Alcohols dehydrogenase

Horse liver alcohol dehydrogenase (LADH) catalyzes the reversible 

LADH is a zinc metalloenzyme containing 4 zinc atoms per enzyme mole- 

LADH was one of the first native proteins studied by the halide NMR technique [54] and more detailed studies have since then emanated from Ward and co-workers [436 437] as well as from the authors laboratory [431,438-442]. 

Titrations with the reduced coenzyme (NADH) have been performed 

The oxidized coenzyme, NAD, and coenzyme fragments such as adenosines -diphosphor ibose (ADPR) and adenosine-5 -diphosphate and certain coenzyme analogues have also been shown to eliminate the LADH-Cl interaction and detailed titrations with NAD and ADPR have given 

The three subunits alpha or ADH1, beta or ADH2, and gamma or ADH3, are structurally similar. Each consists of 374 amino acids (81). In the context of ethnic comparisons, the most important difference is between 

If the re-oxidation of NADH to cofactor NAD is the rate-limiting step of ethanol oxidation in vivo (82), the different capabilities of alcohol dehydrogenase may not be fully reflected in the elimination rate of ethanol. There are also the possibilities that the effect of the variants depends on ethanol concentration, or that beta2 causes an initial spurt of ethanol oxidation in Orientals which is not seen in Caucasians who have the betai allele and in Blacks who have the beta3 allele. 

The three-dimensional structure of LADH has been reported at 2.4 A resolution and all four zinc atoms exhibit distorted tetrahedral co-ordination. The earlier assignment of the zinc atoms containing a water molecule (or hydroxy-group, 

As previously mentioned, an ADH can be used for the in situ recycling of NAD(P)H cofactors by exploiting the so-called substrate-coupled approach, that is, the coupHng of the reaction of interest with a secondary reaction running in the reverse direction 

The continuous removal of the co-product acetone by a stripping process has been used also on an industrial scale. For example, it has been reported by Wacker Fine Chemicals that by the exploitation of the ISPR approach, the synthesis of (R)-ethyl-3-hydroxybutyrate was achieved in a substrate oupled process catalyzed by the Lactobacillus brevis ADH in the presence of IPA with a yield of 96%, an enantiomeric excess of 99.8%, and a space-time yield of 92 gl d [44]. 

As an alternative to the ISPR approach, the equilibrium of ADH-catalyzed reductions can be shifted by generating thermodynamically stable and kinetically inert co-products, such as y-butyrolactone resulting from the oxidation of the co-substrate 1,4-butanediol (1,4-BD). In a recent communication, it has been shown that only 0.5 equiv of 1,4-BD were necessary to achieve almost complete conversion for the ADH-catalyzed reduction of a-arylpropionaldehydes into the corresponding alcohols, whereas significantly lower conversion was obtained when using comparable amounts of ethanol or IPA as co-substrates [45]. Therefore, it might be foreseen that this approach may reduce the cost and waste product formation in different NAD(P)H-dependent redox processes. 

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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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