Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 6/1/2007
Publication Date: 9/1/2007
Citation: Marini, J.C., Lanpher, B., Scaglia, F., Carter, S., Garlick, P.J., Jahoor, F., Lee, B. 2007. Phenylbutyrate reduces plasma leucine concentrations without affecting the flux of leucine [abstract]. FASEB Journal. 21:A335. Interpretive Summary:
Technical Abstract: Phenylbutyrate (PB) has been used as an alternative pathway to excrete nitrogen in urea cycle disorder patients for the last 20 years. PB, after oxidation to phenylacetate, is conjugated with glutamine and excreted in the urine. A reduction in the plasma concentration of branched amino acids (BCAA) has been observed in subjects on PB medication. This has raised concerns regarding amino acid homeostasis on medicated patients. The present study was conducted to investigate the effect of PB (0 or 0.5 g kg-1 BW) on leucine, glutamine and urea kinetics in 7 control subjects utilizing a multi-tracer protocol. After 2 days of constant protein intake (0.6 g kg-1d-1), subjects were fed every 2 h during the 10-h infusion to achieve steady state conditions. Urea production was reduced when the subjects were on PB (156 vs. 180+/-11 µmol kg-1 h-1, P<0.04) as well as the transfer of 15N from infused glutamine (11.0 vs. 16.8+/-0.70 %). However, no changes in glutamine fluxes were evident. No difference (P>0.15) in the entry rate of leucine, phenylalanine, or tyrosine, nor in CO2 production resulted from PB treatment. Plasma leucine concentrations were lower in subjects on PB during fasting (64 vs. 104 µmol/L, P<0.01) and when fed (106 vs. 146 µmol/L, P<0.01). Isoleucine and valine behaved similarly, while other indispensable amino acids showed no differences between treatments. PB affected neither amino acid fluxes nor proteolysis, despite reduced concentration in circulating BCAA.