Alcohol dehydrogenase activity during

J. Boehnlein, A. Sakr, J. L. Lichtin, R. L. Bronaugh, Characterization of Esterase and Alcohol Dehydrogenase Activity in Skin. Metabolism of Retinyl Palmitate to Retinol (Vitamin A) During Percutaneous Absorption , Pharm. Res. 1994, 11, 1155-1159. 

Boehnlein, J., Sakr, S., Lichtin, J.L., and Bronaugh, R.L., 1994, Characterization of esterase and alcohol dehydrogenase activity in skin. Metabolism of retinyl palmitate to retinol (vitamin A) in skin during percutaneous absorption, Pharm. Res., 11 1155-1159. 

Alcohol dehydrogenase activity (ADH) and peroxidase activity (POD) measurements performed during the process of LADH spin labeling, confirm the previously found evidence that both types of activities utilize the same enzyme active site (1). Actually, as shown in Pig. 1, the two catalytic activities decay at the same rate, suggesting a very similar effect of the spin label sensitive Cys-46 residue alkylation on both of them. 

Figure 1.9 Examples of functionally important intrinsic metal atoms in proteins, (a) The di-iron center of the enzyme ribonucleotide reductase. Two iron atoms form a redox center that produces a free radical in a nearby tyrosine side chain. The iron atoms are bridged by a glutamic acid residue and a negatively charged oxygen atom called a p-oxo bridge. The coordination of the iron atoms is completed by histidine, aspartic acid, and glutamic acid side chains as well as water molecules, (b) The catalytically active zinc atom in the enzyme alcohol dehydrogenase. The zinc atom is coordinated to the protein by one histidine and two cysteine side chains. During catalysis zinc binds an alcohol molecule in a suitable position for hydride transfer to the coenzyme moiety, a nicotinamide, [(a) Adapted from P. Nordlund et al., Nature 345 593-598, 1990.)...

Enzyme Cofactors- In many enzymatic reactions, and in particular biological reactions, a second substrate (i.e., species) must be introduced to activate the enzyme. This substrate, which is referred to as a cofactor or coenzyme even though it is not an enzyme as such, attaches to the enzyme and is most often either reduced or oxidized during the course of die reaction. The enzyme-cofactor complex is referred to as a holoenzyme. The inactive form of the enzyme-cofactor complex for a specific reaction and reaction direction is called an apoenzyme. An example of the type of system in which a cofactor is used is the formation of ethanol from acetaldehyde in the presence of the enzyme alcohol dehydrogenase (ADH) and the cofactor nicotinamide adenine dinuoleotide (NAD) ... 

Isopropanol has a short half-life ti ) of 1 to 6 hours, as it is rapidly metabolized by alcohol dehydrogenase to acetone, which is eliminated much more slowly (t]/2,17 to 27 hours), primarily in alveolar air and urine.Therefore concentrations of acetone in serum often exceed those of isopropanol during the elimination phase following isopropanol mgestion (Figure 34-4). Acetone has CNS depressant activity similar to that of ethanol, and because of its longer half-life, it prolongs the apparent CNS effects of isopropanol. 

The belief that alcoholics are more susceptible to the toxicity of 2,4-DNP during occupational exposure (Perkins 1919) may indicate an interaction with ethanol (and possibly other alcohols) or it may simply be a function of the compromised physiological state of alcoholics. 2,4-DNP appears to markedly increase the rate of ethanol metabolism in rat liver slices by 100-160% (Videla and Israel 1970) and in rats in vivo by 20-30% (Israel et al. 1970). Because 2,4-DNP uncouples mitochondrial electron transport from oxidative phosphorylation, the oxidation of NADH to NAD is accelerated in the mitochondria. Reoxidation of NADH rather than the activity of alcohol dehydrogenase is the rate-limiting step in the metabolism of ethanol, and, therefore, the metabolic effect of 2,4-DNP enhances the clearance of ethanol (Eriksson et al. 1974). Because 2,4-DNP is known to augment the rate of respiration and perspiration, 2.7-8.2% of the initial dose of ethanol was also eliminated by expiration and cutaneous evaporation in the rat (Israel et al. 1970). 

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