Pyridine nucleotide dehydrogenases

V3. Vennesland, B., and Westheimer, F. H., Hydrogen transport and steric specificity in reactions catalyzed by pyridine nucleotide dehydrogenases. In The Mechanism of Enzyme Action (W. D. McElroy, and B. Glass, eds.), pp. 357-379. Johns Hopkins Press, Baltimore, Maryland, 1954. 

The pyridine nucleotide dehydrogenase reactions fall into two large groups those which transfer hydrogen from or to the A (or pro R) side of the 4 position of the nicotinamide ring, and those which use the B (or pro S) side 1.64,65),... 

The liver alcohol dehydrogenase mentioned in the preceding section has the same pro-R stereospecificity for NAD and ethanol as yeast alcohol dehydrogenase. Furthermore, the oxidation of ethanol by a microsomal oxidizing system, or by catalase and H2O2, likewise proceeds with pro-R stereospecificity for the ethanol77>. The catalase-H2C>2 system is so very different, however, from the pyridine nucleotide dehydrogenase, that one wonders whether the similarity in stereospecificity for ethanol is fortuitous. 

It should be noted, in this connection, that there are pyridine nucleotide dehydrogenases which catalyze redox reactions which must occur in two steps. Hydroxymethylglutaryl CoA reductase (discussed on p. 51) is one example. Another is uridine diphosphate-glucose dehydrogenase, which catalyzes the oxidation of the C—6 of the glucose (i.e., a primary alcohol) to a carboxyl group. In both cases, there are two molecules of pyridine nucleotide required, and the overall reactions are essentially irreversible. The former enzyme, with A stereospecificity for the pyridine nucleotide, catalyzes the reduction of an acyl-CoA group... 

The generalization that the same dehydrogenase has the same stereospecificity, no matter what the source of the enzyme, has been tested now particularly well for malic and lactic dehydrogenases. In fact, one can venture a guess, that pyridine nucleotide dehydrogenases which oxidize a-hydroxycarb oxylic acids at the a-position, all have A stereospecificity for the pyridine nucleotide, regardless of their stereo-specificity for the substrate. Biellman and Rosenheimer 88> have assembled the data. One can add liver malic enzyme 90> to their list. 

H20. Hershey, F. B., Lewis, C., Jr., Johnston, G., Mullins, L., and Schiff, T., Effects of heat on pyridine nucleotide dehydrogenases, aldolase, and fumarase of human epidermis. J. Invest. Dermatol. 44, 93-701 (1965). 

Racker to be caused by two pyridine nucleotide dehydrogenases alcohol dehydrogenase and aldehyde dehydrogenase. The product of the oxidation is acetate, and the reaction has not been reversed. A similar... 

The recent review of the pyridine proteins presented by Schlenk makes it unnecessary to present this subject in great detail. Instead we will attempt only to touch on some of the current advances with the partially or highly purified pyridine nucleotide dehydrogenases. A brief summary of the reaction products, coenzyme specificity, source of the enzyme, and its state of purity is given in Table 2. 

RESPIRATORY AND PHOTOSYNTHETIC ELECTRON TRANSPORT IN ANABAENA VARIABILIS LIGHT-DARK ACTIVITIES OF PYRIDINE-NUCLEOTIDE DEHYDROGENASES... 

The mechanism how the pyridine-nucleotide dehydrogenases involved here change their property toward NADPH and NADH by dark/light transitions remains to be clarified. 

Sturzl E, Scherer S and Boger P (1983) Interaction of respiratory and photosynthetic electron transport, and evidence for membrane-bound pyridine-nucleotide dehydrogenases in Anabaena variabilis. Physiol. Plant., submitted. 

FIGURE 18.10 Hydrogen and electrons released in the course of oxidative catabolism are transferred as hydride ions to the pyridine nucleotide, NAD, to form NADH -t- H in dehydrogenase reactions of the type... 

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... 

