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Regina Pietruszko - One of the best experts on this subject based on the ideXlab platform.
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Betaine Aldehyde Dehydrogenase from rat liver mitochondrial matrix.
Chemico-Biological Interactions, 2001Co-Authors: Regina Pietruszko, Ming-kai ChernAbstract:An NAD-linked Aldehyde Dehydrogenase which in addition to aliphatic and aromatic Aldehydes, metabolizes aminoAldehydes and betaine Aldehyde, has been purified to homogeneity from male Sprague-Dawley rat liver mitochondria. The properties of the rat mitochondrial enzyme are similar to those of a rat liver cytoplasmic betaine Aldehyde dehydrognase and the human cytoplasmic E3 isozyme. The primary structure. of four tryptic peptides were also similar; only one difference in primary structure was observed. The close similarity of properties of the cytoplasmic with the mitochondrial form suggest that the cytoplasmic and mitochondrial betaine Aldehyde Dehydrogenase may be coded for by the same nuclear gene. Investigation of the mitochondrial form by isoelectric focusing resulted in visualization of multiple forms, different from those seen in the cytoplasm suggesting that the enzyme may be processed in the mitochondria.
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Evidence for mitochondrial localization of betaine Aldehyde Dehydrogenase in rat liver: purification, characterization, and comparison with human cytoplasmic E3 isozyme.
Biochemistry and cell biology = Biochimie et biologie cellulaire, 1999Co-Authors: Ming-kai Chern, Regina PietruszkoAbstract:Betaine Aldehyde Dehydrogenase has been purified to homogeneity from rat liver mitochondria. The properties of betaine Aldehyde Dehydrogenase were similar to those of human cytoplasmic E3 isozyme in substrate specificity and kinetic constants for substrates. The primary structure of four tryptic peptides was also similar; only two substitutions, at most, per peptide were observed. Thus, betaine Aldehyde Dehydrogenase is not a specific enzyme, as formerly believed; activity with betaine Aldehyde is a property of Aldehyde Dehydrogenase (EC 1.2.1.3), which has broad substrate specificity. Up to the present time the enzyme was thought to be cytoplasmic in mammals. This report establishes, for the first time, mitochondrial subcellular localization for Aldehyde Dehydrogenase, which dehydrogenates betaine Aldehyde, and its colocalization with choline Dehydrogenase. Betaine Aldehyde dehydrogenation is an important function in the metabolism of choline to betaine, a major osmolyte. Betaine is also important in mam...
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HALOENOL LACTONES AS INACTIVATORS AND SUBSTRATES OF Aldehyde Dehydrogenase
Journal of protein chemistry, 1996Co-Authors: Neeta Mukerjee, Marek Dryjanski, Wei Dai, John A. Katzenellenbogen, Regina PietruszkoAbstract:Human Aldehyde Dehydrogenase (EC 1.2.1.3) isozymes E1 and E2 were irreversibly inactivated by stoichiometric concentrations of the haloenol lactones 3-isopropyl-6(E)-bromomethylene tetrahydro-pyran-2-one and 3-phenyl-6(E)-bromomethylene tetrahydro-pyran-2-one. No inactivation occurred with the corresponding nonhalogenated enol lactones. Both the Dehydrogenase and esterase activities were abolished. Activity was not regained on dialysis or treatment with 2-mercaptoethanol. The inactivation was subject to substrate protection: NAD afforded protection which increased in the presence of the Aldehyde-substrate competitive inhibitor chloral. Saturation kinetics gave positivey-axis intercepts, allowing the determination of binding constants. Inactivation stiochiometry determined with14C-labeled 3-(1-naphthyl)-6(E)-iodomethylene tetrahydropyran-2-one was found to correspond to the active-site number. The nonhalogenated lactone, 3-(1-naphthyl)-6(E)-methylene tetrahydropyran-1-one was shown to be a substrate for Aldehyde Dehydrogenase via its esterase function. Inactivation and enzymatic hydrolysis occurred within a similar time frame. Opening of the lactone ring to form enzyme-acyl intermediate with active site cysteine appears to be a necessary prerequisite to inactivation, since halogen in the lactone ring is nonreactive. Thus, the inactivation of Aldehyde Dehydrogenase by haloenol lactones is mechanism-based. Inactivation by haloenol lactones occurs in a manner analogous to that of chymotrypsin with which Aldehyde Dehydrogenase shares esterase activity and binding of haloenol lactones at the active site.
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Human Aldehyde Dehydrogenase E3 isozyme is a betaine Aldehyde Dehydrogenase.
