These studies will examine the fetal and placental metabolism of two amino acids: 1) an essential amino acid, threonine and 2) alanine. Both are potential glucose precursors. The studies will compare their rates of supply to the fetus and placenta with the fetal and placental requirements. The studies will be carried out in chronically catheterized pregnant sheep, studied under steady state unstressed conditions. Multiple tracer methodology will be used to study their metabolism in fetuses in which placental, fetal and fetal hepatic metabolism can be separated. The oxidation rate, plasma disposal rates and net hepatic uptake and metabolism of these amino acids will be studied under normal conditions and in two different models associated with intrauterine growth retardation, one associated with reduced glucose delivery to the fetus and glucogenesis and the other with normal glucose delivery. Net tracer and tracee fluxes will be measured into and out of the fetus, the fetal liver and the uteroplacenta. Carbon labelling of potential products of threonine and alanine metabolism will also be determined, particularly for other amino acids, glucose and lactate.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD029188-02
Application #
2201658
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1993-01-01
Project End
1996-12-31
Budget Start
1994-01-01
Budget End
1994-12-31
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Pediatrics
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Timmerman, M; Chung, M; Wilkening, R B et al. (1998) Relationship of fetal alanine uptake and placental alanine metabolism to maternal plasma alanine concentration. Am J Physiol 275:E942-50
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
Battaglia, F C; Wilkening, R; Meschia, G (1995) Unique organ specific characteristics of amino acid metabolism in early development. Trans Am Clin Climatol Assoc 106:141-9;discussion 149-50
Guyton, T S; De Wilt, H; Fennessey, P V et al. (1993) Alanine umbilical uptake, disposal rate, and decarboxylation rate in the fetal lamb. Am J Physiol 265:E497-503