Kuhl D A, Mouser J F, Methvin J T, Hak E B, Hak L J, Dickerson R N
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee 38163, USA.
Nutrition. 1998 Sep;14(9):678-82. doi: 10.1016/s0899-9007(98)00067-7.
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 micrograms/48 h) and LPS-12 (557 +/- 171 micrograms/48 h) groups versus the PN (331 +/- 126 micrograms/48 h) group. NA-3-meH differed significantly between the LPS-12 (218 /+- 89 micrograms/48 h, LPS-6 (94 +/- 48 micrograms/48 h), and PN (39 +/- 12 micrograms/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.
N-甲基组氨酸（3-甲基组氨酸）在肌肉分解代谢过程中内源性释放，可作为蛋白质更新的标志物。在大鼠中，超过85%的3-甲基组氨酸以N-乙酰化衍生物的形式经尿液排出。据报道，非乙酰化3-甲基组氨酸（NA-3-甲基组氨酸）的百分比随应激变化极小。为进一步评估这些报道，我们将39只雄性Sprague-Dawley大鼠（体重157 - 213克）随机分为三组，分别仅接受肠外营养（PN），或接受PN并以6（LPS-6）或12（LPS-12）毫克·千克⁻¹·天⁻¹的剂量持续输注大肠杆菌026:B6脂多糖，共48小时。所有动物在研究前24小时及整个研究过程中均接受等热量和等氮量的PN，并自由饮水。与PN组（331 ± 126微克/48小时）相比，LPS-6组（470 ± 136微克/48小时）和LPS-12组（557 ± 171微克/48小时）的总3-甲基组氨酸排泄量显著增加（P < 0.05）。LPS-12组（218 ± 89微克/48小时）、LPS-6组（94 ± 48微克/48小时）和PN组（39 ± 12微克/48小时）之间的NA-3-甲基组氨酸差异显著（P < 0.05）。NA-3-甲基组氨酸的百分比从PN组的12.7 ± 3.9%显著增加至LPS-6组的19.8 ± 8.0%和LPS-12组的39.9 ± 12.8%（P < 0.05）。各组之间乙酰化3-甲基组氨酸未发现显著变化。这些数据表明，随着应激水平的升高，乙酰化途径可能发生饱和或受到抑制。由于在内毒素血症期间NA-3-甲基组氨酸和NA-3-甲基组氨酸百分比不成比例地增加，在大鼠中仅应使用总3-甲基组氨酸作为蛋白质更新的指标。
