Epoxide inhibition of alcohol dehydrogenases. Identification of modified cysteines in yeast alcohol dehydrogenase and demonstration of reversible and irreversible inhibition of liver alcohol dehydrogenase by styrene oxide

Biochemistry ◽  
1977 ◽  
Vol 16 (25) ◽  
pp. 5521-5527 ◽  
Author(s):  
Judith P. Klinman ◽  
Katherine M. Welsh ◽  
Ruth Ogue-Angeletti
Keyword(s):  
Alcohol Dehydrogenase ◽  
Styrene Oxide ◽  
Alcohol Dehydrogenases ◽  
Irreversible Inhibition ◽  
Yeast Alcohol Dehydrogenase ◽  
Liver Alcohol Dehydrogenase

scholarly journals Inhibition by ethanol, acetaldehyde and trifluoroethanol of reactions catalysed by yeast and horse liver alcohol dehydrogenases

1978 ◽  
Vol 171 (3) ◽  
pp. 613-627 ◽  
Author(s):  
C J Dickenson ◽  
F M Dickinson
Keyword(s):  
Alcohol Dehydrogenase ◽  
Dissociation Constant ◽  
Maximum Rate ◽  
Alternative Pathway ◽  
Product Inhibition ◽  
Experimental Conditions ◽  
Alcohol Dehydrogenases ◽  
Yeast Alcohol Dehydrogenase ◽  
Liver Alcohol Dehydrogenase ◽  
Horse Liver

1. Produced inhibition by ethanol of the acetaldehyde-NADH reaction, catalysed by the alcohol dehydrogenases from yeast and horse liver, was studied at 25 degrees C and pH 6-9. 2. The results with yeast alcohol dehydrogenase are generally consistent with the preferred-pathway mechanism proposed previously [Dickenson & Dickinson (1975) Biochem. J. 147, 303-311]. The observed hyperbolic inhibition by ethanol of the maximum rate of acetaldehyde reduction confirms the existence of the alternative pathway involving an enzyme-ethanol complex. 3. The maximum rate of acetaldehyde reduction with horse liver alcohol dehydrogenase is also subject to hyperbolic inhibition by ethanol. 4. The measured inhibition constants for ethanol provide some of the information required in the determination of the dissociation constant for ethanol from the active ternary complex. 5. Product inhibition by acetaldehyde of the ethanol-NAD+ reaction with yeast alcohol dehydrogenase was examined briefly. The results are consistent with the proposed mechanism. However, the nature of the inhibition of the maximum rate cannot be determined within the accessible range of experimental conditions. 6. Inhibition of yeast alcohol dehydrogenase by trifluoroethanol was studied at 25 degrees C and pH 6-10. The inhibition was competitive with respect to ethanol in the ethanol-NAD+ reaction. Estimates were made of the dissociation constant for trifluoroethanol from the enzyme-NAD+-trifluoroethanol complex in the range pH6-10.

scholarly journals The physiological role of liver alcohol dehydrogenase

1970 ◽  
Vol 118 (4) ◽  
pp. 635-644 ◽  
Author(s):  
H. A. Krebs ◽  
J. R. Perkins
Keyword(s):  
Alcohol Dehydrogenase ◽  
Portal Vein ◽  
Alimentary Canal ◽  
Alcohol Concentration ◽  
The Body ◽  
Portal Blood ◽  
Dietary Habit ◽  
Germ Free ◽  
Yeast Alcohol Dehydrogenase ◽  
Liver Alcohol Dehydrogenase

1. Yeast alcohol dehydrogenase was used to determine ethanol in the portal and hepatic veins and in the contents of the alimentary canal of rats given a diet free from ethanol. Measurable amounts of a substance behaving like ethanol were found. Its rate of interaction with yeast alcohol dehydrogenase and its volatility indicate that the substance measured was in fact ethanol. 2. The mean alcohol concentration in the portal blood of normal rats was 0.045mm. In the hepatic vein, inferior vena cava and aorta it was about 15 times lower. 3. The contents of all sections of the alimentary canal contained measurable amounts of ethanol. The highest values (average 3.7mm) were found in the stomach. 4. Infusion of pyrazole (an inhibitor of alcohol dehydrogenase) raised the alcohol concentration in the portal vein 10-fold and almost removed the difference between portal and hepatic venous blood. 5. Addition of antibiotics to the food diminished the ethanol concentration of the portal blood to less than one-quarter and that of the stomach contents to less than one-fortieth. 6. The concentration of alcohol in the alimentary canal and in the portal blood of germ-free rats was much decreased, to less than one-tenth in the alimentary canal and to one-third in the portal blood, but detectable quantities remained. These are likely to arise from acetaldehyde formed by the normal pathways of degradation of threonine, deoxyribose phosphate and β-alanine. 7. The results indicate that significant amounts of alcohol are normally formed in the gastro-intestinal tract. The alcohol is absorbed into the circulation and almost quantitatively removed by the liver. Thus the function, or a major function, of liver alcohol dehydrogenase is the detoxication of ethanol normally present. 8. The alcohol concentration in the stomach of alloxan-diabetic rats was increased about 8-fold. 9. The activity of liver alcohol dehydrogenase is generally lower in carnivores than in herbivores and omnivores, but there is no strict parallelism between the capacity of liver alcohol dehydrogenase and dietary habit. 10. The activity of alcohol dehydrogenase of gastric mucosa was much decreased in two out of the three germ-free rats tested. This is taken to indicate that the enzyme, like gastric urease, may be of microbial origin. 11. When the body was flooded with ethanol by the addition of 10% ethanol to the drinking water the alcohol concentration in the portal vein rose to 15mm and only a few percent of the incoming ethanol was cleared by the liver.

Kinetics of Irreversible Inhibition of Yeast Alcohol Dehydrogenase during Modification by o-Phthaldehyde

1994 ◽  
Vol 48 (3) ◽  
pp. 183-190 ◽  
Author(s):  
Wei-Ping Le ◽  
Si-Xu Yan ◽  
Ming-Qian Huang ◽  
Ying-Xia Zhang ◽  
Hai-Meng Zhou
Keyword(s):  
Alcohol Dehydrogenase ◽  
Irreversible Inhibition ◽  
Yeast Alcohol Dehydrogenase ◽  
Kinetics Of

scholarly journals Reduction of acetaldehyde to ethanol by some micro-organisms and its stereospecificity

1988 ◽  
Vol 250 (3) ◽  
pp. 929-932 ◽  
Author(s):  
E Maconi ◽  
A Griffini ◽  
V Cavazzoni ◽  
F Aragozzini
Keyword(s):  
Alcohol Dehydrogenase ◽  
Alcohol Dehydrogenases ◽  
Yeast Alcohol Dehydrogenase ◽  
Micro Organisms

The stereochemical course of the reduction of acetaldehyde to ethanol was investigated by evaluating, with the enzymic system yeast alcohol dehydrogenase/diaphorase and g.c.-m.s., the configuration of [1-2H]ethanol obtained from [1-2H]acetaldehyde with different micro-organisms. Although only S-[1-2H]ethanol was formed, all the micro-organisms showed evidence of the existence of alcohol dehydrogenases with opposite stereospecificity.

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