Abstract
To determine to what extent intravenous nutrition can reduce proteolysis in very immature and normal newborns, and to assess the capacity of preterm and normal newborns to convert phenylalanine to tyrosine, phenylalanine and leucine kinetics were measured under basal conditions and during parenteral nutrition in clinically stable, extremely premature (approximately 26 wk of gestation) infants and in normal term newborns. In response to parenteral nutrition, there was significantly less suppression (P < 0.001) of endogenous leucine and phenylalanine rate of appearance in extremely premature infants compared with term infants. Phenylalanine utilization for protein synthesis during parenteral nutrition increased significantly (P < 0.01) and by the same magnitude (approximately 15%) in both extremely premature and term infants. Phenylalanine was converted to tyrosine at substantial rates in both extremely premature and term infants; however, this conversion rate was significantly higher (P < 0.05) in extremely premature infants during both the basal and parenteral nutrition periods. These data provide clear evidence that there is no immaturity in the phenylalanine hydroxylation pathway. Furthermore, although parenteral nutrition appears to produce similar increases in protein synthesis in extremely premature and term infants, proteolysis is suppressed much less in extremely premature newborns. The factors responsible for this apparent resistance to suppression of proteolysis in the very immature newborn remain to be elucidated.
Full Text
The Full Text of this article is available as a PDF (206.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Beaufrère B., Chassard D., Broussolle C., Riou J. P., Beylot M. Effects of D-beta-hydroxybutyrate and long- and medium-chain triglycerides on leucine metabolism in humans. Am J Physiol. 1992 Mar;262(3 Pt 1):E268–E274. doi: 10.1152/ajpendo.1992.262.3.E268. [DOI] [PubMed] [Google Scholar]
- Bier D. M. Intrinsically difficult problems: the kinetics of body proteins and amino acids in man. Diabetes Metab Rev. 1989 Mar;5(2):111–132. doi: 10.1002/dmr.5610050203. [DOI] [PubMed] [Google Scholar]
- Biolo G., Tessari P., Inchiostro S., Bruttomesso D., Fongher C., Sabadin L., Fratton M. G., Valerio A., Tiengo A. Leucine and phenylalanine kinetics during mixed meal ingestion: a multiple tracer approach. Am J Physiol. 1992 Apr;262(4 Pt 1):E455–E463. doi: 10.1152/ajpendo.1992.262.4.E455. [DOI] [PubMed] [Google Scholar]
- Castellino P., Luzi L., Simonson D. C., Haymond M., DeFronzo R. A. Effect of insulin and plasma amino acid concentrations on leucine metabolism in man. Role of substrate availability on estimates of whole body protein synthesis. J Clin Invest. 1987 Dec;80(6):1784–1793. doi: 10.1172/JCI113272. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Denne S. C., Kalhan S. C. Leucine metabolism in human newborns. Am J Physiol. 1987 Dec;253(6 Pt 1):E608–E615. doi: 10.1152/ajpendo.1987.253.6.E608. [DOI] [PubMed] [Google Scholar]
- Denne S. C., Karn C. A., Wang J., Liechty E. A. Effect of intravenous glucose and lipid on proteolysis and glucose production in normal newborns. Am J Physiol. 1995 Aug;269(2 Pt 1):E361–E367. doi: 10.1152/ajpendo.1995.269.2.E361. [DOI] [PubMed] [Google Scholar]
- Denne S. C., Liechty E. A., Liu Y. M., Brechtel G., Baron A. D. Proteolysis in skeletal muscle and whole body in response to euglycemic hyperinsulinemia in normal adults. Am J Physiol. 1991 Dec;261(6 Pt 1):E809–E814. doi: 10.1152/ajpendo.1991.261.6.E809. [DOI] [PubMed] [Google Scholar]
- Flakoll P. J., Kulaylat M., Frexes-Steed M., Hourani H., Brown L. L., Hill J. O., Abumrad N. N. Amino acids augment insulin's suppression of whole body proteolysis. Am J Physiol. 1989 Dec;257(6 Pt 1):E839–E847. doi: 10.1152/ajpendo.1989.257.6.E839. [DOI] [PubMed] [Google Scholar]
- Goldspink D. F., Kelly F. J. Protein turnover and growth in the whole body, liver and kidney of the rat from the foetus to senility. Biochem J. 1984 Jan 15;217(2):507–516. doi: 10.1042/bj2170507. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hertz D. E., Karn C. A., Liu Y. M., Liechty E. A., Denne S. C. Intravenous glucose suppresses glucose production but not proteolysis in extremely premature newborns. J Clin Invest. 1993 Oct;92(4):1752–1758. doi: 10.1172/JCI116763. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jakubovic A. Phenylalanine-hydroxylating system in the human fetus at different developmental ages. Biochim Biophys Acta. 1971 Jun 22;237(3):469–475. doi: 10.1016/0304-4165(71)90265-0. [DOI] [PubMed] [Google Scholar]
