ALTERATIONS IN N-ACETYLATION OF 3-METHYLHISTIDINE IN ENDOTOXEMIC PARENTERALLY FED RATS

N-methylhistidine (3-meH) is endogenously released during muscle catab olism and serves as a marker of protein turnover. In rats > 85% of 3-m eH is excreted in the urine as the N-acetyl derivative. It has been re ported that the percent of non-acetylated 3-meH (NA-3-meH) varies mini mally 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 coil 026:B6 li popolysaccharide at 6 (LPS-6) or 12 (LPS-12) mg . kg(-1) . d(-1) for 4 8 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 mu g /48 h) and LPS-12 (557 +/- 171 mu g/48 h) groups versus the PN (331 +/ - 126 mu g/48 h) group. NA-3-meH differed significantly between the LP S-12 (218 +/- 89 mu g/48 h), LPS-6 (94 +/- 48 mu g/48 h), and PN (39 /- 12 mu g/48 h) groups (P < 0.05). Percent NA-3-meH increased signifi cantly 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 sig nificant 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 i ncreases in NA-3-meH and percent NA-3-meH during endotoxemia, only tot al 3-meH should be used as an indicator of protein turnover in rats. N utrition 1998;14:678-682. (C) Elsevier Science Inc. 1998.