Biochemical and biophysical research communications, 1995Co-Authors: Ming-kai Chern, Regina PietruszkoAbstract:The E3 isozyme of human Aldehyde Dehydrogenase (EC 1.2.1.3), with broad substrate specificity, which also catalyzes dehydrogenation of 4-aminobutyrAldehyde, was purified and sequenced recently (1,3). It has been shown during this investigation to have betaine Aldehyde Dehydrogenase activity. Betaine Aldehyde and 4-aminobutyrAldehyde activities copurified on six chromatographic columns. Molecular properties of the homogeneous product were identical with those of E3 isozyme. Activity with betaine Aldehyde was considerably higher than that with 4-aminobutyrAldehyde, the best known substrate. Thus, human E3 isozyme and betaine Aldehyde Dehydrogenase (EC 1.2.1.8) are the same enzyme.
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METABOLIC ROLE OF Aldehyde Dehydrogenase
Advances in experimental medicine and biology, 1993Co-Authors: Wojciech Ambroziak, Regina PietruszkoAbstract:Aldehyde Dehydrogenase (EC 1.2.1.3), an enzyme with a broad substrate specificity and low Km values for short chain aliphatic Aldehydes utilizes NAD as coenzyme, is universally distributed in mammalian livers and also at lower concentrations in other organs. The enzyme is a homotetramer of MW of ca. 220,000 (see review by Pietruszko, 1989). Because of its broad substrate specificity, it is frequently considered to be an enzyme of detoxication which functions in the organisms in oxidation of toxic Aldehydes ingested in foodstuffs (see review by Jakoby and Ziegler, 1990). Metabolism of ethanol derived acetAldehyde, which is known to be catalyzed by this enzyme (Parrilla et al., 1974) is an example of detoxication role of Aldehyde Dehydrogenase. In the human liver the enzyme occurs as three known isozymes, El, E2 and E3; other isozymes not yet identified may exist.
Ming-kai Chern - One of the best experts on this subject based on the ideXlab platform.
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Betaine Aldehyde Dehydrogenase from rat liver mitochondrial matrix.
Chemico-Biological Interactions, 2001Co-Authors: Regina Pietruszko, Ming-kai ChernAbstract:An NAD-linked Aldehyde Dehydrogenase which in addition to aliphatic and aromatic Aldehydes, metabolizes aminoAldehydes and betaine Aldehyde, has been purified to homogeneity from male Sprague-Dawley rat liver mitochondria. The properties of the rat mitochondrial enzyme are similar to those of a rat liver cytoplasmic betaine Aldehyde dehydrognase and the human cytoplasmic E3 isozyme. The primary structure. of four tryptic peptides were also similar; only one difference in primary structure was observed. The close similarity of properties of the cytoplasmic with the mitochondrial form suggest that the cytoplasmic and mitochondrial betaine Aldehyde Dehydrogenase may be coded for by the same nuclear gene. Investigation of the mitochondrial form by isoelectric focusing resulted in visualization of multiple forms, different from those seen in the cytoplasm suggesting that the enzyme may be processed in the mitochondria.
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Evidence for mitochondrial localization of betaine Aldehyde Dehydrogenase in rat liver: purification, characterization, and comparison with human cytoplasmic E3 isozyme.
Biochemistry and cell biology = Biochimie et biologie cellulaire, 1999Co-Authors: Ming-kai Chern, Regina PietruszkoAbstract:Betaine Aldehyde Dehydrogenase has been purified to homogeneity from rat liver mitochondria. The properties of betaine Aldehyde Dehydrogenase were similar to those of human cytoplasmic E3 isozyme in substrate specificity and kinetic constants for substrates. The primary structure of four tryptic peptides was also similar; only two substitutions, at most, per peptide were observed. Thus, betaine Aldehyde Dehydrogenase is not a specific enzyme, as formerly believed; activity with betaine Aldehyde is a property of Aldehyde Dehydrogenase (EC 1.2.1.3), which has broad substrate specificity. Up to the present time the enzyme was thought to be cytoplasmic in mammals. This report establishes, for the first time, mitochondrial subcellular localization for Aldehyde Dehydrogenase, which dehydrogenates betaine Aldehyde, and its colocalization with choline Dehydrogenase. Betaine Aldehyde dehydrogenation is an important function in the metabolism of choline to betaine, a major osmolyte. Betaine is also important in mam...
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Human Aldehyde Dehydrogenase E3 isozyme is a betaine Aldehyde Dehydrogenase.
