Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alkylation at N-1 of the NAD+ adenine ring with 3,4-epoxybutanoic acid, followed by chemical reduction to the alkali-stable NADH form and alkaline Dimroth rearrangement, gave the NADH derivative alkylated at the exocyclic adenine amino group. Enzymic reoxidation of the latter derivative gave nicotinamide-6-(2-hydroxy-3-carboxypropylamino)purine dinucleotide, a functionalized NAD+ analogue carrying an omega-carboxyalkyl side-chain at the exocyclic adenine amino group. Carbodiimide coupling of the latter derivative to high-molecular-weight water-soluble (polyethyleneimine, polylysine) and insoluble (aminohexyl-Sepharose) polymers gave the corresponding macromolecularized NAD+ analogues. These derivatives have been shown to be enzymically reducible. The polyethyleneimine and polylysine analogues showed a substantial degree of efficiency relative to free NAD+ with rabbit muscle lactate dehydrogenase (60 and 25% respectively) but a lower one with yeast alcohol dehydrogenase and Bacillus subtilis alanine dehydrogenase (2-7%). The polyethyleneimine derivative entrapped in cellulose triacetate fibres together with the lactate dehydrogenase was operationally stable during repetitive use.
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PMID:Synthesis of coenzymically active soluble and insoluble macromolecularized NAD+ derivatives. 17 91

The initial metabolic products of cyclophosphamide (4-hydroxy-cyclophosphamide and aldophosphamide) were prepared biologically in unpurified form. Their toxicity to tumor cells were tested by bioassay techniques and in cell culture, and the deactivation abilities of various tissue-soluble fractions were quantitated. Liver and kidney cytosol effectively deactivated the primary metabolites, whereas cytosols from gastrointestinal tract mucosa, Walker ascites tumor, and spleen were less efficient. When [14C]cyclophosphamide was activated and incubated with liver cytosol, 34% of all radioactivity was identified as carboxyphosphamide, by mass spectrometry of the methyl ester. Measurement of alcohol dehydrogenase (EC 1.1.1.1) and aldehyde dehydrogenase (EC 1.2.1.3) activities by reduced nicotinamide adenine dinucleotide production revealed a qualitative correspondence between aldehyde dehydrogenase activity and deactivation ability. Unpurified aldophosphamide and the analogs prepared from 6-methyl- and 5,5-dimethylcyclophosphamides were substrates for nicotinamide adenine dinucleotide-requiring enzymes, whereas incubation of 4-hydroxy-4-methylcyclophosphamide in an unfractionated incubation mixture with liver soluble enzymes did not cause reduced nicotinamide adenine dinucleotide production.
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PMID:The enzymatic basis of the selective action of cyclophosphamide. 17 33

The fluorescence of the natural coenzyme, NADH, is used to monitor the environment of the nicotinamide moiety at the active centre of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12). Changes of the fluorescence quantum yield and polarization of a small amount of NADH, totally bound by an excess of enzyme, show that at half-saturation of the oligomer with NAD a conformational change is induced which affects the active centre regions of the remaining subunits. This conformational transition is not effected by adenosine diphosphoribose, suggesting that the binding of the nicotinamide moiety of NAD to two subunits is essential for the change of tertiary structure of the remaining subunits that causes the observed changes of the fluorescence properties of the ADH "tracer probe". It is suggested that this conformational transition of the oligomer is responsible for the major decrease of affinity for NAD which occurs at half-saturation, and possibly for the activation by NAD+ of the reductive dephosphorylation reaction catalysed by the enzyme. It is also suggested, by analogy with haemoglobin, that the molecular basis of the negative cooperativity may be the creation of additional intersubunit bonds during the binding of the first two NAD molecules to the tetramer, and a change from a "relaxed" quaternary structure to a "tense" structure at half-saturation.
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PMID:Conformational changes of glyceraldehyde-3-phosphate dehydrogenase induced by the binding of NAD. A unified model for positive and negative cooperativity. 17 91

