Preventive effect of clofibrate on carnitine palmitoyltransferase I inhibition and mitochondrial membrane phospholipid depletion induced by galactosamine.

We have previously reported that a D-galactosamine injection induces a decrease of carnitine palmitoyltransferase I activity correlated with a depletion of total phospholipid content in the mitochondrial membrane. The impact of a short-term clofibrate treatment on these membrane alterations is investigated, i.e., the kinetic properties of carnitine palmitoyltransferase I, including its sensitivity to malonyl-CoA and mitochondrial membrane content of the various phospholipids. A 4-day clofibrate treatment increases by 42% the apparent Km value of carnitine palmitoyltransferase I for palmitoyl-CoA, while the sensitivity of the enzyme to malonyl-CoA appears slightly decreased. Simultaneously, the cardiolipin content is increased by 70% in the mitochondrial membrane, whereas the phosphatidylethanolamine and phosphatidylcholine contents remain almost unaffected. This 4-day clofibrate treatment prevents the inhibition of carnitine palmitoyltransferase I activity subsequent to galactosamine administration but induces an increase in the apparent Km value for palmitoyl-CoA and a decrease of the sensitivity of the enzyme to malonyl-CoA. The contents of phospholipids which are decreased by galactosamine (phosphatidylcholine, -21%; phosphatidylethanolamine, -29%; cardiolipin, -40%) regain the control values when galactosamine administration is preceded by a clofibrate treatment. The data suggest that the clofibrate treatment counteracts the inhibition of activity of carnitine palmitoyltransferase I through the maintenance of mitochondrial membrane integrity.