Alcohol dehydrogenases ,

Alcohol dehydrogenases are a class of zinc enzymes which catalyse the oxidation of primary and secondary alcohols to the corresponding aldehyde or ketone by the transfer of a hydride anion to NAD+ with release of a proton. 

As a class of enzymes, the alcohol dehydrogenases catalyze the conversion of alcohols to aldehydes or ketones, for example, 

All of the human alcohol dehydrogenases are dimeric zinc metalloenzymes existing in multiple forms that may be homo- or heterodimers with subunits of aproxi-mately 40,000 daltons. Five classes exist in humans and their distribution varies 

Alcohol dehydrogenases metabolize primary alcohols to aldehydes, with n-butanol being the substrate oxidized at the highest rate. Secondary alcohols are oxidized to ketones but at a reduced rate for example, butanol-2 is oxidized at one-third the rate of n-butanol. Tertiary alcohols are not readily oxidized. 

The integrated balance of oxidation and reduction which this process makes possible cannot always be achieved. Yet the recycling of the cofactor is obviously crucial. A second, quite separate reaction can be introduced, for example the oxidation of ethanol to acetaldehyde with an alcohol dehydrogenase. However there is some hope that an electrolytic reduction of the NAD could be developed. This is illustrated by the manufacture of glutathione which is an important thiol-containing peptide. The dimeric disulphide is isolated from yeast cells as a copper complex. This is treated with sulphide to remove the copper, and the free peptide is then reduced at acid pH in the catholyte of an electrolytic half cell. The oxidation of the thiol at the anode is prevented by an ionic membrane which separates the two halves of the cell. 

The reduced glutathione could indirectly provide the reducing power for many enzymatic reductions, but similar processes for the direct electrochemical reduction of NAD are now being developed. If they are successful some powerful catalysts for chemical reduction in aqueous media will become available. 

One such group of catalysts is the alcohol dehydrogenases. These enzymes catalyse the reversible oxidation of a wider range of primary and secondary alcohols than is implied by their names. They are useful because the catalytic specificity of many of them has been well enough studied to make it predictable in the context of substrates which have not been previously treated with the enzymes. Not only can the stereochemistry of the reaction be inferred from the particular dehydrogenase and the intended substrate, but the enzyme most likely to reduce a particular ketone, or oxidize a particular alcohol, can be chosen from the list of those available. For those others whose substrate specificity has not been so clearly delineated, it is easy to test for the oxidation of a particular alcohol, so that its usefulness can be established. 

Only for sorbitol dehydrogenase has the selectivity proved useful in a manufacturing process (section 6.5.1), but for a number of other dehydrogenases the selectivity has been useful as a synthetic tool in chemical research. Where optical centres may be difficult to introduce chemically, the stereospecific reduction of a ketone can be useful, and where enantiomeric 

Quantitative conversions are not difficult to achieve if the necessary cofactors, such as NAD , are held in the reduced form with coupled reactions (see section 6.6.4). What prevents their more widespread acceptance is partly their inability to tolerate the organic solvents in which the alcohols dissolve. On a small scale, the enzymes can be incorporated into aqueous micelles formed with detergents in the solvents. Here they remain active because they are protected within the micelle of water, yet the micelles present a large enough surface area to the organic solvent to allow the rapid transfer of substrate and product between the two phases.  

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Schiff base fonnation, photochemistry, protein partitioning, catalysis by chymotrypsin, lipase, peroxidase, phosphatase, catalase and alcohol dehydrogenase. 

Many biological processes involve oxidation of alcohols to carbonyl compounds or the reverse process reduction of carbonyl compounds to alcohols Ethanol for example is metabolized m the liver to acetaldehyde Such processes are catalyzed by enzymes the enzyme that catalyzes the oxidation of ethanol is called alcohol dehydrogenase... 

The reverse reaction also occurs m living systems NADH reduces acetaldehyde to ethanol m the presence of alcohol dehydrogenase In this process NADH serves as a hydride donor and is oxidized to NAD" while acetaldehyde is reduced... 

