The inhibitory effect of ursolic acid (UA) oil 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 (IC50) of 60 mu g/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 (C) 2010 Elsevier Inc All rights reserved