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Enzymes liver alcohol dehydrogenase

Figure 3-24. A zinc(ii) complex which acts as a functional model for the hydride transfer reaction which occurs at the active site of the enzyme liver alcohol dehydrogenase. Figure 3-24. A zinc(ii) complex which acts as a functional model for the hydride transfer reaction which occurs at the active site of the enzyme liver alcohol dehydrogenase.
The reduction of NAD+ (and NADP) is reversible, and NADH is itself a reducing agent. We will first look at one of its reactions a typical reduction of a ketone. The ketone is pyruvic acid and the reduction product lactic acid, two important metabolites. The reaction is catalysed by the enzyme liver alcohol dehydrogenase. [Pg.1382]

Hard electrophiles like Mg(C104)2 are used to activate abiotic systems. In the enzyme liver alcohol dehydrogenase (LAD) a considerably different catalytic apparatus is present a zinc ion coordinated to two cysteines and a histidine serves as a coordinating site for the carbonyl compound/alcoholate, as illustrated in equation (10). This zinc ion has amphoteric properties consistent with the capacity to activate the reaction in both directions without being consumed, in other words to act as a catalyst. Synthetic models of this catalytically active zinc have been shown to possess some catalytic activity in analogy to the enzyme (see Section L3.3.5.1iii). [Pg.82]

Al Martini was not able to clear his blood ethanol rapidly enough to stay within the legal limit for driving. Ethanol is cleared from the blood at about Vz ounce/hr (15 mg/dL per hour). Liver metabolism accounts for more than 90% of ethanol clearance from the blood. The major route of ethanol metabolism in the liver is the enzyme liver alcohol dehydrogenase (ADH), which oxidizes ethanol to acetaldehyde with generation of NADH. [Pg.139]

The mechanism of this oxidation for the enzyme liver alcohol dehydrogenase is shown for the reaction of 83, where ethanol is bound to the active site of the enzyme to give 84 via proton abstraction and then hydride transfer to generate acetaldehyde (see 85). NAD+ binds to the active site of the enzyme to induce a conformational change (see Chapter 8 for conformation) to close the active site. The oxidation of ethanol to acetaldehyde (ethanal) is accompanied by reduction of NAD+ to NADH, as shown in the illustration. [Pg.831]

There are instances where reactions are zero-order. An example includes the decomposition of ethyl alcohol in the liver in the presence of the enzyme liver alcohol dehydrogenase. Once again, consider the reaction with the general form... [Pg.573]

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... [Pg.1298]

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. [Pg.114]

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. 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.
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... [Pg.112]

In the classical procedures W, the 5-T or D-labeled mevalonate is converted enzymatically to farnesol, which is then oxidized to famesal by liver alcohol dehydrogenase. This enzyme transfers the pro-R hydrogen of C—1 of ethanol or geraniol (or farnesol) to the 4 pro R position of the nicotinamide ring of NAD. [Pg.55]

In the case of horse liver alcohol dehydrogenase, a homodimeric enzyme, Subramanian et al.(202) used the relative phosphorescence of tyrosine and tryptophan to examine the effects of various ternary complexes known to selectively quench the fluorescence of the tryptophans of each subunit. One proposed quenching mechanism is the formation of a ground-state tyrosinate in a ternary complex at neutral pH.(201) This tyrosinate, by being a resonance... [Pg.50]

S. Subramanian, J. B. A. Ross, L. Brand, and P. D. Ross, Investigation of the nature of enzyme-coenzyme interactions in binary and ternary complexes of liver alcohol dehydrogenase with coenzymes, coenzyme analogs, and substrate analogs by ultraviolet absorption and phosphorescence spectroscopy, Biochemistry 20, 4086-4093 (1981). [Pg.62]

Probably the most extensively studied enzymes are those from alcohol dehydrogenase family. One enzyme from this series which has been thoroughly examined both experimentally and theoretically is liver alcohol dehydrogenase (LADH). It catalyzes the reversible conversion of an alcohol to an aldehyde by transferring hydride from substrate to the cofactor (NAD+) ... [Pg.376]

