Effects of phosphatidylcholine liposomes on the fatty acid synthetase complex from Mycobacterium smegmatis

Abstract

Phosphatidylcholine liposomes stimulate fatty acid synthesis catalyzed by the multienzyme complex from Mycobacterium smegmatis up to 3-fold and raise the proportion of shorter chain fatty acids (C 14, C 16, C 18) from 15 to 72%. Palmitoyl-CoA in a concentration of 10 μM inhibits the synthetase completely. This inhibition is fully relieved by liposomes. Increasing the incubation temperature from 19 to 45° C, raises the rate of synthesis (2-fold) and the proportion of long chain fatty acids (C 24 and C 26). Liposomes (250 μM) potentiate the effect of temperature on rate by another factor of 2 and have a chain-shortening effect in parallel with increasing temperature. In short term experiments (30 s) an increase in the concentration of acetyl-CoA (from 50 to 1000 μM) does not significantly affect the overall rate of synthesis but it doubles the percentage of short chain fatty acids. Under these conditions there is no superimposed liposome effect either on rate or product distribution. During longer periods (15 min) the overall rate increases as a function of acetyl-CoA concentration. This rate increase is enhanced by liposomes. At the same time, liposomes substantially raise the percentage of short chain acids. It is concluded that liposomes affect the de novo synthesis rate by alleviating feedback inhibition of the synthetase caused by C 16- and C 18-CoA. By sequestering these products, liposomes minimize the further elongation of C 16 chains. The possible role of membrane phospholipids in controlling the rate of synthesis and the length of fatty acid chains is discussed.