INVIVO EFFECT OF L-LEUCINE ADMINISTRATION ON PROTEIN-SYNTHESIS IN MICE

To clarify the in vivo effect of leucine on protein synthesis within a short period, the fractional formation rate of peptidyl puromycin (FFR) was measured in the liver and skeletal muscle of mice. FFR was calculated as the ratio of specific activity of peptide-bound puromycin at 10 minutes after injection of [H-3]puromycin to the area under the specific activity-time curve of free puromycin. The value of FFR corresponds to the amount of tracer puromycin bound in unit time, expressed as a fraction of the total amount of puromycin potentially bound to the aminoacyl-site on the functional ribosome pool. In 12-hour fasted, streptozotocin-induced diabetic mice, L-leucine injection (360-mu-mol/100 g body weight) increased the FFR in the liver but not in muscle, while the injection of insulin (0.5 unit/100 g body weight) raised the rate in muscle but not in the liver. The leucine-induced rise of FFR in the liver was blocked by a cyclooxygenase inhibitor, indomethacin, although this inhibitor did not block the insulin-stimulated rise of FFR in muscle. No significant increase in FFR was detected in the liver or muscle of non-diabetic mice by leucine injection. L-leucine injection caused a slight decrease of ribosome aggregation in the liver but not in muscle, while insulin injection led to ribosome aggregation in muscle but not in the liver of diabetic mice. The enhancement of FFR in the liver of diabetic animals by leucine injection suggests that leucine may stimulate protein synthesis in part by increasing the rate of elongation.