Reaction in dimethyl sulfoxide of nicotinamide 8-bromoadenine dinucleotide with the disodium salt of 3-mercaptopropionic acid afforded nicotinamide-8-(2-carboxyethylthio)adenine dinucleotide, a new NAD+ analogue functionalized at the adenine C-8 position by an omega-carboxylic side chain. Carbodimide coupling of the latter derivative to high-molecular-weight water-soluble (polyethyleneimine, polylysine) and insoluble (aminohexy)-Sepharose) polymers gave the corresponding macromolecular NAD+ analogues. These derivatives have been shown to be enzymically reducible. The polyethyleneimine analogue showed a substantial degree of efficiency relative to free NAD+ with yeast alcohol dehydrogenase (47%) but a considerably lower one with rabbit muscle lactate dehydrogenase (3%); the polylysine analogue showed a low degree of efficiency with both enzymes (5-6%).
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PMID:New coenzymically-active soluble and insoluble macromolecular NAD+ derivatives. 17 13

A new NAD -isomer was prepared, in which the D-ribose of the adenosine moiety was substituted by the enantiomeric L-ribose. As compared to nicotinamide-adenine-dinucleotide (NAD) and NADH the coenzyme isomer (D,L)-NAD and its dihydroform (D,L)-NADH are far less tightly bound to lactate dehydrogenase and alcohol dehydrogenase from horse liver. In the presence of the second substrate (D,L)-NAD and (D,L)-NADH act as hydrogen acceptor and hydrogen donator, respectively, with lactate dehydrogenase and alcohol dehydrogenases from horse liver and yeast. Compared to NAD and NADH the Michaelis constants are always increased, the catalytic constants (V/Et) were found to be decreased except for the dihydroform reacting with alcohol dehydrogenase from liver.
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PMID:Interaction between dehydrogenases and a new NAD -isomer. 17 98

We have identified an alcohol dehydrogenase activity in Pseudomonas putida strains carrying the CAM-OCT degradative plasmid that were grown on octane. The activity is nicotinamide adenine dinucleotide independent, sediments at 48,000 x g, and shows 20-fold greater activity with octanol rather than butanol as substrate. The enzyme is inducible by unoxidized alkane and is present only in strains that have the OCT plasmid genes for alkane degradation with a wild-type alcO locus. No analogous chromosomal dehydrogenase could be detected. Wild-type and actanol-negative mutants (alcA-) without plasmids both contain a constitutive nicotinamide adenine dinucleotide-linked soluble alcohol dehydrogenase activity. This means that alcA- mutants are cryptic for octanol oxidation and suggests that the particulate plasmid-coded alcohol dehydrogenase activity is active on surface- or membrane-bound substrate.
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PMID:Plasmid-determined alcohol dehydrogenase activity in alkane-utilizing strains of Pseudomonas putida. 17 5

The preparation of model compounds 1-(2',6'-dichlorobenzyl)-3-halogenopyridinium and the study of their properties were achieved. Their chemical reduction to the corresponding 1,4-dihydropyridines is proved by spectroscopic analysis. 3-Iodopyridine--adenine dinucleotide was prepared by enzymic transglycosidation while the 3-chloro, 3-bromo and 3-iodo pyridine--adenine dinucleotides were synthesized from 3-amino-pyridine--adenine dinucleotide. The 3-halogenopyridine--adenine dinucleotides were proved to be active as hydrogen acceptors with alcohol as a substrate. The absorption band at 290 nm of cinnamaldehyde appeared to be a very sensitive tool for studying the enzymic reaction. With the alcohol dehydrogenase from yeast, only slight activity was detected. 3-Halogenopyridine--adenine dinucleotides are competitive inhibitors with respect to nicotinamide--adenine dinucleotide with alcohol dehydrogenase from yeast, lactate dehydrogenase and malate dehydrogenase. The use of 3-iodopyridine--adenine dinucleotide as a heavy-atom derivative for X-ray structure determination is proposed.
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PMID:Preparation and properties of 3-halopyridine--adenine dinucleotides, NAD+ analogues and model compounds. 17 12