Biochemical and biophysical research communications, 1995Co-Authors: Ming-kai Chern, Regina PietruszkoAbstract:The E3 isozyme of human Aldehyde Dehydrogenase (EC 1.2.1.3), with broad substrate specificity, which also catalyzes dehydrogenation of 4-aminobutyrAldehyde, was purified and sequenced recently (1,3). It has been shown during this investigation to have betaine Aldehyde Dehydrogenase activity. Betaine Aldehyde and 4-aminobutyrAldehyde activities copurified on six chromatographic columns. Molecular properties of the homogeneous product were identical with those of E3 isozyme. Activity with betaine Aldehyde was considerably higher than that with 4-aminobutyrAldehyde, the best known substrate. Thus, human E3 isozyme and betaine Aldehyde Dehydrogenase (EC 1.2.1.8) are the same enzyme.
Hans Jörnvall - One of the best experts on this subject based on the ideXlab platform.
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11-Hydroxythromboxane B2 Dehydrogenase is identical to cytosolic Aldehyde Dehydrogenase.
FEBS Letters, 1994Co-Authors: Pär Westlund, Ann Catrin Fylling, Ella Cederlund, Hans JörnvallAbstract:11 -Hydroxythromboxane B2 Dehydrogenase purified from porcine kidney has been identified as cytosolic Aldehyde Dehydrogenase (EC 1.2.1.3). This identification is based on protein characteristics, sequence analysis of one proteolytic digest, blocked N-terminus, subunit molecular mass of 55 kDa, and enzymatic activities. The sequence difference with the human enzyme is 7.5% in the fragments analyzed (29 exchanges of 388 positions, corresponding to the expected species variability for cytosolic Aldehyde Dehydrogenase The substrate thromboxane B2 contains a hemiacetal in its ring structure, but the reaction most likely proceeds via the Aldehyde form of the substrate. This finding is in agreement with the proposed metabolism of 4-hydroxycyclophosphamide and highlights the possibility that molecules containing a hemiacetal structure can function as substrates for Aldehyde Dehydrogenase.
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Structural features of stomach Aldehyde Dehydrogenase distinguish dimeric Aldehyde Dehydrogenase as a ‘variable’ enzyme ‘Variable’ and ‘constant’ enzymes within the alcohol and Aldehyde Dehydrogenase families
FEBS letters, 1991Co-Authors: Shih-jiun Yin, Nikolaos Vagelopoulos, Sung-ling Wang, Hans JörnvallAbstract:Stomach Aldehyde Dehydrogenase was structurally evaluated by analysis of peptide fragments of the human enzyme and comparisons with corresponding parts from other characterized Aldehyde Dehydrogenases. The results establish a large part of the structure, confirming that the stomach enzyme is identical to the inducible or tumor-derived dimeric Aldehyde Dehydrogenase. In addition, species variations between identical sets of different Aldehyde and alcohol Dehydrogenases reveal that stomach Aldehyde Dehydrogenase exhibits a fairly rapid rate of evolutionary changes, similar to that for the likewise ‘variable’ classical alcohol Dehydrogenase, sorbitol Dehydrogenase, and cytosolic Aldehyde Dehydrogenase but in contrast to the ‘constant’ class III alcohol Dehydrogenase and mitochondrial Aldehyde Dehydrogenase. This establishes that rates of divergence in the Aldehyde and alcohol Dehydrogenases are unrelated to subunit size or quaternary structure, highlights the unique nature of class III alcohol Dehydrogenase, and positions the stomach Aldehyde Dehydrogenase in a group with more ordinary features.
Christine Beedham - One of the best experts on this subject based on the ideXlab platform.
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Metabolism of isovanillin by Aldehyde oxidase, xanthine oxidase, Aldehyde Dehydrogenase and liver slices.
Pharmacology, 2004Co-Authors: Georgios I. Panoutsopoulos, Christine BeedhamAbstract:Aromatic Aldehydes are good substrates of Aldehyde Dehydrogenase activity but are relatively poor substrates of Aldehyde oxidase and xanthine oxidase. However, the oxidation of xenobiotic-derived aromatic Aldehydes by the latter enzymes has not been studied to any great extent. The present investigation compares the relative contribution of Aldehyde Dehydrogenase, Aldehyde oxidase and xanthine oxidase activities in the oxidation of isovanillin in separate preparations and also in freshly prepared and cryopreserved liver slices. The oxidation of isovanillin was also examined in the presence of specific inhibitors of each oxidizing enzyme. Minimal transformation of isovanillin to isovanillic acid was observed in partially purified Aldehyde oxidase, which is thought to be due to residual xanthine oxidase activity. Isovanillin was rapidly metabolized to isovanillic acid by high amounts of purified xanthine oxidase, but only low amounts are present in guinea pig liver fraction. Thus the contribution of xanthine oxidase to isovanillin oxidation in guinea pig is very low. In contrast, isovanillin was rapidly catalyzed to isovanillic acid by guinea pig liver Aldehyde Dehydrogenase activity. The inhibitor studies revealed that isovanillin was predominantly metabolized by Aldehyde Dehydrogenase activity. The oxidation of xenobiotic-derived aromatic Aldehydes with freshly prepared or cryopreserved liver slices has not been previously reported. In freshly prepared liver slices, isovanillin was rapidly converted to isovanillic acid, whereas the conversion was very slow in cryopreserved liver slices due to low Aldehyde Dehydrogenase activity. The formation of isovanillic acid was not altered by allopurinol, but considerably inhibited by disulfiram. It is therefore concluded that isovanillin is predominantly metabolized by Aldehyde Dehydrogenase activity, with minimal contribution from either Aldehyde oxidase or xanthine oxidase.
