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

Abstract

1. The validity of the urinary excretion of Nτ-methyl histidine (Nτ-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 Nτ-[14CH3]methylhistidine.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 Nτ-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 Nτ-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 Nτ-MH released by breakdown of muscle protein. Hence, only a proportion of the Nτ-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 Nτ-MH in muscle consisted of free Nτ-MH and a dipeptide containing Nτ-MH, the latter comprising on average approximately 82% of the total non-protein-bound Nτ-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 Nτ-MH and was not a terminal product of protein breakdown.7. The results show that urinary excretion of Nτ-MH is not a reliable index of muscle protein breakdown in sheep.