Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT02288 (NADH)
 21,914 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The histrochemistry of the adrenal glands was studied in four adult male marmosets (two Callithrix jacchus and two Callithrix penicillata). It was impossible to demonstrate any reactivity to UDPG-GT, ADH, alanyl aminopeptidase, leucine aminopeptidase, xilitol (NAD-dependent) dehydrogenase, beta-glucuronidase and aryl-sulfatase in these glands. Total phosphorylase was found in scattered cells of the glomerulosa and adjacent outer fasciculata of one C. penicillata. The dehydrogenases (LDH, G-6-PDH,6-PGDH, NADPH2-TR,ICDH,SDH,NADH2-TR, alpha-GPDH, beta-OHBDH) as well as the hydrolases (except alkaline phosphatase, ATPase, and acetylcholinesterase) showed a stonger reactivity in the cortical part. Some hydrolases (naphthol acetate esterase, acid phosphatase) and cytochrome oxidase were less reactive in the zona glomerulosa, where the dehydrogenases were more abundant. The outer fasciculata and the reticularis also showed a strong dehydrogenase reactivity.
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PMID:Histochemical studies on the adrenal glands of the marmosets (Callithrix jacchus and Callithrix penicillata). 0 44

Liver endoplasmic membrane contains two hemoproteins, cyt. P-450 and cyt. b5. Cytochrome P-450 catalyzes the hydroxylation of lipid-soluble compounds, while the cyt. b5 system is involved in desaturation of fatty acids. NAD(P)H and oxygen are essential components for both systems. Oxidation of ethanol to acetate in the liver, via alcohol and acetaldehyde dehydrogenases, leads to an elevated cellular NADH content. It has been proposed that oxidation of the cytosolic NADH occurs predominantly in the mitochondria via the substrate oxidation-reduction shuttle. In order to investigate the effects of elevated levels of cytosolic NADH on the state of the endoplasmic hemoprotein system, microsomes from a fatty human liver (post-ethanol intake) were isolated and studied. Microsomal cyt. b5 reductase was found to reoxidize cytoplasmic NADH directly and transfer the reducing equivalents readily to the microsomal oxidases. Addition of catalytic amounts of alcohol dehydrogenase, NAD, and ethanol to microsomes resulted in a rapid reduction of microsomal cyt. b5. These results are consistent with the proposal that the catalytic moiety of cyt. b5 reductase is exposed to the aqueous phase of the membrane and directly accepts reducing equivalents from the cytoplasm. Microsomes from fatty human liver showed an increased rate of cyt. b5 dependent desaturation of fatty acids. These findings suggest that ethanol metabolism may selectively affect the activity of one or the other microsomal hemoprotein. Thus, when the desaturase activity is low, drug metabolism by the cyt. P-450 pathway may predominate. Conversely, an increase in the desaturase level may lead to a decreased drug metabolism. This mechanism may underlie the clinical observations of drug intolerance reactions associated with alcohol intake.
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PMID:The role of microsomal cytochrome b5 in the metabolism of ethanol, drugs and the desaturation of fatty acids. 1 14

1. Initial-rate studies of the reduction of acetaldehyde by NADH, catalysed by yeast alcohol dehydrogenase, were performed at pH 4.9 and 9.9, in various buffers, at 25 degrees C. The results are discussed in terms of the mechanism previously proposed for the pH range 5.9-8.9 [Dickenson & Dickinson (1975) Biochem. J. 147, 303-311]. 2. Acetaldehyde forms a u.v.-absorbing complex with glycine. This was shown not to affect the results of kinetic experiments under the conditions used in this and earlier work. 3. The variation with pH of the dissociation constant for the enzyme-NADH complex, calculated from the initial-rate data, indicates that the enzyme possesses a group with pK7.1 in the free enzyme and pK8.7 in the complex. 4. The pH-dependences of the second-order rate constants for inactivation of the enzyme by diethyl pyrocarbonate were determined for the free enzymes (pK7.1), the enzyme-NAD+ complex (pK approx. 7.1) and the enzyme-NADH complex (pK approx. 8.4). The essential histidine residue may therefore be the group involved in formation and dissociation of the enzyme-NADH complex. 5. Estimates of the rate constant for reaction of acetaldehyde with the enzyme-NADH complex indicate that acetaldehyde may combine only when the essential histidine residue is protonated. The dissociation constants for butan-1-ol and propan-2-ol, calculated on the basis of earlier kinetic data, are, however, independent of pH. 6. The results obtained are discussed in relation to the role of the essential histidine residue in the mechanism of formation of binary and ternary complexes of the enzyme with its coenzymes and substrates.
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PMID:A study of the ionic properties of the essential histidine residue of yeast alcohol dehydrogenase in complexes of the enzyme with its coenzymes and substrates. 1 41

