Evaluation of inhibition of fatty acid synthase by ursolic acid: positive cooperation mechanism.
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.
Liu
Yang
Y
Graduate University of Chinese Academy of Sciences, Beijing 100049, China.
Tian
Weixi
W
Ma
Xiaofeng
X
Ding
Wenjun
W
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D009249:NADP / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
D000972:Antineoplastic Agents, Phytogenic; D064429:Fatty Acid Synthases; D000960:Hypolipidemic Agents; D009249:NADP; D014315:Triterpenes; D000097245:Ursolic Acid