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Contribution of Aldehyde Oxidase, Xanthine Oxidase, and Aldehyde Dehydrogenase on the Oxidation of Aromatic Aldehydes
Chemical research in toxicology, 2004Co-Authors: Georgios I. Panoutsopoulos, Demetrios Kouretas, Christine BeedhamAbstract:Aliphatic Aldehydes have a high affinity toward Aldehyde Dehydrogenase activity but are relatively poor substrates of Aldehyde oxidase and xanthine oxidase. In addition, the oxidation of xenobiotic-derived aromatic Aldehydes by the latter enzymes has not been studied to any great extent. The present investigation compares the relative contribution of Aldehyde Dehydrogenase, Aldehyde oxidase, and xanthine oxidase activities in the oxidation of substituted benzAldehydes in separate preparations. The incubation of vanillin, isovanillin, and protocatechuic Aldehyde with either guinea pig liver Aldehyde oxidase, bovine milk xanthine oxidase, or guinea pig liver Aldehyde Dehydrogenase demonstrated that the three Aldehyde oxidizing enzymes had a complementary substrate specificity. Incubations were also performed with specific inhibitors of each enzyme (isovanillin for Aldehyde oxidase, allopurinol for xanthine oxidase, and disulfiram for Aldehyde Dehydrogenase) to determine the relative contribution of each enzyme in the oxidation of these Aldehydes. Under these conditions, vanillin was rapidly oxidized by Aldehyde oxidase, isovanillin was predominantly metabolized by Aldehyde Dehydrogenase activity, and protocatechuic Aldehyde was slowly oxidized, possibly by all three enzymes. Thus, Aldehyde oxidase activity may be a significant factor in the oxidation of aromatic Aldehydes generated from amines and alkyl benzenes during drug metabolism. In addition, this enzyme may also have a role in the catabolism of biogenic amines such as dopamine and noradrenaline where 3-methoxyphenylacetic acids are major metabolites.
D. Sasse - One of the best experts on this subject based on the ideXlab platform.
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Spatial distribution of human liver Aldehyde Dehydrogenase isoenzymes.
Histochemistry and cell biology, 1999Co-Authors: I. P. Maly, Valérie Crotet, D. SasseAbstract:To elucidate the pattern of lesions in the liver parenchyma after ethanol ingestion, the quantitative distribution profiles of both the cytosolic and the mitochondrial Aldehyde Dehydrogenase isoenzyme activities were determined by the use of ultrathin-layer electrophoresis. It was found that in human liver parenchyma, both isoforms of Aldehyde Dehydrogenase are almost homogeneously represented in the liver acinus. These quantitative data are supported by the results of an improved histochemical technique. Moreover, sex differences were not detected either in activity or in the distribution pattern. Consequently, it can be assumed that it is not the activity of total Aldehyde Dehydrogenase or its isoforms which is responsible for the higher susceptibility of the perivenous zone to alcohol-dependent damage.
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The intramucosal distribution of gastric alcohol Dehydrogenase and Aldehyde Dehydrogenase activity in rats.
Histochemistry, 1992Co-Authors: I. P. Maly, M. Arnold, K. Krieger, M. Zalewska, D. SasseAbstract:Using qualitative and microquantitative histochemical techniques, alcohol Dehydrogenase and Aldehyde Dehydrogenase activity was studied in the gastric mucosa of male and female rats. Alcohol Dehydrogenase was demonstrated by staining reactions with maximum activity in surface and neck cells and with clearly weaker activity also in parietal cells. Aldehyde Dehydrogenase could be detected in surface and neck cells, and also to a comparable degree in the parietal cells. Quantitative analyses of microdissected samples yielded high values for alcohol Dehydrogenase activity exclusively in the superficial part of the gastric mucosa, whereas low-K m Aldehyde Dehydrogenase activity showed a decreasing gradient from the surface to the deeper parts of the mucosa. Sex differences could not be confirmed.
