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

Amino acid-mediated stimulation of renal phospholipid biosynthesis after acute tubular necrosis. The mechanism by which amino acid infusion stimulates membrane phospholipid 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 [ 14 C]-choline incorporation into phospholipid without altering the rate of breakdown. This amino acid stimulation of phospholipid biosynthesis was studied further by measuring [ 14 C]-choline accumulation and its sequential conversion to phosphorylcholine, cytidine diphosphocholine (CDP-choline), and phosphatidylcholine via the Kennedy pathway in regenerating renal tissue. [ 14 C]-Choline accumulation was increased after amino acid infusion, compared to glucose infusion. There were also increments in the V max of the choline kinase reaction, which converts entering [ 14 C]-choline into [ 14 C]-phosphorylcholine, and of the cholinephosphotransferase reaction in which [ 14 C]-CDP-choline is incorporated into [ 14 C]-phosphatidylcholine, whereas the apparent K m 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 bio-synthetic pathway. Stimulation par les acides amines de la biosynthese renale de phospholipides apres necrose tubulaire aigue. Le mecanisme par lequel la perfusion d'acides amines stimule la biosynthese de phospholipides membranaires au cours de la regeneration renale consecutive a la necrose tubulaire aigue determinee par le chlorure mercurique a ete etudie chez le rat. Les acides amines peuvent agir directement sur le tissu renal en regeneration pour accroitre la synthese nette de phospholipides puisque la pre-incubation de tranches de cortex avec des acides amines determine une augmentation de l'incorporation de [ 14 C]-choline dans les phospholipides sans modification du catabolisme. Cette stimulation par les acides amines de la synthese des phospholipides a ete etudiee par la mesure de l'accumulation de [ 14 C]-choline et de sa conversion sequentielle en phosphorylcholine, cytidine diphosphocholine (CDP-choline) et phosphatidylcholine, selon la voie de Kennedy, dans le tissu renal en cours de regeneration. L'accumulation de [ 14 C]-choline est augmentee apres perfusion d'acides amines, par comparaison avec celle de glucose. On observe aussi des augmentations des V max de la reaction de la choline kinase, qui transforme la [ 14 C]-choline entrante en [ 14 C]-phosphorylcholine, et de la reaction de la cholinephosphotransferase, dans laquelle la [ 14 C]-CDP-choline est incorporee dans la [ 14 C]-phosphatidylcholine, alors que le K m de ces reactions est inchange. Ainsi les acides amines perfuses apres une necrose tubulaire peuvent agir directement sur les cellules renales en regeneration pour augmenter la disponibilite en precurseur et accelerer deux reactions de la voie de biosynthese des phospholipides.