Amino acid modulation of renal phosphatidylcholine biosynthesis in the rat

The hypothesis that amino acids act as modifiers of phospholipid biosynthesis was tested in renal cortical cells from normal rats. The rate of [14C]-choline incorporation into phospholipid in cortical slices was enhanced by the addition of lysine or arginine to the incubation medium, and reduced by phenylalanine, aspartic acid, or four other amino acids. Lysine and aspartic acid appeared to modify the cholinephosphotransferase reaction in which cytidine 5'-diphosphocholine (CDP-choline) and 1,2-diacylglycerol react to form phosphatidylcholine, the major phospholipid of renal membranes. Since this enzymatic reaction takes place in the endoplasmic reticulum, the effect of single amino acids on microsomal preparations was examined. Lysine increased CDP-choline:1,2-diacylglycerol cholinephosphotransferase activity by 95%, whereas aspartic acid reduced activity by 65%, in a concentration-dependent manner. For both substrates in the reaction, amino acids modulated enzyme activity by altering the maximum velocity without changing the apparent Km. These observations in intact renal cells and in microsomal preparations indicate that changes in cellular amino acid concentrations could modify the biosynthetic rate of phosphatidylcholine, and suggest a mechanism that could coordinate the biosynthesis of phospholipid and protein.