STEADY-STATE KINETIC-PROPERTIES OF PURIFIED RAT-LIVER ALCOHOL-DEHYDROGENASE - APPLICATION TO PREDICTING ALCOHOL ELIMINATION RATES INVIVO
STEADY-STATE KINETIC-PROPERTIES OF PURIFIED RAT-LIVER ALCOHOL-DEHYDROGENASE - APPLICATION TO PREDICTING ALCOHOL ELIMINATION RATES INVIVO
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DOI：
10.1016/0003-9861(83)90213-8
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发表时间：
1983-01-01
影响因子：
3.9
通讯作者：
LI, TK
中科院分区：
文献类型：
--
作者：
CRABB, DW;BOSRON, WF;LI, TK
可以根据乙醇脱氢酶的肝脏含量（EC 1.1.1.1）、稳态速率方程以及乙醇代谢过程中肝脏中底物和产物的浓度预测进食和禁食大鼠的乙醇消除速率。比活性，动力学常数和酶的形式的多样性是相似的，在喂养和禁食大鼠，虽然肝脏中的乙醇脱氢酶含量下降福尔斯40%与禁食。酶的2种主要形式被分离，并且具有非常相似的动力学性质。大鼠乙醇脱氢酶在浓度高于10 mM时受到乙醇的底物抑制，并遵循Theorell-Chance机制。该机制的稳态速率方程预测，在低乙醇浓度下，酶的体内活性受到NADH产物抑制和在高乙醇浓度下受到NADH抑制和底物抑制的限制。当稳态速率方程和测定的底物和产品的浓度，在冷冻夹肝的喂养和禁食大鼠代谢酒精被用来计算酒精氧化速率，值同意非常好，与实际的乙醇消除率在体内测定。
The rate of ethanol elimination in fed and fasted rats can be predicted based on the liver content of alcohol dehydrogenase (EC 1.1.1.1), the steady-state rate equation, and the concentrations of substrates and products in liver during ethanol metabolism. The specific activity, kinetic constants and multiplicity of enzyme forms are similar in fed and fasted rats, although the liver content of alcohol dehydrogenase falls 40% with fasting. The 2 major forms of the enzyme were separated and had very similar kinetic properties. The rat alcohol dehydrogenase is subject to substrate inhibition by ethanol at concentrations above 10 mM and follows a Theorell-Chance mechanism. The steady-state rate equation for this mechanism predicts that the in vivo activity of the enzyme is limited by NADH product inhibition at low ethanol concentrations and by both NADH inhibition and substrate inhibition at high ethanol concentrations. When the steady-state rate equation and the measured concentrations of substrates and products in freeze-clamped liver of fed and fasted rats metabolizing alcohol are employed to calculate alcohol oxidation rates, the values agree very well with the actual rates of ethanol elimination determined in vivo.