Michaelis-Menten kinetics of galactose elimination by the isolated perfused pig liver.

Michaelis-Menten kinetics of galactose elimination by the isolated perfused pig liver.
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离体灌注猪肝消除半乳糖的 Michaelis-Menten 动力学。

DOI:
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发表时间:
1976
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通讯作者:
N. Tygstrup
N. Tygstrup
中科院分区:
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文献类型:
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作者:
S. Keiding;S. Johansen;K. Winkler;K. Tønnesen;N. Tygstrup

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用数学动力学模型分析了猪肝脏半乳糖清除率与血药浓度的关系。它假定在稳态条件下,通过遵循Michaelis-Menten(即饱和)动力学的不可逆过程,从流经正弦的血液中去除底物。实验包括持续不断地注入半乳糖的连续阶段。该模型将数据拟合到实验不确定度范围内。在9个实验中,估计的最大速率(Vmax)范围为0.34至0.57 mmol·min(-1)·kg(-1)肝脏,Michaelis常数Km为0.12至0.30 mmol·L~(-1)血浆水。肝细胞水中半乳糖浓度与血浆水中半乳糖浓度之比与1.0相比无显著差异,说明膜转运对半乳糖的清除不是速率限制。在增加肝细胞水中半乳糖浓度和接近饱和消除速率的实验中,半乳糖1-磷酸、UDP半乳糖和UDP葡萄糖的浓度基本保持不变。这表明半乳糖的磷酸化为1-磷酸半乳糖是决定速率的过程。
The relation between galactose elimination rates and blood concentrations in the isolated perfused pig liver was analyzed by a mathematical kinetic model. It assumes that the substrate, under steady-state conditions, is removed from the blood that flows through the sinusoids by an irreversible process which follows Michaelis-Menten (i.e., saturation) kinetics. The experiments consisted of successive periods with constant infusions of galactose. The model fitted the data to within the experimental uncertainty. The estimated maximal rate (Vmax) ranged from 0.34 to 0.57 mmol-min(-1)-kg(-1) liver, and the Michaelis constant, Km, ranged from 0.12 to 0.30 mmol-liter(-1) plasma water in nine experiments. The ratio between the galactose concentration in hepatocyte water and plasma water was not significantly different from 1.0, indicating that membrane transport is not rate limiting for the elimination of galactose. In experiments with increasing concentrations of galactose in hepatocyte water and approximately saturated elimination rates, the concentrations of galactose 1-phosphate, UDPgalactose, and UDPglucose remained essentially constant. This indicates that the phosphorylation of galactose to galactose 1-phosphate is the rate-determining process.