CONCENTRATION-DEPENDENCE OF ETHANOL-METABOLISM INVIVO IN RATS AND MAN
CONCENTRATION-DEPENDENCE OF ETHANOL-METABOLISM INVIVO IN RATS AND MAN
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DOI：
10.1111/j.1530-0277.1978.tb04748.x
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发表时间：
1978-01-01
影响因子：
3.2
通讯作者：
LIEBER, CS
中科院分区：
文献类型：
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作者：
FEINMAN, L;BARAONA, E;LIEBER, CS
乙醇到乙醛的代谢已被广泛认为几乎不依赖于浓度（即，“假线性”），除了当血液乙醇接近醇脱氢酶（ADH）的Km（0.5-1.0 m/M）时。相反，我们报告的浓度依赖性的乙醇代谢，在大鼠和人，在血液乙醇水平的几倍Km的ADH。静脉内负荷后，10只大鼠血液中38 - 17 m/甲醇水平的血液乙醇消失超过17 - 4 m/M水平（14.09 ± 1.38与8.80 ± 0.86 mmol/L血液/hr ± SEM;p< 0.001）。同样，在12名男性中，与17-4 m/M相比，30-17 m/M时血液乙醇消失得更快（5.96 ± 0.33 vs 4.96 7 plusmn; 0.28 mmole/L血液/hr ± SEM;p< 0.001）。当通过恒定静脉输注将14只禁食大鼠血液中的乙醇维持在30-60 m/莫尔或3-19 m/甲醇范围时，乙醇氧化在较高浓度下高25%（9.08 ± 0.50与7.23 ± 0.41 mmol/升血液/小时± SEM;p< 0.02）。在高乙醇浓度下乙醇氧化更快可能是由于微粒体乙醇氧化系统（MEOS）的存在，由于其Km（8.5 m/M），只有在乙醇水平超过饱和ADH所需的水平时才能完全参与。乙醇代谢的浓度依赖性使人们对通常的法医学实践的有效性产生了怀疑，即通过对随后的血液乙醇水平进行线性外推来计算先前的血液乙醇水平，这是基于代谢不受浓度影响的错误假设。
The metabolism of ethanol to acetaldehyde has been widely considered to be almost independent of concentration (i.e., “pseudolinear”) except when blood ethanol was near the Km(0.5–1.0 m/M) of alcohol dehydrogenase (ADH). On the contrary, we report the concentration dependency of ethanol metabolism, in rats and man, at blood ethanol levels several fold the Kmof ADH. After intravenous loading, blood ethanol disappearance in 10 rats at blood levels between 38 and 17 m/Methanol exceeded that between 17 and 4 m/M(14.09 ± 1.38 versus 8.80 ± 0.86 mmoles/liter blood water/hr ± SEM;p< 0.001). Similarly, in 12 men, blood ethanol disappeared faster at 30–17 m/Methanol compared to 17–4 m/M(5.96 ± 0.33 versus 4.96 7plusmn; 0.28 mmole/liter blood water/hr ± SEM;p< 0.001). When ethanol was maintained at either the 30–60 m/Mor 3–19 m/Methanol range in the blood of 14 fasted rats by constant intravenous infusion, ethanol oxidation was 25% greater at the higher concentration (9.08 ± 0.50 versus 7.23 ± 0.41 mmole/liter blood water/hr ± SEM;p< 0.02). Faster ethanol oxidation at high ethanol concentration could be due to the presence of the microsomal ethanol‐oxidizing system (MEOS), which would only be fully engaged, because of its Km(8.5 m/M), at ethanol levels exceeding those necessary to saturate ADH. The concentration dependency of ethanol metabolism casts doubt on the validity of the common medicolegal practice of calculating prior blood ethanol levels by linear extrapolation of subsequent ones, on the false assumption that metabolism is unaffected by concentration.