Metabolism of 3-methylhistidine in Man

The metabolism of L-3-methylhistidine was studied in man using intravenously administered ((14)C)3-methylhistidine. Analysis for expired (14)CO2 for periods up to 2 hr following a single intravenous injection revealed no radioactivity, indicating that this compound is not oxidized in man. Analysis of urine samples for total radioactivity showed that 75% of the administered dose was excreted in 24 hr and 95% in 48 hr. Ion-exchange chromatography of urine samples with monitoring of the column eluated by a flow liquid-scintillation technique showed the presence of only two radioactive peaks. The time taken to elute these peaks was compatible with the major excretory component (95.5%) being ((14)C)3-methylhistidine, accompanied by a small amount (4.5%) in the form of N-acetyl-((14)C)3-methylhistidine. The plasma disappearance curves of ((14)C)3-methylhistidine suggested a half-life of approximately 130 min. The inability ot oxidize 3-methylhistidine and its quantitative excretion as the original compound as well as its N-acetyl derivative is similar to its metabolic fate in the rat and therefore suggests that 3-methylhistidine excretion may provide a reliable measure of actin and myosin turnover in the whole animal or in human subjects.