Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Some enzymatic activities of the glycolytic and hexose monophosphate pathways of Candida parapsilosis, a yeast lacking alcohol dehydrogenase but able to grow on high glucose concentrations, were compared to those of Saccharomyces cerevisiae. Cells were grown either on 8% glucose or on 2% glycerol and activities measured under optimal conditions. Results were as follows: glycolytic enzymes of C. parapsilosis, except glyceraldehyde 3-phosphate dehydrogenase, exhibited an activity weaker than that of S. cerevisiae, especially when yeasts were grown on glycerol. Fructose-1,6 bisphosphatase, an enzyme implicated in gluconeogenesis and in the hexose monophosphate pathway, and known to be very sensitive to catabolite repression in S. cerevisiae, was always active in C. parapsilosis even when cells were grown on 8% glucose. However, the allosteric properties towards AMP and fructose-2,6-bisphosphate were the same in both strains. Glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, two other enzymes of the hexose monophosphate pathway, exhibited a higher activity in C. parapsilosis than in S. cerevisiae. Regulation of two important control points of the glycolytic flux, phosphofructokinase and pyruvate kinase, was investigated. In C. parapsilosis phosphofructokinase was poorly sensitive to ATP but fructose-2,6-bisphosphate completely relieved the light ATP inhibition. Pyruvate kinase did not require fructose-1,6-bisphosphate for its activity, and by this way, did not regulate the glycolytic flux.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative studies on the glycolytic and hexose monophosphate pathways in Candida parapsilosis and Saccharomyces cerevisiae. 283 96

N6-(N-[(4-Azido-3,5,6-trifluoro)pyridin-2-yl]-2-aminoethyl)- adenosine 5'-monophosphate has been synthesized and evidence presented for its structural assignment by ultraviolet and 19F-NMR spectroscopies. Its photolysis was shown to occur within 5 min. This AMP derivative behaves as a competitive inhibitor of NAD+ in horse-liver-alcohol-dehydrogenase-promoted oxidation of ethanol, with a Ki (0.95 mM) comparable to the Ki of AMP (1.9 mM). Moreover it is an activator of the enzyme when nicotinamide ribose is used as the oxidation cofactor. This activation is as good as that promoted by AMP or by the well known 8-azido-AMP. Upon photolysis of this new derivative in the presence of horse liver alcohol dehydrogenase, a covalent enzyme--analogue complex was isolated and assayed as a catalyst in the oxidation of ethanol using nicotinamide ribose as the cofactor. The reaction took place without complementation of AMP, indicating clearly that the AMP analogue is mainly covalently bound in the AMP-binding site, and that the linkage formed between the enzyme and the azido derivative has not dramatically altered the active site of the enzyme. A similar experiment with 8-azido-AMP produced a completely inactive complex.
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PMID:Synthesis and biological activity of N6-(N[(4-azido-3,5,6-trifluoro)-pyridin-2-yl]-2-aminoethyl)-adenosine 5'-monophosphate, a new AMP photoactivatable derivative. Covalent modification of horse liver alcohol dehydrogenase. 291 73

