scholarly journals Mechanism of inactivation of sheep liver cytoplasmic aldehyde dehydrogenase by disulfiram

1983 ◽  
Vol 213 (2) ◽  
pp. 551-554 ◽  
Author(s):  
T M Kitson
Keyword(s):  
Catalytic Activity ◽  
Aldehyde Dehydrogenase ◽  
Enzymic Activity ◽  
Sheep Liver ◽  
Oxidation Reduction

Stoicheiometric amounts of [14C]disulfiram react rapidly with sheep liver cytoplasmic aldehyde dehydrogenase to give loss of catalytic activity and incorporation of the expected amount of radioactivity. In a subsequent slower reaction the label is lost from the enzyme without re-emergence of enzymic activity. The results imply that in vivo disulfiram may act as an oxidation-reduction catalyst for the inactivation of aldehyde dehydrogenase.

scholarly journals Reaction between sheep liver mitochondrial aldehyde dehydrogenase and various thiol-modifying reagents

1989 ◽  
Vol 261 (1) ◽  
pp. 281-284 ◽  
Author(s):  
K M Loomes ◽  
T M Kitson
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Related Compound ◽  
Physiological Responses ◽  
Enzymic Activity ◽  
Cysteine Residues ◽  
Mitochondrial Enzyme ◽  
Step Process ◽  
Cytoplasmic Enzyme ◽  
Sheep Liver

Sheep liver mitochondrial aldehyde dehydrogenase reacts with 2,2′-dithiodipyridine and 4,4′-dithiodipyridine in a two-step process: an initial rapid labelling reaction is followed by slow displacement of the thiopyridone moiety. With the 4,4′-isomer the first step results in an activated form of the enzyme, which then loses activity simultaneously with loss of the label (as has been shown to occur with the cytoplasmic enzyme). With 2,2′-dithiodipyridine, however, neither of the two steps of the reaction has any effect on the enzymic activity, showing that the mitochondrial enzyme possesses two cysteine residues that must be more accessible or reactive (to this reagent at least) than the postulated catalytically essential residue. The symmetrical reagent 5,5′-dithiobis-(1-methyltetrazole) activates mitochondrial aldehyde dehydrogenase approximately 4-fold, whereas the smaller related compound methyl l-methyltetrazol-5-yl disulphide is a potent inactivator. These results support the involvement of mixed methyl disulphides in causing unpleasant physiological responses to ethanol after the ingestion of certain antibiotics.

scholarly journals Steady-state and pre-steady kinetic studies on mitochondrial sheep liver aldehyde dehydrogenase. A comparison with the cytoplasmic enzyme

1978 ◽  
Vol 171 (3) ◽  
pp. 527-531 ◽  
Author(s):  
A K H MacGibbon ◽  
L F Blackwell ◽  
P D Buckley
Keyword(s):  
Steady State ◽  
Aldehyde Dehydrogenase ◽  
Kinetic Studies ◽  
Kinetic Properties ◽  
Protein Fluorescence ◽  
Sheep Liver ◽  
Steady State Kinetic ◽  
Wide Range ◽  
Liver Aldehyde Dehydrogenase

Kinetic studies were carried out on mitochondrial aldehyde dehydrogenase (EC 1.2.1.3) isolated from sheep liver. Steady-state studies over a wide range of acetaldehyde concentrations gave a non-linear double-reciprocal plot. The dissociation of NADH from the enzyme was a biphasic process with decay constants 0.6s-1 and 0.09s-1. Pre-steady-state kinetic data with propionaldehyde as substrate could be fitted by using the same burst rate constant (12 +/- 3s-1) over a wide range of propionaldehyde concentrations. The quenching of protein fluorescence on the binding of NAD+ to the enzyme was used to estimate apparent rate constants for binding (2 × 10(4) litre.mol-1.s-1) and dissociation (4s-1). The kinetic properties of the mitochondrial enzyme, compared with those reported for the cytoplasmic aldehyde dehydrogenase from sheep liver, show significant differences, which may be important in the oxidation of aldehydes in vivo.

scholarly journals Some properties of aldehyde dehydrogenase from sheep liver mitochondria

