Alcohol dehydrogenase reaction

Welsh, K.M., Creighton, D.J. and Khnman, J.P. (1980). Transition-state structure in the yeast alcohol dehydrogenase reaction the magnitude of solvent and alpha-secondary hydrogen isotope effects. Biochemistry 19, 2005-2016... 

Klinman, J.P. (1976). Isotope effects and structure-reactivity correlations in the yeast alcohol dehydrogenase reaction. A study of the enzyme-catalyzed oxidation of aromatic alcohols. Biochemistry 15, 2018-2026... 

Chin, J.K. and Klinman, J.P. (2000). Probes of a role for remote binding interactions on hydrogen tunneling in the horse liver alcohol dehydrogenase reaction. Biochemistry 39, 1278-1284... 

Klinman, J.P. (1981). Probes of mechanism and transition-state structure in the alcohol dehydrogenase reaction. CRC Crit. Rev. Biochem. 10, 39-78... 

This reaction should not be confused with the monooxygenation of ethanol by CYP that occurs in the microsomes. The alcohol dehydrogenase reaction is reversible, with the carbonyl compounds being reduced to alcohols. 

Answer The mechanism is the same as that of the alcohol dehydrogenase reaction (Fig. 14-13, p. 547). 

These properties for the alcohol dehydrogenase reaction can be plotted as functions of temperature and pH. 

B. V. PiAPP, J. P. Klinman, Unmasking of hydrogen tunneling in the horse liver alcohol dehydrogenase reaction by site-directed mutagenesis. Biochemistry 32, 5503-5507 (1993). 

Once intrinsic isotope effects are determined, one is in a position to deduce transition state stmcture, just as the physical organic chemist does for nonen-zymic reactions. Unfortunately, in many cases workers have assumed, rather than proved, that commitments are zero and intrinsic isotope effects were being looked at. Transition state structures have been investigated in the formate and liver alcohol dehydrogenase reactions as the redox potential of the nucleotide substrate was changed (103, 118). Primary deuterium and C, secondary deuterium, and for formate dehydrogenase 0 isotope effects were determined. In both cases the transition states appeared to be late with NAD and to become earlier as the redox potential of the nucleotide became more positive. So far the conclusions from such studies have been qualitative in nature, and there is room for much more work on these systems. 

H]serine formed was degraded into ethanol in such a way that C-3 of serine becomes C-1 of ethanol, and the alcohol dehydrogenase reaction was then used to establish the enantiomeric purity and the absolute configuration of the labelled centre. The sample was in fact 72% (S)-[l- H]ethanol and therefore the tritiated serine contained 72% of the label in the (35) and the remainder in the (3R) isomer (see Fig. 17). 

The alcohol dehydrogenase reaction occurs in the opposite direction when ethanol is consumed. Alcohol dehydrogenase is found in liver and intestinal tissue. The acetaldehyde produced by liver alcohol dehydrogenase may contribute to short- and long-term alcohol toxicity. Conversely, different levels of intestinal alcohol dehydrogenase may help explain why some individuals show more profound effects after only one or two drinks than others. Apparently, some of the ethanol consumed is metabolized by intestinal alcohol dehydrogenase before it reaches the nervous system. 

To detect the presence of abortive ternary complexes, the kinetidst may raise the concentration of dissimilar substrate-product pairs (such as glucose-ADP and ATP-glucose-6-P in the hexokinase reaction, or acetaldehyde-NAD and ethanol-NADH in alcohol dehydrogenase reaction). This wiU lead to the inhibition of all exchanges irrespective of the kinetic mechanism, and provide useful information about the abortive complex formation (Wong Hanes, 1964 Wedler Boyer, 1972 Punch Allison, 1980, 2000). Nevertheless, product inhibition is stiU unrivaled as the means for detecting abortive complex formation. 

The equilibrium of the alcohol dehydrogenase reaction is far in favor of ethanol however, ethanol conversion can be completed by continuous oxidation of acetaldehyde dehydrogenase reaction. 

Groups we discuss the stereochemical aspect of alcohol dehydrogenase reactions. 

The alcohol dehydrogenase reaction produces a high ratio of NADH/ NAP" In the cytosol... 

Damgaard SE (1981) Primary deuterium and tritium isotope effects upon V/K in the liver alcohol dehydrogenase reaction with ethanol. Biochemistry 20 5662-5669... 

San Pietro A, Kaplan NO, Colowick SP (1955) Pyridine nucleotide transhydrogenase VI. Mechanism and stereospecificity of the reaction in pseudomonas fluorescens. J Biol Chem 212 941-952 Schmidt J, Chen J, De Traglia M, Minkel D McFarland JT (1979) Solvent deuterium isotope effect on the liver alcohol dehydrogenase reaction. J Am Chem Soc 101 3634-3640 Schowen RL (1978) Catalytic power and transition-state stabilization. In Candour RD, Schowen RL (ed) Transition states of biological... 

AFo is the standard free energy of the reaction, and must not be confused with the constant F, usually written in bold type to minimize confusion. In the example of the alcohol dehydrogenase reaction at pH 7.0, AFo may be evaluated from oxidation-reduction potentials without first calculating the equilibrium constant. 

Enzyme Studies - Log P, along with the Hammett a constant, has found use in the correlation of enzymic reactions. The study of Blomquist on the electronic effects of substituents in alcohol dehydrogenase reactions illustrates the point. Blomquist noted that both electronic and hydrophobic effects appear to be involved in the enzymic reduction of benzaldehydes. 

---