Kinetic compartmental analysis of carnitine metabolism in the dog.
Kinetic compartmental analysis of carnitine metabolism in the dog.
复制标题
狗肉碱代谢的动力学区室分析。
DOI：
10.1016/0003-9861(83)90387-9
复制
发表时间：
1983
影响因子：
3.9
通讯作者：
Engel,AG
中科院分区：
文献类型：
--
作者：
Rebouche,CJ;Engel,AG
本研究旨在定量测定犬体内肉毒碱代谢的动力学参数。6只杂种犬静脉注射1-[甲基-3H]肉毒碱，连续19-28天，观察血浆和尿液中肉毒碱的放射性。用动力学房室模型分析数据。采用三室、开放系统模型[（a）细胞外液，（B）心脏和骨骼肌，（c）其他组织，特别是肝脏和肾脏]并推导出动力学参数（肉毒碱通量、池大小、动力学常数）。在6只犬中的4只中，通过动力学房室分析获得的肌肉肉毒碱池的大小与基于不同肌肉中肉毒碱浓度测量的估计值一致（±5%）。在6只犬中的3只犬中，来自动力学房室分析的肉毒碱排泄率与实验测量值一致（±9%），但在3只犬中，动力学房室分析的排泄率显著高于直接测量的相应排泄率。适当的色谱分析显示任何犬的肌肉或尿液中均无放射性代谢产物。肉毒碱的周转时间（平均值± SEM）：细胞外液为0.44 ± 0.05 h，肌肉为232 ± 22 h，其他组织为7.9 ± 1.1 h。肌肉中肉毒碱的估计通量为210 pmol/min/g组织。肉毒碱的全身周转时间为62.9 ± 5.6天（平均值± SEM）。估计的肉毒碱生物合成范围为2.9至28 μmol/kg体重/天。本研究结果表明，动力学房室分析可能适用于人体肉毒碱代谢的研究。
This study was undertaken to quantitate the dynamic parameters of carnitine metabolism in the dog. Six mongrel dogs were given intravenous injections ofl-[methyl-3H]carnitine and the specific radioactivity of carnitine was followed in plasma and urine for 19–28 days. The data were analyzed by kinetic compartmental analysis. A three-compartment, open-system model [(a) extracellular fluid, (b) cardiac and skeletal muscle, (c) other tissues, particularly liver and kidney] was adopted and kinetic parameters (carnitine flux, pool sizes, kinetic constants) were derived. In four of six dogs the size of the muscle carnitine pool obtained by kinetic compartmental analysis agreed (±5%) with estimates based on measurement of carnitine concentrations in different muscles. In three of six dogs carnitine excretion rates derived from kinetic compartmental analysis agreed (±9%) with experimentally measured values, but in three dogs the rates by kinetic compartmental analysis were significantly higher than the corresponding rates measured directly. Appropriate chromatographic analyses revealed no radioactive metabolites in muscle or urine of any of the dogs. Turnover times for carnitine were (mean ± SEM): 0.44 ± 0.05 h for extracellular fluid, 232 ± 22 h for muscle, and 7.9 ± 1.1 h for other tissues. The estimated flux of carnitine in muscle was 210 pmol/min/g of tissue. Whole-body turnover time for carnitine was 62.9 ± 5.6 days (mean ± SEM). Estimated carnitine biosynthesis ranged from 2.9 to 28 μmol/kg body wt/day. Results of this study indicate that kinetic compartmental analysis may be applicable to study of human carnitine metabolism.