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This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/E638    most recent 00192.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Rozance, P. J. Articles by Brown, L. D. PubMed PubMed Citation Articles by Rozance, P. J. Articles by Brown, L. D.

Prolonged maternal amino acid infusion in late-gestation pregnant sheep increases fetal amino acid oxidation

¹Perinatal Research Center, Department of Pediatrics, University of Colorado Denver School of Medicine; ²Department of Internal Medicine, University of Colorado Denver School of Medicine, Aurora, Colorado; and ³University of Vermont College of Medicine, Burlington, Vermont

Submitted 24 March 2009 ; accepted in final form 6 July 2009

Protein supplementation during human pregnancy does not improve fetal growth and may increase small-for-gestational-age birth rates and mortality. To define possible mechanisms, sheep with twin pregnancies were infused with amino acids (AA group, n = 7) or saline (C group, n = 4) for 4 days during late gestation. In the AA group, fetal plasma leucine, isoleucine, valine, and lysine concentrations were increased (P < 0.05), and threonine was decreased (P < 0.05). In the AA group, fetal arterial pH (7.365 ± 0.007 day 0 vs. 7.336 ± 0.012 day 4, P < 0.005), hemoglobin-oxygen saturation (46.2 ± 2.6 vs. 37.8 ± 3.6%, P < 0.005), and total oxygen content (3.17 ± 0.17 vs. 2.49 ± 0.20 mmol/l, P < 0.0001) were decreased on day 4 compared with day 0. Fetal leucine disposal did not change (9.22 ± 0.73 vs. 8.09 ± 0.63 µmol·min^–1·kg^–1, AA vs. C), but the rate of leucine oxidation increased 43% in the AA group (2.63 ± 0.16 vs. 1.84 ± 0.24 µmol·min^–1·kg^–1, P < 0.05). Fetal oxygen utilization tended to be increased in the AA group (327 ± 23 vs. 250 ± 29 µmol·min^–1·kg^–1, P = 0.06). Rates of leucine incorporation into fetal protein (5.19 ± 0.97 vs. 5.47 ± 0.89 µmol·min^–1·kg^–1, AA vs. C), release from protein breakdown (4.20 ± 0.95 vs. 4.62 ± 0.74 µmol·min^–1·kg^–1), and protein accretion (1.00 ± 0.30 vs. 0.85 ± 0.25 µmol·min^–1·kg^–1) did not change. Consistent with these data, there was no change in the fetal skeletal muscle ubiquitin ligases MaFBx1 or MuRF1 or in the protein synthesis regulators 4E-BP1, eEF2, eIF2, and p70^S6K. Decreased concentrations of certain essential amino acids, increased amino acid oxidation, fetal acidosis, and fetal hypoxia are possible mechanisms to explain fetal toxicity during maternal amino acid supplementation.

metabolism; threonine; leucine; oxygen