Cerebral leucine uptake and protein synthesis in the near-term ovine fetus: relation to fetal behavioral state

Canadian Institute of Health Research Group in Fetal and Neonatal Health and Development, Departments of Obstetrics and Gynaecology and Physiology, Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada N6A 4V2; and Department of Pediatrics, Division of Neonatology, University of Utah, Salt Lake City, Utah 84132 Behavioral/sleep state activity may impact on synthetic processes within the brain, thus accounting for the developmental change in such activity and suggesting a role in the brain's growth and development. We have therefore determined the cerebral uptake of leucine and [ 14 C]leucine during continuous tracer infusion as measures of leucine metabolism in relation to behavioral state activity, as well as the regional flux of leucine into brain tissue in the ovine fetus near term. The cerebral fractional protein synthetic rate and the absolute protein synthetic rate averaged ~20%/day and ~1 g/day, respectively, as measured for the whole brain, which is considerably higher than anticipated protein accretion and indicates a high rate of protein turnover with protein synthesis closely linked to protein degradation. Measures of protein synthesis were significantly higher in the pituitary gland, which may be attributed to the active synthesis and export of peptide hormones from this region. Cerebral leucine and [ 14 C]leucine uptakes averaged ~630 and ~1,000 nmol · 100 g 1 · min 1 , with the latter higher than leucine unidirectional flux and thus supporting a degree of leucine oxidation by the brain. Cerebral leucine metabolism as studied was affected by behavioral state activity, with uptake measurements for both leucine and [ 14 C]leucine significantly increased during the high-voltage electrocortical/non-rapid eye movement state by 1.7-fold and 2.8-fold, respectively, indicating that protein synthesis and degradation must also be increased at this time, and supporting a role for behavioral state activity in the brain's growth and development. brain development; leucine metabolism