Phenylbutyrate improves nitrogen disposal via an alternative pathway without eliciting an increase in protein breakdown and catabolism in control and ornithine transcarbamylase-deficient patients

American Journal of Clinical Nutrition

Volumn 93, Issue 6, 2011, Pages 1248-1254

  Marini, Juan C ^a   Lanpher, Brendan C ^a   Scaglia, Fernando ^a   O'Brien, William E ^a   Sun, Qin ^a   Garlick, Peter J ^c   Jahoor, Farook ^a   Lee, Brendan ^a,b  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^c UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 PHENYLBUTYRIC ACID; 5 GLUTAMINE N 15; [RING 3,5 D 2]TYROSINE; [RING D 5]PHENYLALANINE; BRANCHED CHAIN AMINO ACID; CITRULLINE; GLUTAMINE; ISOLEUCINE; LEUCINE; LEUCINE C 13; NITROGEN; NITROGEN 15; PHENYLALANINE; RADIOISOTOPE; TYROSINE; UNCLASSIFIED DRUG; UREA; UREA C 13 O 18; VALINE;

ADOLESCENT; ADULT; AGED; AMINO ACID TRANSPORT; ARTICLE; CHILD; CLINICAL ARTICLE; CONTINUOUS INFUSION; CONTROLLED STUDY; DISEASE CONTROL; DRUG EFFECT; FEMALE; HUMAN; MALE; ORNITHINE TRANSCARBAMYLASE DEFICIENCY; PRESCHOOL CHILD; PROTEIN DEGRADATION; PROTEIN DEPLETION; PROTEIN METABOLISM; SCHOOL CHILD; UREA CYCLE;

ADOLESCENT; ADULT; AGED; AMINO ACIDS; AMINO ACIDS, BRANCHED-CHAIN; CHILD; FEMALE; GLUTAMINE; HUMANS; MALE; METABOLIC NETWORKS AND PATHWAYS; MIDDLE AGED; NITROGEN; ORNITHINE CARBAMOYLTRANSFERASE DEFICIENCY DISEASE; PHENYLBUTYRATES; PROTEINS; UREA; YOUNG ADULT;

EID: 79956307866     PISSN: 00029165     EISSN: 19383207     Source Type: Journal    
DOI: 10.3945/ajcn.110.009043     Document Type: Article

References (25)

1. Batshaw ML, MacArthur RB, Tuchman M. Alternative pathway therapy for urea cycle disorders: twenty years later. J Pediatr 2001;138:S46-54.
2. Brusilow SW. Phenylacetylglutamine may replace urea as a vehicle for waste nitrogen excretion. Pediatr Res 1991;29:147-50.
3. Burlina AB, Ogier H, Korall H, Trefz FK. Long-term treatment with sodium phenylbutyrate in ornithine transcarbamylase-deficient patients. Mol Genet Metab 2001;72:351-5. (Pubitemid 34171431)
4. James MO, Smith RL, Williams RT, Reidenberg M. The conjugation of phenylacetic acid in man, sub-human primates and some non-primate species. Proc R Soc Lond B Biol Sci 1972;182:25-35.
5. Moldave K, Meister A. Synthesis of phenylacetylglutamine by human tissue. J Biol Chem 1957;229:463-76.
6. Kasumov T, Brunengraber LL, Comte B, et al. New secondary metabolites of phenylbutyrate in humans and rats. Drug Metab Dispos 2004;32:10-9. (Pubitemid 38112530)
7. Gore SD, Samid D, Weng LJ. Impact of the putative differentiating agents sodium phenylbutyrate and sodium phenylacetate on proliferation, differentiation, and apoptosis of primary neoplastic myeloid cells. Clin Cancer Res 1997;3:1755-62. (Pubitemid 27444714)
8. Sawatsri S, Samid D, Malkapuram S, Sidell N. Inhibition of estrogen-dependent breast cell responses with phenylacetate. Int J Cancer 2001;93:687-92. (Pubitemid 32695117)
9. Shama Bhat C, Ramasarma T. Inhibition of rat liver mevalonate pyrophosphate decarboxylase and mevalonate phosphate kinase by phenyl and phenolic compounds. Biochem J 1979;181:143-51. (Pubitemid 9236525)
10. Kern RM, Yang Z, Kim PS, Grody WW, Iyer RK, Cederbaum SD. Arginase induction by sodium phenylbutyrate in mouse tissues and human cell lines. Mol Genet Metab 2007;90:37-41. (Pubitemid 44856286)
11. Praphanphoj V, Boyadjiev SA, Waber LJ, Brusilow SW, Geraghty MT. Three cases of intravenous sodium benzoate and sodium phenylacetate toxicity occurring in the treatment of acute hyperammonaemia. J Inherit Metab Dis 2000;23:129-36. (Pubitemid 30198115)
12. Darmaun D, Welch S, Rini A, Sager BK, Altomare A, Haymond MW. Phenylbutyrate-induced glutamine depletion in humans: effect on leucine metabolism. Am J Physiol 1998;274:E801-7.
13. Le Bacquer O, Mauras N, Welch S, Haymond M, Darmaun D. Acute depletion of plasma glutamine increases leucine oxidation in prednisone-treated humans. Clin Nutr 2007;26:231-8. (Pubitemid 46504826)
14. Scaglia F, Carter S, O'Brien WE, Lee B. Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients. Mol Genet Metab 2004;81(suppl 1):S79-85.
15. Waldegger S, Busch GL, Kaba NK, et al. Effect of cellular hydration on protein metabolism. Miner Electrolyte Metab 1997;23:201-5. (Pubitemid 27475345)
16. Matthews DE. Observations of branched-chain amino acid administration in humans. J Nutr 2005;135:1580S-4S.
17. Garlick PJ. The role of leucine in the regulation of protein metabolism. J Nutr 2005;135:1553S-6S.
18. 5]phenylalanine model. Am J Physiol 1989;256:E631-9.
19. Piscitelli SC, Thibault A, Figg WD, et al. Disposition of phenylbutyrate and its metabolites, phenylacetate and phenylacetylglutamine. J Clin Pharmacol 1995;35:368-73.
20. Bergstrom J, Furst P, Noree LO, Vinnars E. Intracellular free amino acid concentration in human muscle tissue. J Appl Physiol 1974;36:693-7.
21. Rouge C, Des Robert C, Robins A, et al. Manipulation of citrulline availability in humans. Am J Physiol 2007;293:G1061-7.
22. Tuchman M, Lee B, Lichter-Konecki U, et al. Cross-sectional multicenter study of patients with urea cycle disorders in the United States. Mol Genet Metab 2008;94:397-402.
23. Stipanuk MH. Leucine and protein synthesis: mTOR and beyond. Nutr Rev 2007;65:122-9.
24. Lee B, Singh RH, Rhead WJ, King LS, Smith W, Summar ML. Considerations in the difficult-to-manage urea cycle disorder patient. Crit Care Clin 2005;21(4 suppl):S19-25.
25. Brunetti-Pierri N, Lanpher B, Erez A, et al. Phenylbutyrate therapy for maple syrup urine disease. Hum Mol Genet 2011;20:631-40.