Alterations in N-acetylation of 3-methylhistidine in endotoxemic parenterally fed rats

N-methylhistidine (3-meH) is endogenously released during muscle catabolism and serves as a marker of protein turnover. In rats > 85% of 3-meH is excreted in the urine as the N-acetyl derivative. It has been reported that the percent of non-acetylated 3-meH (NA-3-meH) varies minimally with stress. To further evaluate these reports, we randomized 39 male Sprague-Dawley rats (157–213 g) to receive parenteral nutrition only (PN) or PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 (LPS-6) or 12 (LPS-12) mg · kg−1 · d−1 for 48 h. All animals received isocaloric and isonitrogenous PN 24 h before and throughout the study with water ad libitum. Total 3-meH excretion was significantly increased (P < 0.05) in the LPS-6 (470 ± 136 μg/48 h) and LPS-12 (557 ± 171 μg/48 h) groups versus the PN (331 ± 126 μg/48 h) group. NA-3-meH differed significantly between the LPS-12 (218 ± 89 μg/48 h), LPS-6 (94 ± 48 μg/48 h), and PN (39 ± 12 μg/48 h) groups (P < 0.05). Percent NA-3-meH increased significantly from 12.7 ± 3.9% in the PN group to 19.8 ± 8.0 and 39.9 ± 12.8% in the LPS-6 and LPS-12 groups, respectively (P < 0.05). No significant changes in acetyl 3-meH were found between groups. These data suggest that either saturation or inhibition of acetylation pathways occurs with increasing levels of stress. Due to the disproportionate increases in NA-3-meH and percent NA-3-meH during endotoxemia, only total 3-meH should be used as an indicator of protein turnover in rats.