Kinetics of ethanol inhibition of galactose elimination in perfused pig liver.
Kinetics of ethanol inhibition of galactose elimination in perfused pig liver.
复制标题
乙醇抑制灌注猪肝中半乳糖消除的动力学。
DOI：
10.3109/00365517709101836
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发表时间：
1977
影响因子：
2.1
通讯作者：
K. Tønnesen
中科院分区：
文献类型：
--
作者：
S. Keiding;S. Johansen;K. Tønnesen
用稳态输注技术，在离体灌注猪肝中研究了乙醇（5- 25 mM）对完整肝脏中半乳糖消除动力学的影响。乙醇减少半乳糖-Vmax平均为0.07 mmol/min kg肝脏在六个实验中从0.43 mmol/min kg在对照实验中获得无乙醇。Km也从0.23 mmol/l血浆水显著降低至0.03 mmol/l。乙醇使UDP-半乳糖增加10倍，同时乳酸与丙酮酸的肝流出比从10增加到约300;这表明乙醇抑制差向异构酶。在半乳糖消除速率增加的实验中，半乳糖-1-P的浓度增加远小于半乳糖的浓度，因此半乳糖的磷酸化似乎是限速的。在体外半乳糖激酶被半乳糖-1-P抑制。在本研究中，乙醇使半乳糖-1-P增加5至10倍，并且乙醇降低Vmax和Km可以解释为半乳糖-1-P的非竞争性抑制，Ki约为0.1 mmol/l。乙醇将UDP-葡萄糖降低至约40%，UTP降低至小于5%，可能是由于捕获为UDP-半乳糖。这可能会抑制正向转移酶反应，因此另一种辅助底物半乳糖-1-P升高并抑制半乳糖激酶。
The effect of ethanol (5--25 mM) on the galactose elimination kinetics in the intact liver was studied in the isolated perfused pig liver, using the steady-state infusion technique. Ethanol reduced galactose-Vmax on average to 0.07 mmol/min kg liver in six experiments from 0.43 mmol/min kg obtained in control experiments without ethanol. Also Km was significantly reduced from 0.23 mmol/l plasma water to 0.03 mmol/l. Ethanol increased UDP-galactose ten-fold simultaneous with a rise in hepatic outflow ratio of lactate to pyruvate to about 300 from 10; this indicates that ethanol inhibits epimerase. In experiments with increasing galactose elimination rates, the concentration of galactose-1-P increased much less than the concentration of galactose, and the phosphorylation of galactose therefore seems to be rate-limiting. In vitro galactokinase is inhibited by galactose-1-P. In the present study ethanol increased galactose-1-P five to ten times, and the reduction of Vmax and Km by ethanol could be explained by uncompetitive inhibition by galactose-1-P with Ki about 0.1 mmol/l. Ethanol decreased UDP-glucose to about 40% and UTP to less than 5%, probably due to trapping as UDP-galactose. This may depress the forward transferase reaction, and therefore the other co-substrate galactose-1-P rises--and inhibits galactokinase.