Geelen M J
Laboratory of Veterinary Biochemistry, Utrecht, The Netherlands.
Biochem J. 1994 Aug 15;302 ( Pt 1)(Pt 1):141-6. doi: 10.1042/bj3020141.
Short-term exposure of isolated rat hepatocytes to short- and medium-chain fatty acids led to an activation of acetyl-CoA carboxylase as measured in digitonin-permeabilized hepatocytes. Up to a certain concentration, typical for each of the fatty acids used, fatty acid-dependent activation of acetyl-CoA carboxylase coincided with an increase in the rate of fatty acid synthesis in intact hepatocytes, as determined by the incorporation of 3H from 3H2O water into fatty acids. At higher concentrations loss of stimulation of fatty acid synthesis occurred, but not the enhancement of carboxylase activity. With the fatty acids tested (C8:0-C14:0), the peak in fatty acid synthesis coincided with a peak in the level of malonyl-CoA. The onset of the stimulation of carboxylase activity coincided with the start of the peak in both fatty acid synthesis and malonyl-CoA. The longer the chain length of the fatty acid added, the lower the concentration at which the rate of fatty acid synthesis and the level of malonyl-CoA reached a peak and carboxylase activity started to become elevated. In cell suspensions incubated with increasing concentrations of fatty acids, accumulation of lactate decreased progressively. The latter observation, in combination with the fact that the activity of acetyl-CoA carboxylase is not always related to the rate of fatty acid biosynthesis, suggests that under these conditions not the activity of the carboxylase but the flux through the glycolytic sequence determines, at least in part, the rate of fatty acid synthesis de novo.
将分离的大鼠肝细胞短期暴露于短链和中链脂肪酸，会导致乙酰辅酶A羧化酶激活，这在洋地黄皂苷透化的肝细胞中得到了测定。在达到每种所用脂肪酸特有的一定浓度之前，脂肪酸依赖性乙酰辅酶A羧化酶的激活与完整肝细胞中脂肪酸合成速率的增加相一致，这是通过将3H2O中的3H掺入脂肪酸来确定的。在更高浓度下，脂肪酸合成的刺激作用丧失，但羧化酶活性并未增强。在所测试的脂肪酸（C8:0 - C14:0）中，脂肪酸合成的峰值与丙二酰辅酶A水平的峰值相一致。羧化酶活性刺激的起始与脂肪酸合成和丙二酰辅酶A峰值的开始相一致。添加的脂肪酸链长度越长，脂肪酸合成速率和丙二酰辅酶A水平达到峰值以及羧化酶活性开始升高时的浓度就越低。在用浓度不断增加的脂肪酸孵育的细胞悬液中，乳酸的积累逐渐减少。后一观察结果，再加上乙酰辅酶A羧化酶的活性并不总是与脂肪酸生物合成速率相关这一事实，表明在这些条件下，至少部分地是糖酵解序列的通量而非羧化酶的活性决定了从头脂肪酸合成的速率。