Alcohol dehydrogenase (Section 15 11) Enzyme in the liver that catalyzes the oxidation of alcohols to aldehydes and ke tones... 

The Protein Data Bank PDB ID 1A71 Colby T D Bahnson B J Chin J K Klinman J P Goldstein B M Active Site Modifications m a Double Mutant of Liver Alcohol Dehydrogenase Structural Studies of Two Enzyme Ligand Com plexes To be published... 

Alcohol amination Alcoholates Alcohol, commercial Alcohol dehydrogenase... 

Alcohol dehydrogenase (5) and leucine a-ketoglutarate transaminase (33,34) contribute to the development of aroma during black tea manufacturing. Polyphenol oxidase and peroxidase are essential to the formation of polyphenols unique to fermented teas. 

The two oxidoreductase systems most frequentiy used for preparation of chiral synthons include baker s yeast and horse hver alcohol dehydrogenase (HLAD). The use of baker s yeast has been recendy reviewed in great detail (6,163) and therefore will not be coveted here. The emphasis here is on dehydrogenase-catalyzed oxidation and reduction of alcohols, ketones, and keto acid, oxidations at unsaturated carbon, and Bayer-Vidiger oxidations. 

Although alcohol dehydrogenases (ADH) also catalyze the oxidation of aldehydes to the corresponding acids, the rate of this reaction is significantly lower. The systems that combine ADH and aldehyde dehydrogenases (EC 1.2.1.5) (AldDH) are much more efficient. For example, HLAD catalyzes the enantioselective oxidation of a number of racemic 1,2-diols to L-a-hydroxy aldehydes which are further converted to L-a-hydroxy acids by AldDH (166). 

Alcohol dehydrogenase-catalyzed reduction of ketones is a convenient method for the production of chiral alcohols. HLAD, the most thoroughly studied enzyme, has a broad substrate specificity and accommodates a variety of substrates (Table 11). It efficiendy reduces all simple four- to nine-membered cycHc ketones and also symmetrical and racemic cis- and trans-decalindiones (167). Asymmetric reduction of aUphatic acycHc ketones (C-4—C-10) (103,104) can be efficiendy achieved by alcohol dehydrogenase isolated from Thermoanaerohium hrockii (TBADH) (168). The enzyme is remarkably stable at temperatures up to 85°C and exhibits high tolerance toward organic solvents. Alcohol dehydrogenases from horse Hver and T. hrockii... 

Table 11. Alcohol Dehydrogenase-Catalyzed Reductions on Ketones...

Some of the most important aromatic pyrazoles with biological activity are shown in Table 38. Pyrazole itself and several A-unsubstituted pyrazoles are inhibitors and deactivators of liver alcohol dehydrogenase (79JMC356, 79ACS(B)483, B-79MI40414, 82ACS(B)10l). 

U Ryde. Molecular dynamics simulations of alcohol dehydrogenase with a four- or five-coordinate catalytic zinc ion. Proteins 21 40-56, 1995. 

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.)...

The first sequence is from the enzyme citrate synthase, residues 260-270, which form a buried helix the second sequence is from the enzyme alcohol dehydrogenase, residues 355-365, which form a partially exposed helix and the third sequence is from troponin-C, residues 87-97, which form a completely exposed helix. Charged residues are colored red, polar residues ate blue, and hydrophobic residues are green. 

Eklund, H., et al. Three-dimensional structure of horse liver alcohol dehydrogenase at 2.4 A resolution. 

In zero-orrler kinetics, a constant amount of a chemical compound is excreted per unit of rime. In most cases, this phenomenon is caused by the saturation of a rate-limiting enzyme, and the enzyme commonly functions at its maximal rate, i.e., a constant amount of a chemical compound is metabolized per unit time. A good example is ethyl alcohol alcohol dehydrogenase becomes saturated at relatively low concentrations. Because of this saturation, ethyl alcohol is eliminated at a constant rate about 7 g/h. However, rhe reason is not always an enzyme anv... 

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