Agents affecting lipid metabolism. 23. The effect of an inhibitor of cholesterol biosynthesis on the incorporation of precursors of phosphatides in rat serum and tissues.

Abstract

The biosynthesis of phosphatides in rat tissues was investigated with mixtures of choline-Me-14C and palmitic acid-9,10-3H, and dl-serine-3-14C and palmitic acid-9,10-3H respectively. Labeled choline and palmitic acid were incorporated at different rates into N-base and acyl moieties of phosphatides in the tissues, including the brain. Comparison of the specific activity of β-fatty acids of phosphatidyl ethanolamines (PE) and phosphatidyl cholines (PC), labeled with3H derived from palmitic acid, indicated that either the two phosphatides were synthesized from different pools of diglycerides, or that the acyl β-transferases involved in the synthesis of PE and PC had different rates of incorporation.In rats fed a cholesterol biosynthesis inhibitor, AY-9944, the specific activity of β-fatty acids in PE and PC was reduced in the tissues, notably in the lungs. The incorporation of labeled choline was also reduced in the tissues. Except in the lungs, AY-9944 reduced the incorporation of labeled palmitic acid and choline into tissue sphingomyelins to a different degree. Evidence suggested that AY-9944 affected either diglyceride formation or the acyl β-transferases, or both. Furthermore, the alteration in diglyceride, or a more direct effect of AY-9944 on the incorporation of choline via cytidyl phosphorylcholine, resulted in a reduction of incorporation into the N-base moiety.