1. Inactivation of yeast alcohol dehydrogenase for diethyl pyrocarbonate indicates that one histidine residue per enzyme subunit is necessary for enzymic activity. The inactivated enzyme regains its activity over a period of days. 2. Enzyme modified by diethyl pyrocarbonate can form the binary enzyme - NADH complex with the same maximum NADH-binding capacity as that of native enzyme. Modified enzyme cannot form normal ternary complexes of the type enzyme - NADH - acetamide and enzyme - NAD+ - pyrazole, which are characteristic of native enzyme. 3. The rate constant for the reaction of enzyme with diethyl pyrocarbonate has been determined over the pH range 5.5--9. The histidine residue involved has approximately the same pKa as free histidine, but is 10-fold more reactive than free histidine.
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PMID:The role of an essential histidine residue of yeast alcohol dehydrogenase. 1 43

A rapid electrochemical measurement of blood ethanol is proposed. Alcohol is oxidized by NAD+ in the presence of alcohol dehydrogenase; and the NADH produced is aerobically oxidized by horseradish peroxidase. The rate of depletion of buffer-carried oxygen, which is directly proportional to the alcohol concentration in the sample, is amperometrically monitored with a membrane oxygen-sensing electrode. Only a 5-microliter sample of whole blood is required, with no deproteinization, incubation, extraction, or dilution. Results, obtained in less than 1 min, correlate well with those obtained by gas-chromatographic and spectrophotometric methods.
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PMID:Enzymatic determination of blood ethanol, with amperometric measurement of rate of oxygen depletion. 2 44

The pyruvate-to-ethanol pathway in Entamoeba histolytica is unusual when compared with most investigated organisms. Pyruvate decarboxylase (EC 4.1.1.1), a key enzyme for ethanol production, is not found. Pyruvate is converted into acetyl-CoA and CO2 by the enzyme pyruvate synthase (EC 1.2.7.1), which has been demonstrated previously in this parasitic amoeba. Acetyl-CoA is reduced to acetaldehyde and CoA by the enzyme aldehyde dehydrogenase (acylating) (EC 1.2.1.10) at an enzyme activity of 9 units per g of fresh cells with NADH as a reductant. Acetaldehyde is further reduced by either a previously identified NADP+-linked alcohol dehydrogenase or by a newly found NAD+-linked alcohol dehydrogenase at an enzyme activity of 136 units per g of fresh cells. Ethanol is identified as the product of soluble enzymes of amoeba acting on pyruvate or acetyl-CoA. This result is confirmed by radioactive isotopic, spectrophotometric and gas-chromatographic methods.
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PMID:Pyruvate-to-ethanol pathway in Entamoeba histolytica. 2 58

1. Kinetic relationships referring to multiple-turnover conditions have been derived for the slowest exponential transient appearing in two-substrate enzyme reactions proceeding by an ordered ternary-complex mechanism. The validity of these and previously derived theoretical relationships for this mechanism has been tested by application to the liver alcohol dehydrogenase reaction. 2. All essential features of the transient-state kinetics of alcohol oxidation by NAD+ in the liver alcohol dehydrogenase system can be qualitatively and quantitatively explained in view of the compulsory-order mechanism in the proposed scheme. There is no kinetic evidence for any half-of-the-sites reactivity of the enzyme. A consistent set of rate constants is reported for the enzymic oxidation of benzyl alcohol at pH 8.75. 3. Transient-state rate parameters for benzyl alcohol/benzaldehyde catalysis by liver alcohol dehydrogenase have been determined at different pH. The interpretation of such rate parameters is critically discussed with reference to their informative value for the purpose of determination of rate constants (k and k') for the process of ternary-complex interconversion in the proposed scheme. It is concluded that the apparent rate constant (k') for hydride transfer from benzyl alcohol to NAD+ is dependent on a proton dissociation step with a pKa of 6.4, whereas the rate constant (k) for hydride transfer from NADH to benzaldehyde exhibits no corresponding dependence on proton association. 4. The asymmetric pH dependence of the forward and reverse rate of ternary-complex interconversion during liver alcohol dehydrogenase catalysis appears to reflect an obligatory step of alcohol/alcoholate ion equilibration occurring at the ternary-complex level. It is suggested that the observed pKa 6.4 dependence of the transient rate of alcohol oxidation can be attributed to a coupled acid-base system involving minimally the enzyme-bound alcohol and the protein residues Ser-48 and His-51.
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PMID:Effect of pH on the process of ternary-complex interconversion in the liver-alcohol-dehydrogenase reaction. 2 59