The carbonyl reductases catalyze reduction of aldehydes and ketones by reduced pyridine nucleotides (NADH and/or NADPH). As mentioned earlier, alcohol dehydrogenase can perform this function in the presence of a high ratio of NADH to NAD+. Other enzymes capable of carbonyl reduction include the aldehyde and ketone reductases. The aldehyde and ketone reductases have a ubiquitous species distribution, with the enzymes present in organisms ranging from bacteria to vertebrates. The mammalian carbonyl reductases have been extensively reviewed (101). 

Fig. 1. General scheme of the hydrogen transfer as catalyzed by dehydrogenase reactions. R represents the residue of the pyridine nucleotide molecule.

Both the enzymes were prepared by a special technique from the insoluble portion of guinea pig liver mitochondria, and they are quite specific with respect to the requirement of pyridine nucleotide (H9, Hll). However, dehydrogenases catalyzing reaction (25) with NAD as coenzyme have been reported (Mil, S13, T3), thus confirming the importance of the source of the enzyme and the purification procedure employed. 

H10. Hochster, R. M., Pyridine nucleotide specificities and rates of formation of G-0-P and of 0-PG dehydrogenases in Aspergillus flavus-oryzae. Arch. Biochem. Biophys. 60, 499-501 (1957). 

R8. Rees, E. D., and Huggins, C., Steroid influences on respiration, glycolysis and levels of pyridine nucleotide linked dehydrogenases of experimental mammary cancers. Cancer Research 20, 963-971 (1960). 

Also, the carboxylation of oxoglutaric acid to form isocitric acid catalyzed by isocitric acid dehydrogenase (ICDH) can be driven electrochemically using methyl viologen as mediator without reduced pyridine nucleotides as cofactors. Thus, electrolysis at — 0.95 V vs SCE of a 0.2 M tris buffer solution (pH 7.7)... 

The ALDs are a subset of the superfamily of medium-chain dehydrogenases/reductases (MDR). They are widely distributed, cytosolic, zinc-containing enzymes that utilize the pyridine nucleotide [NAD(P)+] as the catalytic cofactor to reversibly catalyze the oxidation of alcohols to aldehydes in a variety of substrates. Both endobiotic and xenobiotic alcohols can serve as substrates. Examples include (72) ethanol, retinol, other aliphatic alcohols, lipid peroxidation products, and hydroxysteroids (73). 

The aldehyde dehydrogenases are members of a superfamily of pyridine nucleotide [NAD(P)+]-dependant oxidoreductases that catalyze the oxidation of aldehydes to... 

Flavoprotein dehydrogenases usually accept electrons from reduced pyridine nucleotides and donate them to a suitable electron acceptor. The oxidation-reduction midpoint potential of the FAD of the oxidase has been determined by ESR spectroscopy and shown to be -280 mV. The NADP+/ NADPH redox potential is -320 mV and that of the cytochrome b is -245 mV hence, the flavin is thermodynamically capable of accepting electrons from NADPH and transferring them to cytochrome b. As two electrons are transferred from NADPH, although O2 reduction requires only one electron, the scheme of electron transfer shown in Figure 5.8 has been proposed by Cross and Jones (1991). 

The stereospecificity of hydrogen transfer for estradiol-17 and estradiol-17(3 dehydrogenases has been examined by George et a/.84>. These enzymes are both present in chicken liver, and have substrates which differ only in the chirality of their substituents at C—17. Both of these enzymes were shown to use the 4-pro-S or 4B proton of the NADPH. Since the steroid is a bulky substrate, the authors argue that the steric fit between pyridine nucleotide and steroid cannot be as important as the role played by the enzyme in directing the fit. This paper contains an interesting summary of other recent work on the stereospecificity of pyridine nucleotide dependent-steroid dehydrogenases. 

Liver cells contain two different but closely related enzymes glycerol phosphate dehydrogenase which is specific for NAD, and acylglycerol phosphate dehydrogenase, which is NADP specific. Both enzymes have B stereospecificity for the pyridine nucleotide 93. They apparently have different metabolic functions. 

Pyridine nucleotide-dependent dehydrogenases (ed. H. Sund). Berlin—Heidelberg—New York Springer 1970. 

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