1977 ◽  
Vol 163 (2) ◽  
pp. 261-267 ◽  
Author(s):  
G J Hart ◽  
F M Dickinson
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Liver Mitochondria ◽  
Enzymic Activity ◽  
Sedimentation Equilibrium ◽  
Thiol Groups ◽  
Control Value ◽  
Sheep Liver ◽  
Spectrophotometric Titrations ◽  
A Subunit ◽  
Subunit Size

Aldehyde dehydrogenase from sheep liver mitochondria was purified to homogeneity as judged by electrophoresis on polyacrylamide gels, and by sedimentation-equilibrium experiments in the analytical ultracentrifuge. The enzyme has a molecular weight of 198000 and a subunit size of 48000, indicating that the molecule is a tetramer. Fluorescence and spectrophotometric titrations indicate that each subunit can bind 1 molecule of NADH. Enzymic activity is completely blocked by reaction of 4mol of 5,5′-dithiobis-(2-nitrobenzoate)/mol of enzyme. Excess of disulfiram or iodoacetamide decreases activity to only 50% of the control value, and only two thiol groups per molecule are apparently modified by these reagents.

scholarly journals Oscillatory Behaviour of Ni Supported on ZrO2 in the Catalytic Partial Oxidation of Methane as Determined by Activation Procedure

Materials ◽  
2021 ◽  
Vol 14 (10) ◽  
pp. 2495
Author(s):  
Daniela Pietrogiacomi ◽  
Maria Cristina Campa ◽  
Ida Pettiti ◽  
Simonetta Tuti ◽  
Giulia Luccisano ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Partial Oxidation ◽  
Active Sites ◽  
Direct Reduction ◽  
Partial Oxidation Of Methane ◽  
Catalytic Partial Oxidation ◽  
Oxidation Of Methane ◽  
Short Contact Time ◽  
Oxidation Reduction ◽  
Ni Species

Ni/ZrO2 catalysts, active and selective for the catalytic partial oxidation of methane to syngas (CH4-CPO), were prepared by the dry impregnation of zirconium oxyhydroxide (Zhy) or monoclinic ZrO2 (Zm), calcination at 1173 K and activation by different procedures: oxidation-reduction (ox-red) or direct reduction (red). The characterization included XRD, FESEM, in situ FTIR and Raman spectroscopies, TPR, and specific surface area measurements. Catalytic activity experiments were carried out in a flow apparatus with a mixture of CH4:O2 = 2:1 in a short contact time. Compared to Zm, Zhy favoured the formation of smaller NiO particles, implying a higher number of Ni sites strongly interacting with the support. In all the activated Ni/ZrO2 catalysts, the Ni–ZrO2 interaction was strong enough to limit Ni aggregation during the catalytic runs. The catalytic activity depended on the activation procedures; the ox-red treatment yielded very active and stable catalysts, whereas the red treatment yielded catalysts with oscillating activity, ascribed to the formation of Niδ+ carbide-like species. The results suggested that Ni dispersion was not the main factor affecting the activity, and that active sites for CH4-CPO could be Ni species at the boundary of the metal particles in a specific configuration and nuclearity.

scholarly journals Effect of Posttranslational Modifications on the Structure and Activity of FTO Demethylase

2021 ◽  
Vol 22 (9) ◽  
pp. 4512
Author(s):  
Michał Marcinkowski ◽  
Tomaš Pilžys ◽  
Damian Garbicz ◽  
Jan Piwowarski ◽  
Damian Mielecki ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Size Exclusion Chromatography ◽  
Posttranslational Modifications ◽  
Size Exclusion ◽  
Saxs Data ◽  
Wide Range ◽  
Exclusion Chromatography ◽  
Demethylase Activity ◽  
Structure And Activity

