The urinary excretion of N tau-methyl histidine in sheep: an invalid index of muscle protein breakdown.

1. The validity of the urinary excretion of N tau-methyl histidine (N tau-MH) in sheep as a measure of the breakdown of muscle protein in vivo was assessed from the urinary recovery of radioactivity following the intravenous administration of N tau-[14CH3]methyl histidine. 2. Recoveries of radioactivity in urine from animals of 4 weeks to 7 years of age were incomplete in 7 d but progressively increased with the age of the animal, becoming almost quantitative (90%) in older animals after recovery for 3 weeks. 3. The incomplete urinary recoveries were not due to partial excretion of N tau-MH in faeces or its oxidation and elimination in expired gases but were related to the presence in muscle of a pool of non-protein-bound N tau-MH which was several times larger than the expected daily urinary excretion. 4. This pool in newly accreted muscle tissue was maintained by retention of some of the N tau-MH released by breakdown of muscle protein. Hence, only a proportion of the N tau-MH released from protein breakdown was available for excretion. This proportion increased with the age of the animal and was probably the main determinant of the improved recoveries of radioactivity obtained in urine from older animals. 5. The non-protein-bound N tau-MH in muscle consisted of free N tau-MH and a dipeptide containing N tau-MH, the latter comprising on average approximately 82% of the total non-protein-bound N tau-MH in muscle. This proportion did not change appreciably with the age of the animal. 6. The dipeptide appeared to be synthesized in muscle from free N tau-MH and was not a terminal product of protein breakdown. 7. The results show that urinary excretion of N tau-MH is not a reliable index of muscle protein breakdown in sheep.