A new adenine nucleotide analog, [3H]pyridoxal 5'-diphospho-5'-adenosine (PLP-AMP), has been synthesized. The effectiveness of PLP-AMP as an affinity probe has been tested using a number of nucleotide-binding enzymes. In comparison to reaction with pyridoxal 5'-phosphate, PLP-AMP binds more tightly and exhibits greater specificity of labeling for most enzymes tested. PLP-AMP is a very potent inhibitor of yeast alcohol dehydrogenase and rabbit muscle pyruvate kinase, with complete inhibition obtained upon incorporation of 1 mol of reagent/mol of catalytic subunit. The reagent is also a potent inhibitor of yeast hexokinase and phosphoglycerate kinase. When modified in the absence of substrates, these enzymes require 2 mol of reagent/mol of active site for complete inhibition. However, when modified in the presence of sugar substrates, this stoichiometry decreases to 1.1 for the hexokinase-glucose complex and 1.4 for the phosphoglycerate kinase . 3-phosphoglycerate complex. The most potent inhibition by PLP-AMP was observed with rabbit muscle adenylate kinase. Half-maximal inhibition was obtained at a concentration of approximately 1 microM. In contrast to these examples, PLP-AMP, as well as pyridoxal 5'-phosphate, fails to act as a potent or specific inhibitor of beef heart mitochondrial F1-ATP-ase. The high specificity of labeling and the ability of nucleotide substrates to decrease the rate of inactivation of the kinases and dehydrogenase are consistent with the modification of active site residues. The complete reversibility of both modification and inactivation in the absence of reduction by NaBH4 and the absorption spectra of modified enzymes prior to and following reduction indicate reaction with lysyl residues. We conclude that PLP-AMP holds considerable promise as an affinity label for exploring the structure and mechanism of nucleotide-binding enzymes.
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PMID:Affinity labeling of nucleotide-binding sites on kinases and dehydrogenases by pyridoxal 5'-diphospho-5'-adenosine. 293 39

We studied the effects of cyclic AMP (cAMP) on HCO-3 transport by rabbit cortical collecting tubules perfused in vitro. Net HCO-3 secretion was observed in tubules from NaHCO3- loaded rabbits. 8-Bromo-cAMP-stimulated net HCO-3 secretion, whereas secretion fell with time in control tubules. Both isoproterenol and vasopressin (ADH) are known to stimulate adenylate cyclase in this epithelium; however, only isoproterenol stimulated net HCO-3 secretion. The mechanism of cAMP-stimulated HCO-3 secretion was examined. If both HCO-3 and H+ secretion were to occur simultaneously in tubules exhibiting net HCO-3 secretion, cAMP might increase the net HCO-3 secretory rate by inhibiting H+ secretion, by stimulating HCO-3 secretion, or both. These possibilities were examined using basolateral addition of the disulfonic stilbene (4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS). In acidifying tubules from NH4Cl-loaded rabbits, DIDS eliminated HCO-3 reabsorption, a result consistent with known effects of DIDS as an inhibitor of H+ secretion. In contrast, cAMP left acidification (H+ secretion) intact. DIDS applied to HCO-3 secretory tubules failed to increase the HCO-3 secretory rate, indicating minimal H+ secretion in HCO-3 secreting tubules. Thus, inhibition of H+ secretion by cAMP could not account for the cAMP-induced stimulation of net HCO-3 secretion. cAMP-stimulated HCO-3 secretion was reversibly eliminated by 0 Cl perfusate, whereas luminal DIDS had no effect. Bath amiloride (1 mM) failed to eliminate cAMP-stimulated HCO-3 secretion when bath [Na+] was 145 mM or 5 mM. cAMP depolarized the transepithelial voltage. The collected fluid [HCO-3] after cAMP could be accounted for by electrical driving forces, suggesting that cAMP stimulates passive HCO-3 secretion. However, cAMP did not alter HCO-3 permeability measured under conditions expected to inhibit transcellular HCO-3 movement (0 Cl- solutions and bath DIDS). This measured HCO-3 permeability was not high enough to account, by passive diffusion, for the HCO-3 fluxes observed in Cl-containing solutions. We conclude the following: cAMP increased net HCO3- secretion by stimulating HCO3- secretion and not by inhibiting H+ secretion; this HCO3- secretion may have occurred by Cl-HCO3- exchange; Na+-H+ exchange appeared not to play a role in basolateral H+ extrusion under these conditions; and the stimulation of HCO3- secretion by isoproterenol, but not ADH, suggests the existence of separate cell cAMP pools or cellular heterogeneity in this cAMP response.
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PMID:Cyclic adenosine monophosphate-stimulated bicarbonate secretion in rabbit cortical collecting tubules. 298 40

