Metabolism of Administered 3-Methylhistidine

Abstract

Abstract The metabolism of l-3-methylhistidine was studied in the rat using 3-[G-3H]methylhistidine and 3-[methyl-14C] methylhistidine. The charging of skeletal muscle tRNA was examined in vitro using a pH 5 enzyme fraction, tRNA, and a mixed aminoacyl ligase preparation or an unresolved homogenate. With these systems, radioactivity from labeled leucine and histidine was transferred to tRNA in a form labile to incubation in alkaline buffers. No significant amount of radioactivity was present in the tRNA fraction when labeled 3-methylhistidine was studied under these conditions. In vivo administration of labeled 3-methyl-histidine also failed to show charging of tRNA obtained either from the pH 5 enzyme fraction of muscle or tRNA resolved from the total RNA of skeletal muscle by chromatography on Sephadex G-200. Orally or parenterally administered 3-[Me-14C]methylhistidine was quantitatively recovered in urine and feces. The urine contained unchanged 3-methylhistidine together with a metabolite identified by means of infrared and mass spectrometry and nuclear magnetic resonance and by chromatography as N-acetyl-3-methylhistidine. The proportion of the total urinary radioactivity recovered as this metabolite rose progressively from 40% in rats weighing 50 g to 90% in animals weighing over 250 g. The relative distribution of radioactivity in these two urinary compounds did not change when increasing doses of exogenous 3-methylhistidine were given to mature rats. These findings are discussed in relation to protein turnover in skeletal muscle.