Sheehan P M, Yeh Y Y
Lipids. 1984 Feb;19(2):103-8. doi: 10.1007/BF02534499.
The rate of fatty acid synthesis from acetoacetate (AcAc) is 2-3 times greater than from glucose in developing rat lung. To determine the reason for this difference, we investigated the pathways of lipogenesis from [3-14C] AcAc, [3-14C] beta-hydroxybutyrate (beta OHB), [U-14C] glucose or [2-14C] pyruvate in minced lung tissue of 3- to 4-day-old rats. The addition of (-)hydroxycitrate, an inhibitor of ATP-citrate lyase, inhibited fatty acid synthesis from glucose, pyruvate, and beta OHB by 88%, 70% and 60%, respectively, but had no effect on that from AcAc. Benzene 1,2,3-tricarboxylate, an inhibitor of tricarboxylate translocase, inhibited fatty acid synthesis from all substrates by at least 50%. Incubation with aminooxyacetate, an inhibitor of aspartate aminotransferase, had no effect on lipid synthesis from glucose, pyruvate or AcAc, but increased lipid synthesis from beta OHB. Results indicate that for lipid synthesis in the neonatal lung, acetyl CoA from AcAc is derived predominantly from a cytoplasmic pathway involving AcAcCoA synthetase and AcAcCoA thiolase, whereas citrate is the major route of acetyl group transfer from glucose. Lipogenesis from beta OHB involves both the cytoplasmic and citrate pathways.
在发育中的大鼠肺中，由乙酰乙酸（AcAc）合成脂肪酸的速率比由葡萄糖合成脂肪酸的速率高2至3倍。为了确定这种差异的原因，我们研究了3至4日龄大鼠肺组织匀浆中由[3-14C]AcAc、[3-14C]β-羟基丁酸（βOHB）、[U-14C]葡萄糖或[2-14C]丙酮酸进行脂肪生成的途径。添加ATP-柠檬酸裂解酶抑制剂（-）羟基柠檬酸分别抑制了由葡萄糖、丙酮酸和βOHB合成脂肪酸的过程，抑制率分别为88%、70%和60%，但对由AcAc合成脂肪酸的过程没有影响。三羧酸转运酶抑制剂苯-1,2,3-三羧酸盐抑制了所有底物合成脂肪酸的过程，抑制率至少为50%。用天冬氨酸转氨酶抑制剂氨基氧乙酸孵育，对由葡萄糖、丙酮酸或AcAc进行的脂质合成没有影响，但增加了由βOHB进行的脂质合成。结果表明，对于新生大鼠肺中的脂质合成，来自AcAc的乙酰辅酶A主要来自涉及AcAc辅酶A合成酶和AcAc辅酶A硫解酶的细胞质途径，而柠檬酸是葡萄糖乙酰基转移的主要途径。由βOHB进行的脂肪生成涉及细胞质途径和柠檬酸途径。
