Vilstrup H, Keiding S, Vendsborg P B
J Theor Biol. 1983 Apr 7;101(3):335-44. doi: 10.1016/0022-5193(83)90142-x.
Mathematical models for general substrate uptake mechanisms in the liver have been used to describe the kinetics of galactose removal. In this study sets of galactose uptake rates to galactose concentration relations obtained by perfusion of ten livers of 200 g rats were examined. The rate of galactose uptake (v) was related to the galactose concentration in the sinusoids (calculated as the logarithmic mean of in- and outlet concentration, ĉ). In all experiments a saturation pattern emerged, but the resulting 1/v versus 1/ĉ plots were all markedly convex, discarding simple Michaelis-Menten kinetics. Data were therefore examined in the light of a family of kinetic models, including the following modifications: substrate inhibition, porto-systemic shunting, and allosterism. The kinetic constants were assessed by iterative procedures, aiming at linearization of the double reciprocal plots. The two latter models were found to fit the experimental data by entering a shunting of 61% of the hepatic blood flow, or two active sites, respectively. Since this degree of shunting is improbable the results speak in favour of allosterism. The work gives an example of whole-liver kinetic considerations when simple Michaelis-Menten is insufficient.
肝脏中一般底物摄取机制的数学模型已被用于描述半乳糖清除的动力学。在本研究中，对通过灌注200克大鼠的10个肝脏获得的半乳糖摄取速率与半乳糖浓度关系的数据集进行了检查。半乳糖摄取速率（v）与肝血窦中的半乳糖浓度相关（计算为进出浓度的对数平均值，ĉ）。在所有实验中均出现了饱和模式，但所得的1/v对1/ĉ图均明显呈凸形，排除了简单的米氏动力学。因此，根据一系列动力学模型对数据进行了检查，包括以下修正：底物抑制、门体分流和变构作用。通过迭代程序评估动力学常数，旨在使双倒数图线性化。发现后两种模型分别通过引入61%的肝血流量分流或两个活性位点来拟合实验数据。由于这种分流程度不太可能，结果支持变构作用。这项工作给出了一个简单米氏动力学不足时全肝动力学考虑的例子。
