Lane M D, Watkins P A, Meredith M J
CRC Crit Rev Biochem. 1979 Dec;7(2):121-41. doi: 10.3109/10409237909105429.
Chick liver cell monolayers synthesize fatty acids at in vivo rates and are responsive to insulin and glucagon. High rates of fatty acid synthesis are maintained with insulin present and lost slowly without insulin. Glucagon or 3',5'-cyclic AMP cause immediate cessation of fatty acid synthesis. The site of inhibition appears to be cytoplasmic acetyl-CoA carboxylase which catalyzes the first committed step of fatty acid synthesis. Liver carboxylase exists either as catalytically inactive protomers or active filamentous polymers. Citrate, an allosteric activator of the enzyme, is required for both catalysis and polymerization. Glucagon and cAMP cause an immediate decrease in the cytoplasmic citrate concentration of chick liver cells apparently by inhibiting the conversion of glucose to citrate at the phosphofructokinase reaction. Since fatty acid synthesis and citrate level are closely correlated, citrate appears to be a feed-forward activator of the carboxylase in vivo. Compelling evidence indicates that carboxylase filaments are present in the intact cell when citrate levels are high and depolymerize when citrate levels fall. Hence, carboxylase activity and fatty acid synthetic rate appear to be determined by cytoplasmic citrate level.
鸡肝细胞单层以体内速率合成脂肪酸，并且对胰岛素和胰高血糖素敏感。在有胰岛素存在的情况下，脂肪酸合成速率较高，而在没有胰岛素的情况下，脂肪酸合成速率会缓慢下降。胰高血糖素或3',5'-环磷酸腺苷会导致脂肪酸合成立即停止。抑制位点似乎是细胞质中的乙酰辅酶A羧化酶，该酶催化脂肪酸合成的第一个关键步骤。肝脏羧化酶要么以无催化活性的单体形式存在，要么以有活性的丝状聚合物形式存在。柠檬酸是该酶的变构激活剂，催化和聚合反应都需要它。胰高血糖素和环磷酸腺苷显然通过抑制磷酸果糖激酶反应中葡萄糖向柠檬酸的转化，使鸡肝细胞细胞质中的柠檬酸浓度立即降低。由于脂肪酸合成与柠檬酸水平密切相关，柠檬酸似乎是体内羧化酶的前馈激活剂。有力的证据表明，当柠檬酸水平较高时，羧化酶细丝存在于完整细胞中，而当柠檬酸水平下降时，羧化酶细丝会解聚。因此，羧化酶活性和脂肪酸合成速率似乎由细胞质柠檬酸水平决定。
