Alcohol dehydrogenases oxidative reactions

Deviations from equation (57) have also been used to demonstrate that tunnelling is important in the enzyme-catalysed oxidation of benzyl alcohol to benzaldehyde by NAD+ and yeast alcohol dehydrogenase (YADH) (reaction (60)) (Cha et al., 1989 Klinman, 1991). 

Figure 16.12. Maintaining Redox Balance. The NADH produced by the glyceraldehyde 3-phosphate dehydrogenase reaction must be reoxidized to NAD+ for the glycolytic pathway to continue. In alcoholic fermentation, alcohol dehydrogenase oxidizes NADH and generates ethanol. In lactic acid fermentation (not shovm), lactate dehydrogenase oxidizes NADH while generating lactic acid.

A single enzyme is sometimes capable of many various oxidations. In the presence of NADH (reduced nicotinamide adenine dinucleotide), cyclohexanone oxygenase from Acinetobacter NCIB9871 converts aldehydes into acids, formates of alcohols, and alcohols ketones into esters (Baeyer-Villiger reaction), phenylboronic acids into phenols sulfides into optically active sulfoxides and selenides into selenoxides [1034], Horse liver alcohol dehydrogenase oxidizes primary alcohols to acids (esters) [1035] and secondary alcohols to ketones [1036]. Horseradish peroxidase accomplishes the dehydrogenative coupling [1037] and oxidation of phenols to quinones [1038]. Mushroom polyphenol oxidase hydroxylates phenols and oxidizes them to quinones [1039]. 

Geotrichum candidum NAD" " alcohol dehydrogenase (Oxidized form of coenzyme) catalyzes both reactions... 

Given that transaminases are not able to aminate alcohols, one possibility for the synthesis of chiral amino alcohols is an enzyme cascade reaction carried out with whole cells [36]. Three enz3nnes cascaded in series were expressed in E. colt first the alcohol dehydrogenase oxidized tiie alcohol to the corresponding aldehyde, which is converted into the amine by the transaminase as shown in Scheme 29.15. The recycling of pyruvate and cofactor regeneration were achieved by the alanine 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... 

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). 

Step 3 of Figure 29.12 Oxidation and Decarboxylation (2K,3S)-lsocitrate, a secondary alcohol, is oxidized by NAD+ in step 3 to give the ketone oxalosuccinate, which loses C02 to givea-ketoglutarate. Catalyzed by isocitrate dehydrogenase, the decarboxylation is a typical reaction of a /3-keto acid, just like that in the acetoacetic ester synthesis (Section 22.7). The enzyme requires a divalent cation as cofactor, presumably to polarize the ketone carbonyl group. 

Formally, in redox reactions there is transfer of electrons from a donor (the reductant) to the acceptor (the oxidant), forming a redox couple or pair. Oxidations in biological systems are often reactions in which hydrogen is removed from a compound or in which oxygen is added to a compound. An example is the oxidation of ethanol to acetaldehyde and then to acetic acid where the oxidant is NAD. catalyzed by alcohol dehydrogenase and acetaldehyde dehydrogenase, respectively. 

Reaction temperature is one of the parameters affecting the enantioselectivity of a reaction [16]. For the oxidation of an alcohol, the values of kcat/fQn were determined for the (R)- and (S)-stereodefining enantiomers E is the ratio between them. From the transition state theory, the free energy difference at the transition state between (R) and (S) enantiomers can be calculated from E (Equation 2), and AAG is in turn the function of temperature (Equation 3). The racemic temperature (% ) can be calculated as shown in (Equation 4). Using these equations, % for 2-butanol and 2-pentanol of the Thermoanaerobacter ethanolicus alcohol dehydrogenase were determined to be 26 and 77 °C, respectively. 

Figure 17.19 A membianeless ethanol/02 enz3fme fuel cell. Alcohol dehydrogenase and aldehyde dehydrogenase catalyze a stepwise oxidation of ethanol to acetaldehyde and then to acetate, passing electrons to the anode via the mediator NAD+/NADH. At the carhon cathode, electrons are passed via the [Ru(2,2 -bipyridyl)3] and biUverdin/bilimbin couples to bilirubin oxidase, which catalyzes O2 reduction to H2O. (a) Schematic representation of the reactions occruring. (b) Power/cmrent response for the ceU operating in buffered solution at pH 7.15, containing 1 mM ethanol and 1 mM NAD. Panel (b) reprinted from Topcagic and Minteer [2006]. Copyright Elsevier, 2006.

The reaction is reversible and when the relative concentration of ethanol is high, alcohol dehydrogenase carries out the oxidation of ethanol => alcohol dehydrogenase is important in detoxication. 

Alcohol dehydrogenases catalyze oxidation of alcohols in a reaction dependent on the pyridine nucleotide NAD+ [Eq. (5)]. Since the reaction is reversible, alcohol dehydrogenases also catalyze the reduction of aldehydes by... 

While most alkaloids do not contain aldehydes when they enter mammalian, microbial, or plant tissues, this functional group may become important when formed as a metabolite of alcohols (via alcohol dehydrogenase) or amines (via oxidative dealkylation and oxidative deamination). Aldehyde dehydrogenases catalyze oxidation of aldehydes to the corresponding carboxylic acids. The physical properties, catalytic mechanism, and specificity of this group of enzymes has been reviewed (99). The general reaction catalyzed by aldehyde dehydrogenase is seen in Eq. (9). 

Since many of the transformations undergone by metabolites involve changes in oxidation state, it is understandable that cofactors have been developed to act as electron acceptors/ donors. One of the most important is that based on NAD/NADP. NAD+ can accept what is essentially two electrons and a proton (a hydride ion) from a substrate such as ethanol in a reaction catalysed by alcohol dehydrogenase, to give the oxidized product, acetaldehyde and the reduced cofactor NADH plus a proton (Figure 5.2). Whereas redox reactions on metal centres usually involve only electron transfers, many oxidation/reduction reactions in intermediary metabolism, as in the case above, involve not only electron transfer but... 

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