Alcohol dehydrogenase General

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). 

This zinc metalloenzyme [EC 1.1.1.1 and EC 1.1.1.2] catalyzes the reversible oxidation of a broad spectrum of alcohol substrates and reduction of aldehyde substrates, usually with NAD+ as a coenzyme. The yeast and horse liver enzymes are probably the most extensively characterized oxidoreductases with respect to the reaction mechanism. Only one of two zinc ions is catalytically important, and the general mechanistic properties of the yeast and liver enzymes are similar, but not identical. Alcohol dehydrogenase can be regarded as a model enzyme system for the exploration of hydrogen kinetic isotope effects. 

It is generally recognized that workers exposed to either NG or EGDN have reduced tolerance for alcohol. Animal studies suggest that NG may decrease the activity of alcohol dehydrogenase, thereby decreasing the rate of alcohol metabolism. ... 

In a recent study (54), we showed increased activities of two enzymes of the general phenylpropanoid pathway, PAL and 4-coumarate CoA lig-ase, as well as one enzyme of the specific pathway of lignin biosynthesis, cinnamy 1-alcohol dehydrogenase (CAD), in resistant plants at the time of the hypersensitive host cell death. On the other hand, decreased activities were observed at the same time with susceptible host plants (54). Furthermore, we showed that the well known increase in peroxidase activities, which is strong in resistant and only weak in susceptible plants (55-58), is at least partly due to the increased activity of the lignin biosynthetic pathway (54,59). 

Ethanol is metabolized primarily in the liver by at least two enzyme systems. The best-studied and most important enzyme is zinc dependent alcohol dehydrogenase. Salient features of the reaction can be seen in Fig. 35.1. The rate of metabolism catalyzed by alcohol dehydrogenase is generally linear with time except at low ethanol concentrations and is relatively independent of the ethanol concentration (i.e., zero-order kinetics). The rate of metabolism after ingestion of different amounts of ethanol is illustrated in Fig. 35.2. 

A novel and more general method to enable biocatalyzed conversion and synthesis of hydrophobic compounds involves the use of gel-stabilized aqueous-organic two-phase systems [8], Features, advantages, disadvantages, and perspectives of this method in asymmetric synthesis will be discussed in this chapter, illustrated for the stereoselective benzoin condensation and the reduction of ketones catalyzed by thiamine pyrophosphate (TPP)-dependent lyases and NAD(P)H-dependent alcohol dehydrogenases, respectively. 

One step or two-step transfer Another major question about dehydrogenases is whether the hydrogen atom that is transferred moves as a hydride ion, as is generally accepted, or as a hydrogen atom with separate transfer of an electron and with an intermediate NAD or NADPH free radical. In one study para-substituted benzaldehydes were reduced with NADH and NAD2H using yeast alcohol dehydrogenase as a catalyst.30 This permitted the application of the Hammett equation (Box 6-C) to the rate data. For a series of benzaldehydes for which o+ varied widely, a value... 

In this chapter I will focus on biochemical and molecular aspects leading to lignin production. We have studied in detail phenylalanine ammonia lyase (PAL EC 4.3.1.5), the first enzyme of the general phenylpropanoid pathway, and cinnamyl alcohol dehydrogenase (CAD EC 1.1.1.195), an enzyme specific to the branch pathway leading to lignin formation. 

The biochemical characterization of several alcohol dehydrogenases and their exploitation potential demonstrate that these enzymes are most important tools for biochemists. Amino acid sequences of several ADFls are available so far, and alignment studies allow to establish ADH families and to consider their probable evolutionary relationships. For preparative applications, however, particular properties of an enzyme are essential prerequisites, such as enzyme stability and availability, its substrate specificity, or reaction selectivity. Enzymes with NAD as coenzyme are clearly preferred to NADP-dependent ones in practice, because NAD has a significantly higher stability [186-188], a lower price and, is in general, easier to regenerate. 

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