In the following year, Cleland and his coworkers reported further and more emphatic examples of the phenomenon of exaltation of the a-secondary isotope effects in enzymic hydride-transfer reactions. The cases shown in Table 1 for their studies of yeast alcohol dehydrogenase and horse-liver alcohol dehydrogenase would have been expected on traditional grounds to show kinetic isotope effects between 1.00 and 1.13 but in fact values of 1.38 and 1.50 were found. Even more impressively, the oxidation of formate by NAD was expected to exhibit an isotope effect between 1.00 and 1/1.13 = 0.89 - an inverse isotope effect because NAD" was being converted to NADH. The observed value was 1.22, normal rather than inverse. Again the model of coupled motion, with a citation to Kurz and Frieden, was invoked to interpret the findings. [Pg.41]

Fig. 6 Illustration from Chin and Klinman. Increased catalytic activity of horse-liver alcohol dehydrogenase in the oxidation of benzyl alcohol to benzaldehyde by NAD, measured by cat/ M (ordinate), correlates with the Swain-Schaad exponent for the -secondary isotope effect (abscissa), for which values above about four are indicators of tunneling. This is a direct test of the hypothesis that tunneling in the action of this enzyme contributes to catalysis. As the rate increases by over two orders of magnitude and then levels off, the anomalous Swain-Schaad exponents also increase and then level off. Reproduced from Ref. 28 with the permission of the American Chemical Society. Fig. 6 Illustration from Chin and Klinman. Increased catalytic activity of horse-liver alcohol dehydrogenase in the oxidation of benzyl alcohol to benzaldehyde by NAD, measured by cat/ M (ordinate), correlates with the Swain-Schaad exponent for the -secondary isotope effect (abscissa), for which values above about four are indicators of tunneling. This is a direct test of the hypothesis that tunneling in the action of this enzyme contributes to catalysis. As the rate increases by over two orders of magnitude and then levels off, the anomalous Swain-Schaad exponents also increase and then level off. Reproduced from Ref. 28 with the permission of the American Chemical Society.
Cook, P.F., Oppenheimer, N.J. and Cleland, W.W. (1981). Secondary deuterium and nitrogen-15 isotope effects in enzyme-catalyzed reactions. Chemical mechanism of liver alcohol dehydrogenase. Biochemistry 20, 1817-1825... [Pg.75]

However, a pure enzyme, like horse liver alcohol dehydrogenase (HLADH), shows not only high stereoselectivity but regioselectivity as well, affording, for example, 89% yield of monoalcohol 5 from dione 4 with ee higher than 99% [14]. [Pg.298]

All the enzymes used in the work described above are quite stable at room temperature and can be used in a free form. They can also be used in an immobilized form to improve the stability and to facilitate the recovery. Many immobilization techniques are available today (25). The recent procedure developed by Whitesides et al using water-insoluble, cross-linked poly(aerylamide-acryloxysuccinimide) appears to be very useful and applicable to many enzymes (37). We have found that the non-crosslinked polymer can be used directly for immobilization in the absence of the diamine cross-linking reagent. Reaction of an enzyme with the reactive polymer produces an immobilized enzyme which is soluble in aqueous solutions but insoluble in organic solvents. Many enzymes have been immobilized by this way and the stability of each enzyme is enhanced by a factor of greater than 100. Horse liver alcohol dehydrogenase and FDP aldolase, for example, have been successfully immobilized and showed a marked increase in stability. [Pg.333]

The enzyme chemistry of cyclopropylmethanols has been studied both as inhibitors and mechanistic probes [4, 47]. Thus, a series of alkylcyclopropyl-methanol derivatives have been proved as being inhibitors of horse liver alcohol dehydrogenase. There are two sites in the cyclopropylmethanol inhibitors able of reacting with nucleophiles ... [Pg.12]

Rate experiments that are typically carried out in the presence of different concentrations of an alternative product (or product analog) while using the normal substrates . This approach can be particularly useful when the normal product cannot be used because it is unstable, insoluble, or ineffective (the latter indicated by a very high Ki value). Moreover, the normal product may be consumed as an essential substrate in a coupled assay system for the primary enzyme. Fromm and Zewe used the alternative product inhibition approach in their study of hexokinase. Wratten and Cleland later applied this procedure to exclude the Theorell-Chance mechanism for liver alcohol dehydrogenase. See Abortive Complexes... [Pg.50]

