Wilson S B, Back D W, Morris S M, Swierczynski J, Goodridge A G
J Biol Chem. 1986 Nov 15;261(32):15179-82.
Mechanisms involved in the multihormonal regulation of fatty acid synthase have been investigated by comparing levels of its mRNA with rates of enzyme synthesis in chick embryo hepatocytes in culture. Triiodothyronine or insulin caused about a 2.5-fold increase in the relative rate of synthesis of fatty acid synthase. Together, these hormones were synergistic, stimulating enzyme synthesis by nearly 40-fold (Fischer, P.W.F., and Goodridge, A.G. (1978) Arch. Biochem. Biophys. 190, 332-344). Addition of triiodothyronine stimulated increases in mRNA levels comparable to increases in enzyme synthesis whether insulin was present or not. Thus, triiodothyronine regulates fatty acid synthase primarily by controlling the amount of its mRNA. Addition of insulin, in the presence of triiodothyronine, stimulated enzyme synthesis by 14-fold and mRNA levels by only 2-fold. In the absence of triiodothyronine, insulin had no effect on mRNA levels. Thus, insulin has a major effect on the translation of fatty acid synthase mRNA. After the addition of triiodothyronine, fatty acid synthase mRNA accumulated with sigmoidal kinetics, approaching a new steady state about 48 h after the addition of hormone. Puromycin, an inhibitor of protein synthesis, blocked the effect of triiodothyronine. We suggest that the abundances of both fatty acid synthase and malic enzyme mRNAs are regulated by a common triiodothyronine-induced peptide intermediate which has a relatively long half-life. Glucagon caused an 80% decrease in the synthesis of fatty acid synthase (Fischer, P.W.F., and Goodridge, A.G. (1978) Arch. Biochem. Biophys. 190, 332-344) and a 60% decrease in the level of fatty acid synthase mRNA. Thus, glucagon regulates fatty acid synthase by controlling the concentration of its mRNA. The synthesis of malic enzyme also was inhibited by glucagon at a pretranslational step, but the inhibition was almost complete. Thus, despite coordinated regulation of the concentrations of these enzymes during starvation and refeeding, individual hormones sometimes regulate synthesis of the two enzymes at the same step and to about the same degree and sometimes at different steps or to very different degrees.
通过比较培养的鸡胚肝细胞中脂肪酸合酶的mRNA水平与酶合成速率，对脂肪酸合酶多激素调节所涉及的机制进行了研究。三碘甲状腺原氨酸或胰岛素可使脂肪酸合酶的相对合成速率增加约2.5倍。这两种激素共同作用具有协同效应，可刺激酶合成增加近40倍（Fischer, P.W.F., and Goodridge, A.G. (1978) Arch. Biochem. Biophys. 190, 332 - 344）。无论是否存在胰岛素，添加三碘甲状腺原氨酸均可刺激mRNA水平升高，且升高程度与酶合成增加程度相当。因此，三碘甲状腺原氨酸主要通过控制其mRNA的量来调节脂肪酸合酶。在存在三碘甲状腺原氨酸的情况下添加胰岛素，可刺激酶合成增加14倍，而mRNA水平仅增加2倍。在不存在三碘甲状腺原氨酸的情况下，胰岛素对mRNA水平无影响。因此，胰岛素对脂肪酸合酶mRNA的翻译有主要作用。添加三碘甲状腺原氨酸后，脂肪酸合酶mRNA呈S形动力学积累，在添加激素后约48小时接近新的稳态。嘌呤霉素是一种蛋白质合成抑制剂，可阻断三碘甲状腺原氨酸的作用。我们认为，脂肪酸合酶和苹果酸酶的mRNA丰度均受一种共同的、由三碘甲状腺原氨酸诱导产生的、半衰期相对较长的肽中间体调节。胰高血糖素可使脂肪酸合酶的合成减少80%（Fischer, P.W.F., and Goodridge, A.G. (1978) Arch. Biochem. Biophys. 190, 332 - 344），并使脂肪酸合酶mRNA水平降低60%。因此，胰高血糖素通过控制其mRNA的浓度来调节脂肪酸合酶。苹果酸酶的合成在翻译前步骤也受到胰高血糖素的抑制，但抑制几乎是完全的。因此，尽管在饥饿和重新进食期间这些酶的浓度受到协调调节，但个别激素有时在同一步骤以大致相同的程度调节这两种酶的合成，有时在不同步骤或以非常不同的程度进行调节。
