FETAL BRANCHED-CHAIN AMINO ACID AND KETO-ACID METABOLISM

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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.