The synthesis of 5-(2-oxalylethyl)-NADH, a reduced nicotinamide adenine dinucleotide (NADH) derivate with pyruvate covalently attached to the 5 position of the dihydronicotinamide ring over an additional methylene group has been described previously (Trommer, W.E., Blume, H., and Kapmeyer, H. (1976) Justus Liebigs Ann. Chem., 848). In the presence of lactate dehydrogenase, the dihydropyridine ring of this coenzyme-substrate analogue is oxidized and the carbonyl function of the side chain is reduced to the corresponding L-hydroxy derivative with a maximum velocity of 1/3000 of the natural reaction. This reaction is intramolecular as shown by competition experiments with pyruvate. 5-(2-oxalylethyl)-NADH (pyr-NADH) appears to be a true transition state analogue, proving its postulated structure. Pyr-NADH is high specific for this enzyme as demonstrated by the facts that (1) D-lactate dehydrogenase does not catalyze the intramolecular redox reaction, although the substrate moiety of pyr-NADH is reduced in the presence of NADH; (2) when tested with malate dehydrogenase, alcohol dehydrogenase, glyceraldehyde phosphate dehydrogenase,glycerate dehydrogenase, and glycerol dehydrogenase pyr-NADH is not even oxidized in the presence of the corresponding substrates. However, a great similarity between the transition states of the reduction of pyruvate catalyzed by lactate dehydrogenase and alanine dehydrogenase could be shown. Alanine dehydrogenase catalyzes the intramolecular redox reaction as well. In the presence of ammonium ions, pyr-NADH is transformed to 5-(3-carboxyl-3-aminopropyl)-NAD+.
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PMID:A transition state analogue for two pyruvate metabolizing enzymes, lactate dehydrogenase and alanine dehydrogenase. 18

We have studied the binding of the enzymatically active NAD+ analogue, 3-iodopyridine-adenine dinucleotide, and the inactive analogue, pyridine-adenine dinucleotide to the enzyme horse liver alcohol dehydrogenase using X-ray crystallographic methods. These studies were made under such conditions that crystals of the complexes were isomorphous to apoenzyme crystals. Both analogues bind in the same conformation. The binding of the adenosine moiety is very similar to that of ADP-ribose or NADH bound to the enzyme. The conformation and mode of binding of the remaining portions of the analogue molecules is, however, quite different. The pyridine ring is not situated in the active-site pocket as the nicotinamide group in the isomorphous enzyme-NADH-imidazole complex but lies at the surface of the crevice between the two domains of the subunit, approximately 1.5 nm away from the catalytically active zinc atom. Lys-228 which has been shown to be important for NADH dissociation is in this region of the molecule.
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PMID:The crystal structure of complexes between horse liver alcohol dehydrogenase and the coenzyme analogues 3-iodopyridine-adenine dinucleotide and pyridine-adenine dinucleotide. 20 59

The CD (circular dichroism) and CPL (circular polarization of luminescence) spectra of NADPH in aqueous solution were studied and found to be markedly different. The spectra were not affected by cleavage of the coenzyme molecule with phosphodiesterase. The differences are thus not due to the existence of extended and folded conformations of NADPH and it is concluded that they originate in excited state conformational changes of the nicotinamide--ribose fragment. Opposite signs of both the CD and CPL spectra were observed for NADH bound to horse liver alcohol dehydrogenase and to beef heart lactate dehydrogenase indicating structural differences between the nicotinamide binding sites. The binding of substrate analogues to enzyme--coenzyme complexes did not affect the CD spectra and hence no significant conformational changes are induced upon formation of the ternary complexes. No changes in the CPL spectrum of NADH bound to lactate dehydrogenase were observed upon adding oxalate to form the ternary complex. Marked differences were found between the CPL spectra of binary and ternary complexes with liver alcohol dehydrogenase, while the CD spectra of these complexes were identical. It is concluded that a conformational change of the excited NADH molecule occurs in the binary but not in the ternary complex involving LADH, thus indicating an increased rigidity of the latter complex.
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PMID:Circular dichroism and circular polarization of luminescence of reduced nicotinamide adenine dinucleotide in solution and bound to dehydrogenases. 20 11


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