Phenothiazines and W7, calmodulin antagonists, inhibit the water flow response produced by ADH, exogenous cyclic AMP, phosphodiesterase inhibition and serosal hypertonicity. Calmodulin antagonists had no effect on osmotic water movement in the absence of hormone. Calmodulin was isolated and localized by immunofluorescence in bladder epithelial cells. Phenothiazines inhibited toad bladder calmodulin activation of phosphodiesterase and prevented fluorescent antibody recognition. The results suggest that the calcium-calmodulin process plays a role in the hydro-osmotic response to ADH and that produced by serosal hypertonicity. The calmodulin common site occurs subsequent to cyclic AMP formation, perhaps on the microtubule-microfilament system.
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PMID:Inhibition of the hydro-osmotic response to vasopressin and hypertonicity by phenothiazines and W7, calmodulin antagonists. 299 93

Binding of NAD coenzymes to yeast alcohol dehydrogenase (YADH) and porcine heart lactate dehydrogenase (PHLDH) was studied by hydrogen-deuterium exchange with the infrared technique. Conformational changes in the enzymes specific to the coenzymes and their fragments were observed, and the pH dependence of the exchange reaction shows that it conforms to the EX-2 scheme. In both YADH and PHLDH the magnitude of the conformational change of measured by exchange retardation is considerably larger for NAD+ than for NADH. Studies with coenzyme fragments like ADP-ribose, ADP, and AMP also highlight the lack of rigorous correlation between structural features such as charge and size and their influence on exchange behavior. Ternary complexes such as YADH-NAD+-pyrazole, PHLDH-NAD+-oxalate, and PHLDH-NADH-oxamate, which mimic the transition state, have a significantly more pronounced effect on exchange rates than the corresponding binary complexes. The outstanding feature of this study is the demonstration that in the binary enzyme-coenzyme complexes the more loosely bound NAD+ is more effective in retarding exchange than the more firmly bound NADH. These differences are attributed to the unequal structural constraints exerted by the two coenzymes upon the enzymes, which translate to unequal expenditure of transconformational work in the formation of the two complexes. The opposing variation in the free energy of binding and the transconformational work expended can be viewed as an unequal partitioning of the net free energy gain resulting from the protein-ligand interaction into a binding term and that required for conformational change.
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PMID:Interdependence of coenzyme-induced conformational work and binding potential in yeast alcohol and porcine heart lactate dehydrogenases: a hydrogen-deuterium exchange study. 331 Nov 54

Previous studies have shown that captopril (CP) inhibits ADH-stimulated osmotic water permeability (Pf) in the toad bladder by potentiating endogenous bradykinin (BK). The present studies examine the effect of CP on ADH-stimulated Pf in isolated, perfused rabbit cortical collecting tubules (CCT). CP (10(-4) M) reversibly inhibited Pf, stimulated by maximal concentrations of ADH (10 microU/ml). Pretreatment of CCT's with 5 microM indomethacin, however, abolished the effect of CP. Inhibition of BK production by the kallikrein inhibitors, aprotinin and benzamidine, failed to enhance Pf stimulated by submaximal concentrations of ADH (2.5 microU/ml). Since ADH exerts its effects by activation of adenylyl cyclase (AC), further experiments were performed to identify the site at which CP inhibits this cascade. CP significantly inhibited forskolin (10(-4) M) stimulated Pf; however, it had no effect on cyclic AMP (10(-5) M) stimulated Pf, suggesting that the site of action is on the catalytic subunit or one of the GTP regulatory proteins of AC. To further localize the site of CP's action, CCT's were pre-incubated with pertussis toxin (0.5 microgram/ml) to inactivate the inhibitory, guanosine triphosphate (GTP) regulatory protein, Gi. In these tubules, CP failed to inhibit the action of ADH. We conclude that CP stimulates prostaglandin production which in turn activates Gi and inhibits AC activity. We further suggest that CP stimulates PG's directly, not via BK.
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PMID:Captopril inhibits the hydroosmotic effect of ADH in the cortical collecting tubule. 332 2

