Liver alcohol dehydrogenase

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... 

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). 

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

ADH Horse liver alcohol dehydrogenase, an enzyme dimer of identical 374 amino acid polypeptide chains. The amino acid composition of ADH is reasonably representative of die norm for water-solnble proteins. 

FIGURE 6.41 The quaternary structure of liver alcohol dehydrogenase. Within each subunit is a six-stranded parallel sheet. Between the two subunits is a two-stranded antiparallel sheet. The point in the center is a C9 symmetry axis. (Jane Richardson)... 

Liver alcohol dehydrogenase (ADH) is relatively nonspecific and will oxidize ethanol or other alcohols, including methanol. Methanol oxidation yields formaldehyde, which is quite toxic, causing, among other things, blindness. Mistaking it for the cheap... 

FIGURE 16.13 Liver alcohol dehydrogenase catalyzes the transfer of a hydride ion (H ) from NADH to acetaldehyde (CH3CHO), forming ethanol (CH3CH9OH). 

Figure 8.27 Reduction of aldehyde in SCCO2 by an isolated enzyme, horse liver alcohol dehydrogenase (HLADH) [20c] (a) Reaction scheme (b) fluorinated coenzyme soluble in CO2 and (c) effect of coenzyme on the reaction.

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. 

Figure 17.8 Catal3ftic zinc center of horse liver alcohol dehydrogenase revealed from an X-ray crystallographic structure (PDB file 20HX) [Al-Karadaghi et al., 1994]. The bound NADH cofactor, a molecule of the inhibitor dimethylsulfoxide (DMSO), and the amino acid residues that coordinate the Zn are shown as sticks shaded according to the elements, and the Zn center is shown as a gray sphere, while the protein is shown in thin gray lines.

Al-Karadaghi S, Cedergren-Zeppezauert ES, HovmoUer S. 1994. Refined crystal structure of liver alcohol dehydrogenase-NADH complex at 1.8 A resolution. Acta Crystallogr DSO 793 - 807. 

Diol bonded silica Glucosamine, bovine serum albumin, immunoglobulin, acetylcholine esterase, horse liver alcohol dehydrogenase [136]... 

Liver Alcohol Dehydrogenase Models with Mixed Donor Ligands 1228... 

For a liver alcohol dehydrogenase (LADH) model an NS2O coordination sphere is required. The chelating aldehydes are ideal for the formation of this donor set when combined with bis(pentafluoro-thiophenolato)zinc. Structural data on the complexes with one equivalent of 6-methylpyridine-2-carbaldehyde, 6-methoxypyridine-2-carbaldehyde, 2-(dimethylamino)benzal-dehyde) demonstrate that the coordination sphere for LADH has been reproduced to a close approximation and the corresponding alcohol complexes have also been characterized.354 Other thiophenols have been used to form such complexes but have not been structurally characterized.304... 

Fig. 7. Horse-liver alcohol dehydrogenase (HLADH) catalyzed alcohol oxidation at a graphite felt anode modified by poly(acrylic acid) (PAA) under coimmobilization of ferrocene derivatives (Fc), diaphorase (Dp), and HLADH [39]...

We then coupled the regeneration system 1 to the horse liver alcohol dehydrogenase (HLADH) catalyzed oxidation of cyclohexanol to cyclohexanone as a model system (Fig. 9). 

Recently, we adopted the same system for the reduction of 4-phenyl-2-butanone to (S)-4-phenyl-2-butanol using the NADH-dependent horse liver alcohol dehydrogenase (HLADH) and S-ADH from Rhodococcus sp [68] with high enantioselectivity (Fig. 17) [69]. As mediator, we applied the low-molecular... 

Several approaches have been undertaken to construct redox active polymermodified electrodes containing such rhodium complexes as mediators. Beley [70] and Cosnier [71] used the electropolymerization of pyrrole-linked rhodium complexes for their fixation at the electrode surface. An effective system for the formation of 1,4-NADH from NAD+ applied a poly-Rh(terpy-py)2 + (terpy = terpyridine py = pyrrole) modified reticulated vitreous carbon electrode [70]. In the presence of liver alcohol dehydrogenase as production enzyme, cyclohexanone was transformed to cyclohexanol with a turnover number of 113 in 31 h. However, the current efficiency was rather small. The films which are obtained by electropolymerization of the pyrrole-linked rhodium complexes do not swell. Therefore, the reaction between the substrate, for example NAD+, and the reduced redox catalyst mostly takes place at the film/solution interface. To obtain a water-swellable film, which allows the easy penetration of the substrate into the film and thus renders the reaction layer larger, we used a different approach. Water-soluble copolymers of substituted vinylbipyridine rhodium complexes with N-vinylpyrrolidone, like 11 and 12, were synthesized chemically and then fixed to the surface of a graphite electrode by /-irradiation. The polymer films obtained swell very well in aqueous... 

Modelling the effects of Ser-48 in the hydride transfer step of liver alcohol dehydrogenase,... 

Theorell, H. and Chance, B. (1951). Studies on liver alcohol dehydrogenase, Acta Chem. Scand., 5, 1127-1144. 

Figure 12.6 (a) The catalytic site of liver alcohol dehydrogenase and (b) the essential features of its catalytic cycle. (Reprinted with permission from Parkin, 2004. Copyright (2004) American Chemical Society.)... 

---