Nicotinamide adenine dinucleotide liver alcohol dehydrogenase

Zinc-containing alcohol dehydrogenases take up two electrons and a proton from alcohols in the form of a hydride. The hydride acceptor is usually NAD(P) (the oxidized form of nicotinamide adenine dinucleotide (NADH) or its phosphorylated derivative, NADPH). Several liver alcohol dehydrogenases have been structurally characterized, and Pig. 17.8 shows the environment around the catalytic Zn center and the bound NADH cofactor. 

A. Gafni and L. Brand, Fluorescence decay studies of reduced nicotinamide adenine dinucleotide in solution and bound to liver alcohol dehydrogenase, Biochemistry 15, 3165-3171 (1976). 

Alcohol dehydrogenases (ADH EC 1.1.1.1), for which several X-ray structures are available ", catalyze the biological oxidation of primary and secondary alcohols via the formal transfer of a hydride anion to the oxidized form of nicotinamide adenine dinucleotide (NAD ), coupled with the release of a proton. Liver alcohol dehydrogenase (LADH) consists of two similar subunits, each of which contains two zinc sites, but only one site within each subunit is catalytically active. The catalytic zinc is coordinated in a distorted tetrahedral manner to a histidine residue, two cysteine residues and a water molecule. The remaining zinc is coordinated tetrahedrally to four cysteine residues and plays only a structural role . 

Ethylene glycol is used as a freezing-point depressant in automotive antifreeze. It is highly toxic because the enzyme alcohol dehydrogenase and the coenzyme nicotinamide adenine dinucleotide (NAD) oxidize ethylene glycol to much more liver-toxic compounds like glyoxal, hydroxyacetaldehyde, glyoxylic... 

Horse liver alcohol dehydrogenase is a well-documented enzyme capable of operating with high stereoselectivity on a broad structural range of alcohol and carbonyl substrates. The present reaction proceeds via the pathway shown below, where NAD and NADH represent the oxidized and reduced forms, respectively, of the nicotinamide adenine dinucleotide coenzyme. 

Previously, Beckman and co-workers had prepared nicotinamide adenine dinucleotide (NAD) with a fluorophilic ponytail (FNAD). This molecule was able to act as an affinity surfactant and extract the enzyme horse liver alcohol dehydrogenase (HLADH) from an aqueous medium into methoxynona-fluorobutane (HFE) (Figure 7.24). Interestingly, the addition of potential... 

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]. 

Jagodzinski, P. W., Petlcolas, W. L. (1981) Resonance Enhanced Raman Identification of the Zinc-Oxygen Bond in a Horse Liver Alcohol Dehydrogenase-Nicotinamide Adenine Dinucleotide-Aldehyde Transient Chemical Intermediate, J. Am. Chem. Soc. 103, 234-236. 

A number of oxidations and reductions have been carried out in microemulsions using enzymes such as cholesterol oxidase [64,108,109], bilirubin oxidase [110], horseradish peroxidase [111,112], and horse liver alcohol dehydrogenase (HLADH) [73,112-118]. It is noteworthy that cofactor-dependent enzymes also work well in different types of microemulsions. In fact, kinetic studies on the HLDAH-NADH (NADH stands for the reduced form of nicotinamide adenine dinucleotide) system showed that the presence of coenzyme was essential for the long-term stability of the enzyme in a microemulsion [113,115]. 

Jagodzinski PW, Peticolas WL (1981) Resonance enhanced Raman identification of the zinc-oxygen bond in a horse liver alcohol dehydrogenase-nicotinamide adenine dinucleotide-aldehyde transient chemical intermediate. J Am Chem Soc 103 234-236 Jakovac IJ, Goodbrand HB, Lok KP, Jones JB (1982) Enzymes in organic synthesis. 24. Preparations of enantiomerically pure chiral lactones via stereospecific horse liver alcohol dehydrogenase... 

In human liver cells, the enzyme alcohol dehydrogenase (LADH) catalyzes the oxidation of ethanol to yield acetaldehyde. In this reaction, the coenzyme nicotinamide adenine dinucleotide, NAD, is converted to its reduced form, NADH. 

HLADH, horse liver alcohol dehydrogenase (3-NAD, nicotinamide adenine dinucleotide FMN, flavin mononucleotide... 

Horse liver alcohol dehydrogenase (HLADH) catalyzes the oxidoreduction of a variety of compounds [61,62]. It has been demonstrated that HLADH catalyzes the stereospecific oxidation of only one of the enantiopic hydroxyl groups of acyclic and monocyclic me o-diols [63,64]. The oxidation of meso-exo- and enfto-7-oxabicyclo[2.2.1]heptane dimethanol to the corresponding enantiomerically pure y-lactones by HLADH has been demonstrated. Nicotinamide adenine dinucleotide (NAD" ) and flavin adenine dinucleotide (FAD) were required for the stereoselective oxidation of substrate. Due to the high cost of enzyme and required cofactors, this process for preparing chiral lactones was econom-... 

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