The regulation of fetal protein synthesis and amino acid catabolism is central to an understanding of fetal growth, normal or aberrant. Investigations are best conducted with isotopic tracers, whereby the dilution of the tracer is used as an estimate of production, utilization and oxidation of the tracer amino acid. During the proposed project, work will continue on the model of fetal leucine kinetics, utilizing infusion of 1-13C-15N-leucine into the fetal compartment and determination of leucine carbon and nitrogen kinetics. Regulation of fetal leucine kinetics will be explored during euglycemic and hyperglycemic clamp studies, while insulin concentrations are maintained in the normal range, as well as during acute hypo- and hyperinsulinemic euglycemia. Studies will also be begun to develop and validate a three compartment fetal, uteroplacental and maternal model of leucine kinetics in the pregnant ewe. While the isotopic modeling is complex, the analytical methodology for this model is all presently being performed in our laboratory. This model will be ultimately utilized to test hypotheses regarding the manner in which alterations in maternal protein and nitrogen kinetics affect fetal growth and nitrogen balance. Finally, I will be spending periods of time in the laboratories of established experts in the fields of isotope modeling and mass spectrometric analysis. At the present time, Drs. Robert Wolfe and John Hayes have agreed to provide training and guidance in their respective laboratories for periods of one to three months. I am confident these sabbaticals will be invaluable in furthering my ability to design and apply tracer methodology to problems of mammalian fetal growth.
|Liechty, E A; Denne, S C (1998) Regulation of fetal amino acid metabolism: substrate or hormonal regulation? J Nutr 128:342S-346S|
|Ahmed, L S; Moorehead, H; Leitch, C A et al. (1998) Determination of the specific activity of sheep plasma amino acids using high-performance liquid chromatography: comparison study between liquid scintillation counter and on-line flow-through detector. J Chromatogr B Biomed Sci Appl 710:27-35|
|Liechty, E A; Boyle, D W; Moorehead, H et al. (1996) Effects of circulating IGF-I on glucose and amino acid kinetics in the ovine fetus. Am J Physiol 271:E177-85|
|Liechty, E A; Boyle, D W; Moorehead, H et al. (1993) Increased fetal glucose concentration decreases ovine fetal leucine oxidation independent of insulin. Am J Physiol 265:E617-23|
|Liechty, E A; Boyle, D W; Moorehead, H et al. (1992) Effect of hyperinsulinemia on ovine fetal leucine kinetics during prolonged maternal fasting. Am J Physiol 263:E696-702|
|Liechty, E A; Denne, S C; Lemons, J A et al. (1991) Effects of glucose infusion on leucine transamination and oxidation in the ovine fetus. Pediatr Res 30:423-9|