Abstract | BACKGROUND: Phenylbutyrate is a drug used in patients with urea cycle disorder to elicit alternative pathways for nitrogen disposal. However, phenylbutyrate administration decreases plasma branched-chain amino acid (BCAA) concentrations, and previous research suggests that phenylbutyrate administration may increase leucine oxidation, which would indicate increased protein degradation and net protein loss. OBJECTIVE: DESIGN: Seven healthy control and 7 partial-OTCD subjects received either phenylbutyrate or no treatment in a crossover design. In addition, the partial-OTCD and 3 null-OTCD subjects received phenylbutyrate and phenylbutyrate plus BCAA supplementation. A multitracer protocol was used to determine the whole-body fluxes of urea and amino acids of interest. RESULTS: Phenylbutyrate administration reduced ureagenesis by ≈15% without affecting the fluxes of leucine, tyrosine, phenylalanine, or glutamine and the oxidation of leucine or phenylalanine. The transfer of (15)N from glutamine to urea was reduced by 35%. However, a reduction in plasma concentrations of BCAAs due to phenylbutyrate treatment was observed. BCAA supplementation did not alter the respective baseline fluxes. CONCLUSIONS: Prolonged phenylbutyrate administration reduced ureagenesis and the transfer of (15)N from glutamine to urea without parallel reductions in glutamine flux and concentration. There were no changes in total-body protein breakdown and amino acid catabolism, which suggests that phenylbutyrate can be used to dispose of nitrogen effectively without adverse effects on body protein economy.
|
Authors | Juan C Marini, Brendan C Lanpher, Fernando Scaglia, William E O'Brien, Qin Sun, Peter J Garlick, Farook Jahoor, Brendan Lee |
Journal | The American journal of clinical nutrition
(Am J Clin Nutr)
Vol. 93
Issue 6
Pg. 1248-54
(Jun 2011)
ISSN: 1938-3207 [Electronic] United States |
PMID | 21490144
(Publication Type: Controlled Clinical Trial, Journal Article, Research Support, N.I.H., Extramural)
|
Chemical References |
- Amino Acids
- Amino Acids, Branched-Chain
- Phenylbutyrates
- Proteins
- Glutamine
- Urea
- Nitrogen
|
Topics |
- Adolescent
- Adult
- Aged
- Amino Acids
(metabolism, pharmacology)
- Amino Acids, Branched-Chain
(blood, pharmacology)
- Child
- Female
- Glutamine
(metabolism)
- Humans
- Male
- Metabolic Networks and Pathways
(drug effects)
- Middle Aged
- Nitrogen
(metabolism)
- Ornithine Carbamoyltransferase Deficiency Disease
(drug therapy, metabolism)
- Phenylbutyrates
(pharmacology, therapeutic use)
- Proteins
(metabolism)
- Urea
(metabolism)
- Young Adult
|