Isotope effects have also been applied extensively to studies of NAD+/NADP+-linked dehydrogenases. We typically treat these enzymes as systems whose catalytic rates are limited by product release. Nonetheless, Palm clearly demonstrated a primary tritium kinetic isotope effect on lactate dehydrogenase catalysis, a finding that indicated that the hydride transfer step is rate-contributing. Plapp s laboratory later demonstrated that liver alcohol dehydrogenase has an intrinsic /ch//cd isotope effect of 5.2 with ethanol and an intrinsic /ch//cd isotope effect of 3-6-4.3 with benzyl alcohol. Moreover, Klin-man reported the following intrinsic isotope effects in the reduction of p-substituted benzaldehydes by yeast alcohol dehydrogenase kn/ko for p-Br-benzaldehyde = 3.5 kulki) for p-Cl-benzaldehyde = 3.3 kulk for p-H-benzaldehyde = 3.0 kulk for p-CHs-benzaldehyde = 5.4 and kn/ko for p-CHsO-benzaldehyde = 3.4. [Pg.406]

Another zinc-utilizing enzyme is carbonate/dehydratase C (Kannan et al., 1972). Here, the zinc is firmly bound by three histidyl side chains and a water molecule or a hydroxyl ion (Fig. 27). The coordination is that of a distorted tetrahedron. Metals such as Cu(II), Co(Il), and Mn(ll) bind at the same site as zinc. Hg(II) also binds near, but not precisely at, this site (Kannan et al., 1972). Horse liver alcohol dehydrogenase (Schneider et al., 1983) contains two zinc sites, one catalytic and one noncatalytic. X-Ray studies showed that the catalytic Zn(II), bound tetrahedrally to two cysteines, one histidine, and water (or hydroxyl), can be replaced by Co(II) and that the tetrahedral geometry is maintained. This is also true with Ni(Il). Insulin also binds zinc (Adams etai, 1969 Bordas etal., 1983) and forms rhombohedral 2Zn insulin crystals. The coordination of the zinc consists of three symmetry-related histidines (from BIO) and three symmetry-related water molecules. These give an octahedral complex... [Pg.49]

AOT/isooctane/ buffer Horse liver alcohol dehydrogenase Microemulsion system that is temperature sensitive to phase separate was used for recovery of proteins and enzymes [283]... [Pg.169]

Horse liver alcohol dehydrogenase (HLADH (E.C. 1.1.1.1), commercially available) is a well-documented enzyme capable of catalyzing the enantioselective oxidation of acyclic and cyclic meso-configurated dimethanol derivatives to chiral lactols and further to the corresponding chiral lactones with high enantioselectivity and in high yield (Table 11) 162 ,69. Incases where the two enantiomeric lactols are formed, a kinetic enantiomer separation can occur in the second oxidation step166. [Pg.636]

Horse liver alcohol dehydrogenase is able to oxidise primary alcohols—except methanol—and to reduce a large number of aldehydes. Aqueous solution or organic solvents can be used [62]. As there are no new developments concerning this enzyme, the reader is referred to the review of Schreier [1]. [Pg.495]

The reduction of 3- and 4-thiepanones (41 and 42) was reported using either hydride (LAH) (67AG(E)872, 70JOC584) or horse liver alcohol dehydrogenase enzymes which gave the 3-hydroxy- (136) and 4-hydroxy- (43) thiepane in optically active form (81CJC1574. ... [Pg.574]


See other pages where Enzymes liver alcohol dehydrogenase is mentioned: [Pg.106]    [Pg.99]    [Pg.106]    [Pg.106]    [Pg.99]    [Pg.106]    [Pg.200]    [Pg.199]    [Pg.233]    [Pg.117]    [Pg.1156]    [Pg.404]    [Pg.372]    [Pg.170]    [Pg.350]    [Pg.94]    [Pg.109]    [Pg.204]    [Pg.131]    [Pg.660]    [Pg.201]    [Pg.639]   


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Alcohol dehydrogenase

Alcohol dehydrogenases

Alcohol liver

Dehydrogenases alcohol dehydrogenase

Enzyme liver

Enzymes alcohol dehydrogenase

Enzymes alcohol dehydrogenases

Enzymes dehydrogenase

Enzymes horse liver alcohol dehydrogenase

Liver alcoholics

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