Fatty acids stimulate phosphatidylcholine synthesis and CTP:choline-phosphate cytidylyltransferase in type II pneumocytes isolated from adult rat lung.
Fatty acids stimulate phosphatidylcholine synthesis and CTP:choline-phosphate cytidylyltransferase in type II pneumocytes isolated from adult rat lung.
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脂肪酸刺激从成年大鼠肺中分离的 II 型肺细胞中的磷脂酰胆碱合成和 CTP：磷酸胆碱胞苷酰转移酶。
DOI：
10.1042/bj2540495
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
L. V. van Golde
中科院分区：
文献类型：
--
作者：
R. Burkhardt;P. von Wichert;J. J. Batenburg;L. V. van Golde
研究了环AMP和脂肪酸对大鼠II型肺泡细胞中磷脂酰胆碱(PC)合成的调节。与肝细胞的结果相反，在 II 型肺泡细胞的脉冲追踪研究中，环 AMP 及其有效的氯苯硫基类似物对 [Me-14C] 胆碱掺入 PC 没有抑制作用。在Chase孵育培养基中添加脂肪酸棕榈酸酯、油酸酯或亚油酸酯刺激了II型细胞将[Me-14C]胆碱掺入PC中。棕榈酸酯的作用比其他脂肪酸更明显，并且似乎具有浓度依赖性。 [Me-14C]胆碱掺入PC的增加与磷酸胆碱放射性标记的加速消失相平行，这与CTP：磷酸胆碱胞苷酰转移酶的激活一致。该酶被认为是 II 型细胞从头合成 PC 的限速酶。由于脂肪酸也是 PC 合成的底物，因此它们的作用也可能是由于脂肪酸缺乏的补偿。为了测试这种可能性，通过添加乳酸来刺激 II 型细胞中的脂肪酸合成。即使如此，仍观察到棕榈酸酯对 PC 合成的额外刺激，这支持了外源脂肪酸的调节影响。在 0.2 mM 棕榈酸酯存在下孵育 II 型细胞导致膜结合 CTP：磷酸胆碱胞苷酰转移酶活性增加 45%，而可溶性活性保持不变。可溶部分中的胆碱激酶活性增加了 48%。然而，胆碱激酶的增加不太可能导致通过磷酸胆碱途径的代谢通量增加，因为II型细胞中存在相对较大的磷酸胆碱库。因此，表明微粒体CTP：磷酸胆碱胞苷酰转移酶是该酶的形式，其在表面活性剂PC合成中具有活性，并且可能在此途径中具有调节作用。
The regulation by cyclic AMP and fatty acids of phosphatidylcholine (PC) synthesis in rat alveolar type II cells was studied. In contrast with results with hepatocytes, cyclic AMP and its potent chlorophenylthio analogue had no inhibitory effect on [Me-14C]choline incorporation into PC in pulse-chase studies with alveolar type II cells. The inclusion of the fatty acids palmitate, oleate or linoleate in the chase incubation medium stimulated the incorporation of [Me-14C]choline into PC by type II cells. The effect of palmitate, which was more pronounced than that of the other fatty acids, appeared to be concentration-dependent. Increased [Me-14C]choline incorporation into PC was paralleled by an accelerated disappearance of the radiolabel from choline phosphate, which is consistent with an activation of CTP:choline-phosphate cytidylyltransferase. This enzyme is considered to be rate-limiting in the synthesis of PC de novo by type II cells. As fatty acids are also substrate for PC synthesis, their effect could also be due to compensation for a fatty acid deficiency. To test this possibility, fatty acid synthesis in the type II cells was stimulated by addition of lactate. Even then, an additional stimulation of PC synthesis by palmitate was observed, which supports the regulatory influence of exogenous fatty acids. Incubation of type II cells in the presence of 0.2 mM-palmitate resulted in a 45% increase in the membrane-bound CTP:choline-phosphate cytidylyltransferase activity, whereas the soluble activity remained unchanged. Choline kinase activity in the soluble fraction increased by 48%. However, the increase in choline kinase is unlikely to be responsible for the increased metabolic flux through the choline phosphate pathway, because there is a relatively large pool of choline phosphate in type II cells. Therefore it is suggested that the microsomal CTP:choline-phosphate cytidylyltransferase is the form of this enzyme which is active in surfactant PC synthesis, and possibly has a regulatory role in this pathway.