Glutamate may play an important role in integrating the metabolic activity of the placenta and the fetal liver. Studies in fetal lambs have demonstrated a large net flow of glutamate from the fetus to the placenta and in opposite direction to a large net flow of glutamine from placenta to fetus. The fetal liver shows the reverse, i.e., net glutamate output and net glutamine uptake. To clarify the physiological meaning of these observations, experiments will be performed in fetal lambs under normal physiologic conditions using both stable isotope tracers and 14C labelled glutamate. The tracers will be infused in either the fetus, the mother or both for the purpose of measuring (1) the disposal rate of fetal plasma glutamate, its uptake by the placenta, its decarboxylation rate and conversion to glutamine in both fetus and placenta, (2) the disposal rate of fetal plasma glutamine and its conversion to fetal plasma glutamate by the whole fetus and by the fetal liver, (3) the entry rate of maternal glutamate and/or products of its placental metabolism into the fetal circulation, (4) the entry rate of maternal glutamine into the fetal plasma glutamine pool and (5) the effect of increasing the supply of fetal glutamate to the placenta on the placental uptake and metabolism of fetal glutamate, and on placental 02 consumption rate.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD029374-03
Application #
2201775
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1992-08-01
Project End
1996-07-31
Budget Start
1994-08-01
Budget End
1996-07-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Physiology
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Timmerman, M; Wilkening, R B; Regnault, T R H (2003) Induction of glutamate dehydrogenase in the ovine fetal liver by dexamethasone infusion during late gestation. Exp Biol Med (Maywood) 228:100-5
Timmerman, M; Teng, C; Wilkening, R B et al. (2001) Net amino acid flux across the fetal liver and placenta during spontaneous ovine parturition. Biol Neonate 79:54-60
Timmerman, M; Teng, C; Wilkening, R B et al. (2000) Effect of dexamethasone on fetal hepatic glutamine-glutamate exchange. Am J Physiol Endocrinol Metab 278:E839-45
Holcomb, R G; Wilkening, R B (1999) Fetal hepatic oxygen consumption under normal conditions in the fetal lamb. Biol Neonate 75:310-8
Jozwik, M; Teng, C; Battaglia, F C et al. (1999) Fetal supply of amino acids and amino nitrogen after maternal infusion of amino acids in pregnant sheep. Am J Obstet Gynecol 180:447-53
Jozwik, M; Teng, C; Meschia, G et al. (1999) Contribution of branched-chain amino acids to uteroplacental ammonia production in sheep. Biol Reprod 61:792-6
Chung, M; Teng, C; Timmerman, M et al. (1998) Production and utilization of amino acids by ovine placenta in vivo. Am J Physiol 274:E13-22
Barbera, A; Wilkening, R B; Teng, C et al. (1997) Metabolic alterations in the fetal hepatic and umbilical circulations during glucocorticoid-induced parturition in sheep. Pediatr Res 41:242-8
Vaughn, P R; Lobo, C; Battaglia, F C et al. (1995) Glutamine-glutamate exchange between placenta and fetal liver. Am J Physiol 268:E705-11
Moores Jr, R R; Vaughn, P R; Battaglia, F C et al. (1994) Glutamate metabolism in fetus and placenta of late-gestation sheep. Am J Physiol 267:R89-96