COMPARISON OF TWO METHODS FOR STUDYING PROTEIN METABOLISM IN HEALTHY ADULTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In vivo whole body protein turnover and oxidation are usually measured by the plasma enrichment of an amino acid labeled in the carboxyl position with 13C (e.g., 1-13C-leucine) and breath 13CO2 following intravenous infusion of the labeled amino acid. While sufficiently non-invasive in adults and older children, this method is often considered too invasive for use in small preterm infants. Hence, its use to study protein metabolism of this population has been limited. In theory, it should be possible to administer the labeled amino acid by mouth and measure its enrichment in urine and the enrichment of 13CO2 in breath. A few studies, some in infants and some in adults, suggest that the two approaches result in similar enrichment in plasma and urine but all aspects of the two techniques have never been compared in the same individuals. To accomplish this, healthy men and non-pregnant women (age, 18-40 years) will be studied on two occasions. On the first, they will receive a primed constant intravenous infusion of 1-13C-leucine or a primed intermittent ingestion of 13C-leucine. A week later, they will receive the same dose of 1-13C-leucine by the alternative route. Plasma and urinary enrichments of leucine and breath 13CO2 enrichment will be determined on both occasions. This will permit comparison of the conventional method (constant intravenous administration and plasma sampling) with the less invasive method (primed intermittent enteral administration and urine sampling) as well as any combination of the two (intravenous administration and urine sampling). Flux, protein synthesis and protein breakdown calculated with data obtained by both approaches also will be compared. The data to be obtained will provide the first thorough evaluation of these two methods for studying whole body protein metabolism and whether the invasive conventional method can be replaced by the less invasive method.