1. Spectroscopic methods for protein and active-site determination with the same sample of immobilised horse liver alcohol dehydrogenase have been developed. 2. The influence of pH, active-site protection of the soluble enzyme and protein concentration on coupling of alcohol dehydrogenase with cyanogen-bromide-activated Sepharose has been investigated. In phosphate buffer (pH 8.0) products with over 90% active-site retention have been synthesized. The binary complex alcohol-dehydrogenase . NADH gives a preparation with the same active-site content but a lower apparent specific activity compared to the unprotected enzyme. Increase in protein concentration yields products with the same active-site content relative to bound protein but the apparent specific activity is decreased. 3. The great similarity in spectroscopic properties of soluble and immobilised enzyme, as well as of their ternary complexes, shows that no significant conformational change has taken place during immobilisation. 4. Exchange of the non-catalytic Zn2+ against Co2+ yields a hybrid Sepharose--Co2Zn2-alcohol-dehydrogenase with over 90% active-site retention during metal exchange. The absorption spectra of the soluble and immobilised hybrid are identical.
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PMID:Agarose-bound horse-liver alcohol dehydrogenase. Dependence of molecular properties and activity on coupling conditions. 3 33

Aldose reductase (alditol:NADP+ 1-oxidoreductase, EC 1.1.1.21) has been purified 1500-fold from porcine brain in a four-step procedure employing Blue-Sepharose 6B affinity chromatography. The purified enzyme was shown to be apparently homogeneous by polyacrylamide gel electrophoresis. The enzyme is a single chain polypeptide of molecular weight 40 000, pH optimum 5.0 K(app)(xylose) 4 mM; K(app)(NADPH) 3 microM. The relative substrate activities, activation with sulfate ion, and limited oxidative and NADH-related reductive activities confirm the classification of this enzyme as aldolase reductase. The activity of the reductase with p-nitrobenzaldehyde and 3-indolacetaldehyde and the similarity of its physical properties with the 'low Km' aldehyde reductase of porcine brain previously reported indicates that these enzymes may be identical.
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PMID:Affinity purification and properties of porcine brain aldose reductase. 3 51

The binding of NAD+, NADH, and ADP-ribose to horse liver alcohol dehydrogenase has been studied calorimetrically as a function of pH at 25 degrees C. The enthalpy of NADH binding is 0 +/- 0.5 kcal mol-1 in the pH range 6 to 8.6. The enthalpy of NAD+ binding, however, varies with pH in a sigmoidal fashion and is -4.0 kcal mol(NAD)-1 at pH 6.0 and +4.5 kcal mol(NAD)-1 at pH 8.6 with an apparent pKa of 7.6 +/- 0.2. The enthalpy of proton ionization of the group on the enzyme is calculated to be in the range 8.8 to 9.8 kcal mol(H+)-1. In conjunction with the available thermodynamic data on the ionization of zinc-bound water in model compounds, it is concluded that the group with a pKa of 9.8 in the free enzyme and 7.6 in the enzyme . NAD+ binary complex is, most likely, the zinc-bound water molecule. Our studies with zinc-free enzyme provide further evidence for this conclusion. Therefore, the processes involving a conformational change of the enzyme upon NAD+ binding and the suggested mechanism of subsequent quenching of the fluorescence of Trp-314 implicating the participation of an ionized tyrosine group must be re-evaluated in the light of this thermodynamic study.
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PMID:The enthalpy of protolysis of liver alcohol dehydrogenase upon binding nicotinamide adenine dinucleotide. 3 45


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