A KINETIC DESCRIPTION OF THE FATE OF CHEMICALS IN BIOSYSTEMS
A KINETIC DESCRIPTION OF THE FATE OF CHEMICALS IN BIOSYSTEMS
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DOI：
10.1016/0048-9697(91)90190-p
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发表时间：
1991-12-01
影响因子：
9.8
通讯作者：
SEYDEL, JK
中科院分区：
文献类型：
--
作者：
BALAZ, S;WIESE, M;SEYDEL, JK
利用质量作用定律，推导了低分子化合物在生物系统中的去向的简单动力学描述。针对酶反应的两种边界条件，即一级动力学和零级动力学，考虑了酶反应的Michaelis-Menten动力学。模型包括吸收、膜积累、非共价蛋白结合、生物转化和排泄，只有后两个步骤被认为是与时间相关的，以小时和天为相关的时间尺度。这种时间层次结构允许对结果表达式进行简化。根据摄取实验的结果，与以前的方法相反，有机分子进入细胞的运输不被认为是速率限制步骤。决定化合物性质的是疏水性和生物转化和排泄的内禀速率参数。该模型被用于解释观察到的生物转化率参数与疏水性的关系。所得方程与文献数据吻合较好。
A simple kinetic description of the fate of low-molecular-weight compounds in biosystems was derived using the mass action law. Michaelis-Menten kinetics of enzymatic reactions was considered with respect to its two boundary cases, namely first- and zero-order kinetics. Absorption, membrane accumulation, non-covalent protein binding, biotransformation, and excretion have been included in the model, with only the last two steps being considered as time-dependent on the pertinent time scale of hours and days. This time hierarchy allowed for simplification of the resulting expression. In accordance with the results of uptake experiments and contrary to previous approaches, transport of organic molecules into the cell was not considered as the rate-limiting step. The decisive compound properties were found to be hydrophobicity and the intrinsic rate parameters of biotransformation and excretion. The model was applied to the elucidation of the dependence of the observed biotransformation rate parameters on hydrophobicity. The resulting equations are consistent with literature data.