- Louard R. J., Barrett E. J., Gelfand R. A. Effect of infused branched-chain amino acids on muscle and whole-body amino acid metabolism in man. Clin Sci (Lond) 1990 Nov;79(5):457–466. doi: 10.1042/cs0790457. [DOI] [PubMed] [Google Scholar]
- Melville S., McNurlan M. A., McHardy K. C., Broom J., Milne E., Calder A. G., Garlick P. J. The role of degradation in the acute control of protein balance in adult man: failure of feeding to stimulate protein synthesis as assessed by L-[1-13C]leucin infusion. Metabolism. 1989 Mar;38(3):248–255. doi: 10.1016/0026-0495(89)90083-8. [DOI] [PubMed] [Google Scholar]
- Mitton S. G., Calder A. G., Garlick P. J. Protein turnover rates in sick, premature neonates during the first few days of life. Pediatr Res. 1991 Nov;30(5):418–422. doi: 10.1203/00006450-199111000-00005. [DOI] [PubMed] [Google Scholar]
- Moldawer L. L., Kawamura I., Bistrian B. R., Blackburn G. L. The contribution of phenylalanine to tyrosine metabolism in vivo. Studies in the post-absorptive and phenylalanine-loaded rat. Biochem J. 1983 Mar 15;210(3):811–817. doi: 10.1042/bj2100811. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nair K. S., Ford G. C., Ekberg K., Fernqvist-Forbes E., Wahren J. Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients. J Clin Invest. 1995 Jun;95(6):2926–2937. doi: 10.1172/JCI118000. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nair K. S., Matthews D. E., Welle S. L., Braiman T. Effect of leucine on amino acid and glucose metabolism in humans. Metabolism. 1992 Jun;41(6):643–648. doi: 10.1016/0026-0495(92)90057-h. [DOI] [PubMed] [Google Scholar]
- Pereira G. R. Nutritional care of the extremely premature infant. Clin Perinatol. 1995 Mar;22(1):61–75. [PubMed] [Google Scholar]
- Rivera A., Jr, Bell E. F., Bier D. M. Effect of intravenous amino acids on protein metabolism of preterm infants during the first three days of life. Pediatr Res. 1993 Feb;33(2):106–111. doi: 10.1203/00006450-199302000-00003. [DOI] [PubMed] [Google Scholar]
- Robert J. J., Bier D. M., Zhao X. H., Matthews D. E., Young V. R. Glucose and insulin effects on the novo amino acid synthesis in young men: studies with stable isotope labeled alanine, glycine, leucine, and lysine. Metabolism. 1982 Dec;31(12):1210–1218. doi: 10.1016/0026-0495(82)90006-3. [DOI] [PubMed] [Google Scholar]
- Räihä N. C. Phenylalanine hydoxylase in human liver during development. Pediatr Res. 1973 Jan;7(1):1–4. doi: 10.1203/00006450-197301000-00001. [DOI] [PubMed] [Google Scholar]
- STEELE R. Influences of glucose loading and of injected insulin on hepatic glucose output. Ann N Y Acad Sci. 1959 Sep 25;82:420–430. doi: 10.1111/j.1749-6632.1959.tb44923.x. [DOI] [PubMed] [Google Scholar]
- Schwenk W. F., Beaufrere B., Haymond M. W. Use of reciprocal pool specific activities to model leucine metabolism in humans. Am J Physiol. 1985 Dec;249(6 Pt 1):E646–E650. doi: 10.1152/ajpendo.1985.249.6.E646. [DOI] [PubMed] [Google Scholar]
- Schwenk W. F., Berg P. J., Beaufrere B., Miles J. M., Haymond M. W. Use of t-butyldimethylsilylation in the gas chromatographic/mass spectrometric analysis of physiologic compounds found in plasma using electron-impact ionization. Anal Biochem. 1984 Aug 15;141(1):101–109. doi: 10.1016/0003-2697(84)90431-7. [DOI] [PubMed] [Google Scholar]
- Shiman R., Jones S. H., Gray D. W. Mechanism of phenylalanine regulation of phenylalanine hydroxylase. J Biol Chem. 1990 Jul 15;265(20):11633–11642. [PubMed] [Google Scholar]
- Tessari P., Biolo G., Inchiostro S., Orlando R., Vettore M., Sergi G. Leucine and phenylalanine kinetics in compensated liver cirrhosis: effects of insulin. Gastroenterology. 1993 Jun;104(6):1712–1721. doi: 10.1016/0016-5085(93)90650-2. [DOI] [PubMed] [Google Scholar]
- Thompson G. N., Pacy P. J., Merritt H., Ford G. C., Read M. A., Cheng K. N., Halliday D. Rapid measurement of whole body and forearm protein turnover using a [2H5]phenylalanine model. Am J Physiol. 1989 May;256(5 Pt 1):E631–E639. doi: 10.1152/ajpendo.1989.256.5.E631. [DOI] [PubMed] [Google Scholar]
- Tserng K. Y., Kalhan S. C. Calculation of substrate turnover rate in stable isotope tracer studies. Am J Physiol. 1983 Sep;245(3):E308–E311. doi: 10.1152/ajpendo.1983.245.3.E308. [DOI] [PubMed] [Google Scholar]