Ruff L J, Miller L G, Brass E P
Department of Medicine, Case Western Reserve University, Cleveland, OH 44106.
Biochim Biophys Acta. 1991 Apr 9;1073(3):543-9. doi: 10.1016/0304-4165(91)90228-9.
The interaction of exogenous carnitine with whole body carnitine homeostasis was characterized in the rat. Carnitine was administered in pharmacologic doses (0-33.3 mumols/100 g body weight) by bolus, intravenous injection, and plasma, urine, liver, skeletal muscle and heart content of carnitine and acylcarnitines quantitated over a 48 h period. Pre-injection urinary carnitine excretion was circadian as excretion rates were increased 2-fold during the lights-off cycle as compared with the lights-on cycle. Following carnitine administration, there was an increase in urinary total carnitine excretion which accounted for approx. 60% of the administered carnitine at doses above 8.3 mumols/100 g body weight. Urinary acylcarnitine excretion was increased following carnitine administration in a dose-dependent fashion. During the 24 h following administration of 16.7 mumols [14C]carnitine/100 g body weight, urinary carnitine specific activity averaged only 72 +/- 4% of the injection solution specific activity. This dilution of the [14C]carnitine specific activity suggests that endogenous carnitine contributed to the increased net urinary carnitine excretion following carnitine administration. 5 min after administration of 16.7 mumol carnitine/100 g body weight approx. 80% of the injected carnitine was in the extracellular fluid compartment and 5% in the liver. Plasma, liver and soleus total carnitine contents were increased 6 h after administration of 16.7 mumols carnitine/100 g body weight. 6 h post-administration, 37% of the dose was recovered in the urine, 12% remained in the extracellular compartment, 9% was in the liver and 22% was distributed in the skeletal muscle. In liver and plasma, short chain acylcarnitine content was increased 5 min and 6 h post injection as compared with controls. Plasma, liver, skeletal muscle and heart carnitine contents were not different from control levels 48 h after carnitine administration. The results demonstrate that single, bolus administration of carnitine is effective in increasing urinary acylcarnitine elimination. While liver carnitine content is doubled for at least 6 h following carnitine administration, skeletal muscle and heart carnitine pools are only modestly perturbed following a single intravenous carnitine dose. The dilution of [14C]carnitine specific activity in the urine of treated animals suggests that tissue-blood carnitine or acylcarnitine exchange systems contribute to overall carnitine homeostasis following carnitine administration.
研究了外源性肉碱与大鼠全身肉碱稳态之间的相互作用。通过大剂量静脉推注给予大鼠药理剂量（0 - 33.3 μmol/100 g体重）的肉碱，并在48小时内对血浆、尿液、肝脏、骨骼肌和心脏中的肉碱及酰基肉碱含量进行定量分析。注射前尿肉碱排泄呈现昼夜节律，与光照期相比，熄灯期的排泄率增加了2倍。给予肉碱后，尿中总肉碱排泄量增加，在剂量高于8.3 μmol/100 g体重时，约占给予肉碱量的60%。给予肉碱后，尿中酰基肉碱排泄量呈剂量依赖性增加。在给予16.7 μmol [¹⁴C]肉碱/100 g体重后的24小时内，尿肉碱比活平均仅为注射溶液比活的72±4%。[¹⁴C]肉碱比活的这种稀释表明，内源性肉碱导致了给予肉碱后尿中净肉碱排泄量的增加。在给予16.7 μmol肉碱/100 g体重后5分钟，约80%的注射肉碱存在于细胞外液中，5%存在于肝脏中。给予16.7 μmol肉碱/100 g体重后6小时，血浆、肝脏和比目鱼肌中的总肉碱含量增加。给药后6小时，37%的剂量在尿液中回收，12%保留在细胞外液中，9%在肝脏中，22%分布在骨骼肌中。与对照组相比，注射后5分钟和6小时，肝脏和血浆中的短链酰基肉碱含量增加。给予肉碱48小时后，血浆、肝脏、骨骼肌和心脏中的肉碱含量与对照水平无差异。结果表明，单次大剂量给予肉碱可有效增加尿中酰基肉碱的排泄。给予肉碱后，肝脏肉碱含量至少在6小时内增加一倍，而单次静脉注射肉碱剂量后，骨骼肌和心脏中的肉碱池仅受到适度扰动。处理动物尿液中[¹⁴C]肉碱比活的稀释表明，组织 - 血液肉碱或酰基肉碱交换系统在给予肉碱后有助于维持整体肉碱稳态。