On- and off-velocity constants for NADH and NAD+ binding to liver alcohol dehydrogenase in the pH range 10-12 have been determined by stopped-flow kinetic methods. The results are consistent with previously reported equilibrium binding data and proposals attributing the main effects of pH on coenzyme binding to ionization of Lys-228 and zinc-bound water. Deprotonation of the group identified as Lys-228 decreases the NADH and NAD+ association rates by a factor exceeding 20 and has no detectable effect on the coenzyme dissociation rates in the examined pH range. Ionization of the group identified as zinc-bound water causes a 3-fold increase of the rate of NADH dissociation from the enzyme, and decreases the rate of NAD+ dissociation by a factor of 200. The NADH and NAD+ association rates are decreased by a factor of 30 and 5, respectively. The observed effects of pH can be rationalized in terms of electrostatic interactions of the ionizing groups with the charges present on the coenzyme molecules and lend support to the idea that binding of the coenzyme nicotinamide ring occurs subsequent to binding of the AMP portion of the coenzyme.
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PMID:Kinetics of coenzyme binding to liver alcohol dehydrogenase in the pH range 10-12. 359 10

The highly active alcohol dehydrogenase (EC 1.1.1.1) in rat hepatic tumor cells (HTC) was purified 120-fold by chromatography on DEAE-Sepharose and AMP-Agarose to yield an enzyme with a specific activity of 88 mumole/min/mg protein, assayed with 1.7 mM NAD+ and 0.55 M ethanol at pH 9 and 30 degrees C. (By comparison, purified, normal rat liver enzyme has an activity of about 1 unit/mg.) Based on its physical and kinetic properties, we conclude that the HTC isozyme is the same as the enzyme from rat stomach and another rat hepatoma (Cederbaum AI, Pietruszko R, Hempel J, Becker FF, and Rubin E (1975) Arch Biochem Biophys 171:348-360). The kinetics of the HTC enzyme are consistent with the Ordered Bi Bi mechanism. The kinetic constants are generally much larger for the HTC enzyme than for the normal rat liver enzyme. The Michaelis constants for ethanol and acetaldehyde (Kb = 1100 mM, Kp = 260 mM) are 1000-fold larger, and the constants for NADH are 10 to 50-fold larger. Although the HTC enzyme has low catalytic efficiency (V/Kb) on ethanol, it has much better activity on longer chain alcohols, but no activity on cyclohexanol. The pH dependence of V/Kb with ethanol is unusual in that it appears to be a linear function of pH, increasing with a slope of 0.56. Thus, the active sites of the liver and HTC enzymes may be different, although the HTC enzyme is inactivated by bromoacetate and bipyridine as is found for the liver enzyme. The HTC (stomach) enzyme may function to oxidize high concentrations of ingested ethanol or longer chain alcohols.
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PMID:Characterization of alcohol dehydrogenase from cultured rat hepatoma (HTC) cells. 361 21

The interaction of NAD(H)-dependent dehydrogenases--yeast alcohol dehydrogenase and rabbit muscle lactate dehydrogenase--with reactive dyes produced in the USSR was studied. The essential role of metal ions in specific binding of alcohol dehydrogenase and dyes was demonstrated by differential spectroscopy, circular dichroism spectroscopy and chromatography. Lactate dehydrogenase in contrast with alcohol dehydrogenase does not require metal ions for the binding of the above-said dyes. A comparative study of eluting abilities of selected desorption agents (imidazole, adenine, 8-oxyquinoline-5-sulfonic acid, NAD, AMP, EDTA) by alcohol dehydrogenase chromatography on adsorbents with light-resistant yellow 2KT-Cu(II) and orange 5K revealed the differences in competition of the dyes for NAD-binding sites of alcohol dehydrogenase. The participation of light-resistant yellow 2KT-Cu(II) in the formation of mixed complexes with imidazole, adenine, 8-oxyquinoline-5-sulfonic acid, NAD and EDTA suggests that the specific binding of alcohol dehydrogenase to light-resistant yellow 2KT-Cu(II) is due to coordination between the Cu(II) ion and the amino acid residue in alcohol dehydrogenase.
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PMID:[Interaction of NAD(H)-dependent dehydrogenases with active dyes and their complexes with transitional metal ions]. 381 55


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