Rebouche C J, Engel A G
Arch Biochem Biophys. 1983 Jan;220(1):60-70. doi: 10.1016/0003-9861(83)90387-9.
This study was undertaken to quantitate the dynamic parameters of carnitine metabolism in the dog. Six mongrel dogs were given intravenous injections of L-[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 mumol/kg body wt/day. Results of this study indicate that kinetic compartmental analysis may be applicable to study of human carnitine metabolism.
本研究旨在定量犬肉碱代谢的动态参数。给6只杂种犬静脉注射L-[甲基-3H]肉碱，并在19 - 28天内跟踪血浆和尿液中肉碱的比放射性。通过动力学房室分析对数据进行分析。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]，并推导动力学参数(肉碱通量、池大小、动力学常数)。在6只犬中的4只，通过动力学房室分析获得的肌肉肉碱池大小与基于不同肌肉中肉碱浓度测量的估计值相符(±5%)。在6只犬中的3只，通过动力学房室分析得出的肉碱排泄率与实验测量值相符(±9%)，但在3只犬中，通过动力学房室分析得出的排泄率显著高于直接测量的相应速率。适当的色谱分析显示，任何一只犬的肌肉或尿液中均未发现放射性代谢物。肉碱的周转时间为(平均值±标准误)：细胞外液为0.44±0.05小时，肌肉为232±22小时，其他组织为7.9±1.1小时。估计肌肉中肉碱的通量为210 pmol/min/g组织。肉碱的全身周转时间为62.9±5.6天(平均值±标准误)。估计的肉碱生物合成范围为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类肉碱代谢的研究。
