Graduate University of Chinese Academy of Sciences, Beijing 100049, China.
Biochem Biophys Res Commun. 2010 Feb 12;392(3):386-90. doi: 10.1016/j.bbrc.2010.01.031. Epub 2010 Jan 13.
The inhibitory effect of ursolic acid (UA) on fatty acid synthase (FAS, EC 2.3.1.85) was investigated. We found that UA potently inhibited the activity of FAS with a half-inhibitory concentration value (IC(50)) of 6.0 microg/ml. The inhibition kinetic results showed that the inhibition of FAS by UA was competitive against acetyl-CoA and malonyl-CoA, but uncompetitive to NADPH. UA at low concentration slowly inactivated FAS, but FAS was fast inactivated by high concentration of UA in a positive cooperative manner. Moreover, NADPH significantly enhanced the inactivation of FAS by low concentration of UA, but NADPH slightly decreased the inactivation of FAS by high concentration of UA. Taken together, the results suggest that ursolic acid decreases the FAS activity through inactivation of acetyl/malonyl transferase. The combination of NADPH and KR domain promotes the inhibitory effect of UA on FAS.
我们研究了熊果酸（UA）对脂肪酸合酶（FAS，EC 2.3.1.85）的抑制作用。结果发现 UA 能强烈抑制 FAS 的活性，其半数抑制浓度（IC50）值为 6.0μg/ml。抑制动力学研究结果表明，UA 对 FAS 的抑制作用是对乙酰辅酶 A 和丙二酰辅酶 A 的竞争性抑制，而对 NADPH 是非竞争性抑制。低浓度的 UA 可使 FAS 缓慢失活，而高浓度的 UA 则以正协同方式快速失活 FAS。此外，NADPH 能显著增强低浓度 UA 对 FAS 的失活作用，而 NADPH 则略微降低高浓度 UA 对 FAS 的失活作用。综上所述，这些结果提示熊果酸通过抑制乙酰基/丙二酰基转移酶降低 FAS 的活性。NADPH 和 KR 结构域的结合促进了 UA 对 FAS 的抑制作用。
