Systemic arginine depletion: effects on protein synthesis and blood pressure in mice (258.4)

Arginine (Arg) is a semi‐essential amino acid involved in protein synthesis (PS) and blood pressure (BP) regulation. Arg deiminase (ADI) is a bacterial enzyme that hydrolyses Arg imino group to yield citrulline (Cit) and NH 3 . Pegylated ADI (ADI‐PEG) administration in animals and humans results in the depletion of circulating Arg. To investigate the effect of ADI‐PEG on PS and BP, ADI‐PEG or Saline (Sal) were administered i.m. to male mice. Plasma Arg concentration was negligible (<1; Sal 80 µmol/L), but Cit increased several fold (1100; Sal 80 µmol/L) in ADI‐PEG treated mice. Arg and Cit fluxes were greater in ADI‐PEG mice (Arg 543 vs 910, Cit 126 vs 402 µmol•kg ‐1 •h ‐1 , Sal and ADI‐PEG, resp.). The conversion of Arg to Cit, usually used as a proxy for NO production, increased from 4.1 to 496 µmol•kg ‐1 •h ‐1 , demonstrating the activity of the deiminase. Phenylalanine and tyrosine fluxes and phenylalanine hydroxylation were not different between the two treatments, indicating no changes in whole body protein kinetics. Protein fractional synthesis rate was not different for most tissues, but it was lower in the brain, thymus and testicles of ADI‐PEG treated mice. 14 C Cit incorporation showed an identical pattern. Mean BP was reduced in ADI‐PEG treated mice (105 vs Sal 118 mm Hg, P< 0.008), despite the virtual absence of Arg in blood. These results demonstrate the capacity of many cell types to derive ARG from Cit to meet their needs. Grant Funding Source : Supported by USDA/ARS Cooperative Agreement No 58‐6250‐6‐001