On the uptake of materials by the intact liver. The transport and net removal of galactose.
On the uptake of materials by the intact liver. The transport and net removal of galactose.
复制标题
关于完整肝脏对物质的吸收。
DOI：
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发表时间：
1973
影响因子：
15.9
通讯作者：
B. Nadeau
中科院分区：
文献类型：
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作者：
C. Goresky;G. Bach;B. Nadeau
D-半乳糖是一种在肝细胞内迅速磷酸化的单糖，它被不可逆转地从门静脉循环中移除。我们用多指示剂稀释技术研究了肝细胞进入过程和代谢隔离过程之间的动力学关系。将标记的红细胞(血管指示剂)、标记的蔗糖(细胞外参照)和标记的半乳糖快速注入门静脉，并从快速采样的肝静脉血中获得正常化的流出时间模式。标记的红细胞曲线上升到最高峰和最早峰，并迅速衰减；标记蔗糖的红细胞曲线上升到较晚的峰和较低的峰。其外推回收率相当于标记红细胞的回收率。在血液中半乳糖浓度较低时，标记的半乳糖出现在标记蔗糖的流出端，但数量大大减少，并显示出较长的拖尾。它的流出回收率大大降低。当血液中半乳糖浓度较高时，图谱的初始部分向标记蔗糖的方向增加，尾部变得更大，流出恢复几乎完全完成。我们已经对标记的半乳糖的吸收进行了建模，并发现了预测的流出模式的两个部分，与我们的实验观察相对应；吞吐量物质，它扫过细胞外空间的细胞表面；以及返回的物质，它已经进入细胞，但逃脱了隔离过程。使用该模型对数据进行分析，可以估计跨膜通量和隔离速率。细胞进入过程的能力是磷酸化能力的40倍，而封闭的K(M)值小于15 mg/100ml，而进入的K(M)值约为500 mg/100ml。这两个过程都是相对立体特异的；L立体异构体的进入非常缓慢，它没有经历显著的代谢隔离。隔离过程产生小叶细胞内浓度梯度；而该梯度又在隔离过程的真实K(M)值的估计中产生一些不确定性。
D-galactose, a monosaccharide rapidly phosphorylated within liver cells, is irreversibly removed from the portal circulation. We have studied the kinetic relations between the hepatic cell entry process and the metabolic sequestration process, by means of the multiple indicator dilution technique. Labeled red blood cells (a vascular indicator), labeled sucrose (an extracellular reference), and labeled galactose were rapidly injected into the portal vein, and from rapidly sampled hepatic venous blood, normalized outflow-time patterns were secured. The labeled red cell curve rises to the highest and earliest peak, and decays rapidly; and that for labeled sucrose rises to a later and lower peak. Its extrapolated recovery is equivalent to that of the labeled red cells. At low blood galactose concentrations, the labeled galactose appears at the outflow with labeled sucrose, but is much reduced in magnitude, and exhibits a long tailing. Its outflow recovery is much reduced. At high blood galactose concentrations, the initial part of the profile increases towards that for labeled sucrose, the tailing becomes much larger in magnitude, and the outflow recovery becomes virtually complete. We have modeled the uptake of labeled galactose, and find two parts to the predicted outflow pattern, corresponding to our experimental observations; throughput material, which sweeps past the cell surface in the extracellular space; and returning material, which has entered the cells but escaped the sequestration process. Analysis of the data by use of this model provides estimates of both transmembrane fluxes and rates of sequestration. The capacity of the process subserving cell entry is found to be 40 times that for phosphorylation; and, whereas the K(m) value for sequestration is less than 15 mg/100 ml, that for entry is approximately 500 mg/100 ml. Both processes are relatively stereospecific; the entry of the L-stereoisomer is very slow and it undergoes no significant amount of metabolic sequestration. The sequestration process produces a lobular intracellular concentration gradient; and this gradient, in turn, produces some uncertainty in the estimate of the true K(m) value for the sequestration process.