Data recently acquired in our laboratory suggest that several of the metabolic characteristics of the ovine fetus and placenta may be affected, and possibly regulated, by the oxidative catabolism of the branched chain amino acids. Findings which support such a role for branched chain amino acids include: 1) placental utilization of branched chain amino acids which may increase during fasting, 2) placental production of lactate, 3) hind limb uptake of branched chain amino acids which increases during fasting, and 4) hind limb production of alanine and glutamine during fasting. It is possible that the branched chain amino acids may affect fetal/placental metabolism similar to adult metabolism; i.e., by sparing glucose, inhibiting pyruvate oxidation, inhibiting protein breakdown and stimulating protein synthesis. Therefore to characterize how branched chain amino acids and branched chain ketoacids may modulate ovine fetal carbohydratae and amino acid metabolism during normal growth as well as during periods of maternal fasting, the following studies are planned. First, simultaneous determinations of uterine and umbilical uptakes of a variety of substrates will be performed in the same animals in the fed and fasted states. This investigation will precisely quantitate the placental and umbilical balance of the branched chain amino acids, branched chain ketoacids, potential gluconeogenic amino acids and other related substrate. The second phase of investigation will quantitate the distribution and relative activity of the two enzymes required for metabolism of the branched chain amino acids in the placenta, and in several fetal and maternal tissues. The final phase of study will describe the effects of branched chain amino acids and ketoacids on placental metabolism in vitro. A comparison of in vivo with in vitro metabolic parameters will thus be possible.
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| Philipps, A F; Rosenkrantz, T S; Lemons, J A et al. (1990) Insulin-induced alterations in amino acid metabolism in the fetal lamb. J Dev Physiol 13:251-9 |
| Goodwin, G W; Gibboney, W; Paxton, R et al. (1987) Activities of branched-chain amino acid aminotransferase and branched-chain 2-oxo acid dehydrogenase complex in tissues of maternal and fetal sheep. Biochem J 242:305-8 |
