EFFECT OF MEMBRANE ENVIRONMENT ON THE ACTIVITY AND INHIBITABILITY BY MALONYL-COA OF THE CARNITINE ACYLTRANSFERASE OF HEPATIC-MICROSOMAL MEMBRANES

We have investigated the extent to which membrane environment affects the catalytic properties of the malonyl-CoA-sensitive carnitine acyltr ansferase of liver microsomal membranes. Arrhenius-type plots of activ ity were linear in the absence and presence of malonyl-CoA (2.5 mu M) Sensitivity to malonyl-CoA increased with decreasing assay temperature . Partly purified enzyme displayed an increased K-0.5 (substrate conce ntration supporting half the maximal reaction rate) for myristoyl-CoA and a reduced sensitivity to malonyl-CoA compared with the enzyme in s itu in membranes. Reconstitution with liposomes of a range of composit ions restored the K-0.5 for myristoyl-CoA to values similar to that se en in native membranes. The lipid requirements for restoration of sens itivity to malonyl-CoA were more stringent. When animals were starved for 24 h the specific activity of carnitine acyltransferase in microso mal membrane residues was increased 3.3-fold, whereas sensitivity to m alonyl-CoA was decreased to 1/2.8. When enzymes partly purified from f ed and starved animals were reconstituted into crude soybean phosphati dylcholine liposomes there was no difference in sensitivity to malonyl -CoA. When partly purified enzyme from fed rats was reconstituted into liposomes prepared from microsomal membrane lipids from fed animals i t was 2.2-fold more sensitive to malonyl-CoA than when reconstituted w ith liposomes prepared from microsomal membrane lipids from starved an imals. This suggests that the physiological changes in sensitivity to malonyl-CoA are mediated via changes in membrane lipid composition rat her than via modification of the enzyme protein itself. The increased specific activity of acyltransferase observed on starvation could not be attributed to changes in membrane lipid composition.