The FTO protein is involved in a wide range of physiological processes, including adipogenesis and osteogenesis. This two-domain protein belongs to the AlkB family of 2-oxoglutarate (2-OG)- and Fe(II)-dependent dioxygenases, displaying N6-methyladenosine (N6-meA) demethylase activity. The aim of the study was to characterize the relationships between the structure and activity of FTO. The effect of cofactors (Fe2+/Mn2+ and 2-OG), Ca2+ that do not bind at the catalytic site, and protein concentration on FTO properties expressed in either E. coli (ECFTO) or baculovirus (BESFTO) system were determined using biophysical methods (DSF, MST, SAXS) and biochemical techniques (size-exclusion chromatography, enzymatic assay). We found that BESFTO carries three phosphoserines (S184, S256, S260), while there were no such modifications in ECFTO. The S256D mutation mimicking the S256 phosphorylation moderately decreased FTO catalytic activity. In the presence of Ca2+, a slight stabilization of the FTO structure was observed, accompanied by a decrease in catalytic activity. Size exclusion chromatography and MST data confirmed the ability of FTO from both expression systems to form homodimers. The MST-determined dissociation constant of the FTO homodimer was consistent with their in vivo formation in human cells. Finally, a low-resolution structure of the FTO homodimer was built based on SAXS data.

scholarly journals Catalytic Activity of Oxidation-Reduction Pre-Treated Ni3Al for Methane Steam Reforming

2010 ◽  
Vol 89-91 ◽  
pp. 645-650 ◽  
Author(s):  
Ya Xu ◽  
Dong Hyun Chun ◽  
Jun Hyuk Jang ◽  
Masahiko Demura ◽  
Dang Moon Wee ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Steam Reforming ◽  
Active Surface ◽  
Methane Steam Reforming ◽  
Reduction Treatment ◽  
Highly Active ◽  
Methane Steam ◽  
Oxidation Reduction ◽  
Pre Treatment ◽  
Oxidation In Air

The catalytic activity of oxidation-reduction pre-treated Ni3Al powder for methane steam reforming was examined. The oxidation-reduction pre-treatment consisted of two steps: oxidation in air at various temperatures from 973 to 1373 K, and then followed by reduction in H2 at 873 K. It was found that the oxidation-reduction treatments significantly reduced the onset temperature of activity, i.e., improved the activity of Ni3Al powder at low temperatures. The characterization of Ni3Al surface showed that an outer surface layer of fine NiO particles were formed on the surface of Ni3Al after oxidation. These NiO particles were reduced to metallic Ni by the subsequent reduction treatment, resulting in the high activity for methane steam reforming. These results indicate that the Ni3Al can form highly active surface structure with oxidation-reduction treatment, having excellent heat resistance.

scholarly journals Small–molecule therapeutics for the treatment of glycolipid lysosomal storage disorders

2003 ◽  
Vol 358 (1433) ◽  
pp. 927-945 ◽  
Author(s):  
Terry D. Butters ◽  
Howard R. Mellor ◽  
Keishi Narita ◽  
Raymond A. Dwek ◽  
Frances M. Platt
Keyword(s):  
Catalytic Activity ◽  
Lysosomal Storage Disorders ◽  
Substrate Reduction Therapy ◽  
Lysosomal Storage ◽  
Substrate Reduction ◽  
Treatment Demand ◽  
Small Molecule Therapeutics ◽  
Storage Disorders

Glycosphingolipid (GSL) lysosomal storage disorders are a small but challenging group of human diseases to treat. Although these disorders appear to be monogenic in origin, where the catalytic activity of enzymes in GSL catabolism is impaired, the clinical presentation and severity of disease are heterogeneous. Present attitudes to treatment demand individual therapeutics designed to match the specific disease–related gene defect; this is an acceptable approach for those diseases with high frequency, but it lacks viability for extremely rare conditions. An alternative therapeutic approach termed ‘substrate deprivation’ or ‘substrate reduction therapy’ (SRT) aims to balance cellular GSL biosynthesis with the impairment in catalytic activity seen in lysosomal storage disorders. The development of N–alkylated iminosugars that have inhibitory activity against the first enzyme in the pathway for glucosylating sphingolipid in eukaryotic cells, ceramide–specific glucosyltransferase, offers a generic therapeutic for the treatment of all glucosphingolipidoses. The successful use of N–alkylated iminosugars to establish SRT as an alternative therapeutic strategy has been demonstrated in in vitro , in vivo and in clinical trials for type 1 Gaucher disease. The implications of these studies and the prospects of improvement to the design of iminosugar compounds for treating Gaucher and other GSL lysosomal storage disorders will be discussed.

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