussed in relation to (i) the regulatory role of malonyl-CoA in tissues that have a low capacity for fatty acid synthesis, and (ii) the utilization by sheep liver of propionate as a gluconeogenic precursor.