Amino acid-mediated stimulation of renal phospholipid biosynthesis after acute tubular necrosis

Abstract

The mechanism by which amino acid infusion stimulates membrane physpholipid biosynthesis during renal regeneration after mercuric-chloride-induced acute tubular necrosis was studied in the rat. Amino acids can act directly on regenerating renal tissue to enhance net phospholipid synthesis because preincubation of cortical slices with amino acids induced an increase in [14C]-choline incorporation into phospholipid without altering the rate of breakdown. This amino acid stimulation of phospholipid biosynthesis was studied further by measuring [14C]-choline accumulation and its sequential conversion to phosphorylcholine, cytidine diphosphocholine (CDP-choline), and phosphatidylcholine via the Kennedy pathway in regenerating renal tissue. [14C]-Choline accumulation was increased after amino acid infusion, compared to glucose infusion. There were also increments in the Vmax of the choline kinase reaction, which converts entering [14C]-choline into [14C]-phosphorylcholine, and of the cholinephosphotransferase reaction in which [14C]-CDP-choline is incorporated into [14C]-phosphatidylcholine, whereas the apparent Km of each reaction was unchanged. Thus, amino acids infused after tubular necrosis can act directly on regenerating renal cells to increase precursor availability and augment two reactions of the phospholipid biosynthetic pathway.