Showing papers on "Aldehyde dehydrogenase published in 1975"
TL;DR: The properties and distribution of the NAD-linked unspecific aldehyde dehydrogenase activity has been studied in isolated cytoplasmic, mitochondrial and microsomal fractions of rat liver.
198 citations
TL;DR: The results indicate that the OCT plasmid codes for inducible alkane-hydroxylating and primary alcohol-dehydrogenating activities and that the chromosome codes for constitutive oxidizing activities for primary alcohols, aliphatic aldehydes, and fatty acids.
Abstract: We have studied the appearance of whole-cell oxidizing activity for n-alkanes and their oxidation products in strains of Pseudomonas putida carrying the OCT plasmid Our results indicate that the OCT plasmid codes for inducible alkane-hydroxylating and primary alcohol-dehydrogenating activities and that the chromosome codes for constitutive oxidizing activities for primary alcohols, aliphatic aldehydes, and fatty acids Mutant isolation confirms the presence of an alcohol dehydrogenase locus on the OCT plasmid and indicated the presence of multiple alcohol and aldehyde dehydrogenase loci on the P putida chromosome Induction tests with various compounds indicate that inducer recognition has specificity for chain length and can be affected by the degree of oxidation of the carbon chain Some inducers are neither growth nor respiration substrates Growth tests with and without a gratuitous inducer indicate that undecane is not a growth substrate because it does not induce alkane hydroxylase activity Using a growth test for determining induction of the plasmid alcohol dehydrogenase it is possible to show that heptane induces this activity in hydroxylase-negative mutants This suggests that unoxidized alkane molecules are the physiological inducers of both plasmid activities
159 citations
TL;DR: It is concluded that the higher activities in the AA strain are due mainly to those aldehyde dehydrogenases of mitochondrial and microsomal fractions, which have K m -values for aldehydes in the millimolar range.
100 citations
TL;DR: It was shown that the mixed disulphide, Et2N-CS-SS- CH2-CH2-Ch2OH, strongly inhibits aldehyde dehydrogenase and the inhibitory effect of diethyldithiocarbamate in vitro is due mainly to contamination by disulfiram.
Abstract: 1. The effect of disulfiram on the activity of the cytoplasmic and mitochondrial aldehyde dehydrogenases of sheep liver was studied. 2. Disulfiram causes an immediate inhibition of the enzyme reaction. The effect on the cytoplasmic enzyme is much greater than on the mitochondrial enzyme. 3. In both cases, the initial partial inhibition is followed by a gradual irreversible loss of activity. 4. The pH-rate profile of the inactivation of the mitochondrial enzyme by disulfiram and the pH-dependence of the maximum velocity of the enzyme-catalysed reaction are both consistent with the involvement of a thiol group. 5. Excess of 2-mercaptoethanol or GSH abolishes the effect of disulfiram. However, equimolar amounts of either of these reagents and disulfiram cause an effect greater than does disulfiram alone. It was shown that the mixed disulphide, Et2N-CS-SS-CH2-CH2OH, strongly inhibits aldehyde dehydrogenase. 6. The inhibitory effect of diethyldithiocarbamate in vitro is due mainly to contamination by disulfiram.
99 citations
Journal Article•
TL;DR: 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-methylcycloph phosphamide in an unfractionated incubation mixture with liver soluble enzymes did not cause reduced nicotinamidine din nucleotide production.
Abstract: 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.
Activated 4-methylcyclophosphamide was deactivated by liver cytosol to the same extent as phosphoramide mustard (dose reduction factors, 2.2 and 2.7, respectively); that for liver cytosol and activated cyclophosphamide was 49.1.
It was concluded that the selective action of cyclophosphamide when compared to other nitrogen mustards is largely dependent on the balance between the enzymatic production of nontoxic metabolites (principally carboxyphosphamide) and chemical decomposition of aldophosphamide to the ultimate alkylating agent (phosphoramide mustard).
93 citations
TL;DR: Evidence supporting the existence of three aldehyde dehydrogenases, betaine aldechemical dehydrogenase, ALDH-I and AL DH-II, in rat liver has been confirmed.
84 citations
TL;DR: Measurement of in vivo alcohol disappearance rate indicates the old male group is different from the other groups because of a slower rate of alcohol metabolism, further evidence that hepatic ADH and ALDH activities are not rate limiting in alcohol metabolism.
Abstract: Alcohol-induced sleep time was measured subsequent to the intraperitoneal injection of a 3.5 g x kg-1 dose. The old male group had a sleep time approximately 4 times that of the young male group and approximately twice that of the old female group. Blood alcohol concentrations at time of awakening were nearly identical in all groups, indicating the difference in sleep time is not due to an altered CNS sensitivity. Measurement of in vivo alcohol disappearance rate indicates the old male group is different from the other groups because of a slower rate of alcohol metabolism. Although changes in hepatic alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities were seen, the changes do not explain the observed decrease in alcohol metabolism observed in the old male group. These data provide further evidence that hepatic ADH and ALDH activities are not rate limiting in alcohol metabolism.
83 citations
TL;DR: It is concluded that cytosolic aldehyde dehydrogenase plays only a minor role in the oxidation of acetaldehyde during ethanol metabolism.
Abstract: The activity of a high-Km aldehyde dehydrogenase in the liver cytosol was increased by phenobarbital induction. No corresponding increase in the oxidation rate of acetaldehyde in vivo was found, and it is concluded that cytosolic aldehyde dehydrogenase plays only a minor role in the oxidation of acetaldehyde during ethanol metabolism.
78 citations
TL;DR: Human liver aldehyde dehydrogenase has been found to be capable of hydrolyzing p-nitrophenyl esters, and kinetics of activation of ester hydrolysis were consistent with random addition of pyridine nucleotide modifier and ester substrate to this enzyme.
73 citations
TL;DR: The subcellular distribution of human liver aldehyde dehydrogenases has been studied and the different types have been separated by ion exchange chromatography, finding evidence for slight high-K m activity in mitochondria and cytoplasmic fraction.
65 citations
TL;DR: Profound reduction of mitochondrial low- K m aldehyde dehydrogenase activity and high blood acetaldehyde were observed, especially in the ANA rats, which suggests a possible connection between the low activity of this enzyme and the increased acetaldehyde level.
TL;DR: Properties of the phenobarbital induced cytoplasmic aldehyde dehydrogenase (EC 1.2.1.3) have been studied in rat liver and the enzyme was inhibited by submicromolar concentrations of disulfiram and Estrone, deoxycorticosterone, progesterone and diethylstilbestrol affected the enzyme activity.
TL;DR: Comparisons between kinetic constants associated with the dehydrogenase and esterase activities of this enzyme suggested that most of the dehydration reaction flux proceeds via formation of an initial binary NAD+-enzyme complex over a wide range of substrate and coenzyme concentrations.
TL;DR: The results demonstrate that an unknown dietary factor affects the activity of liver aldehyde dehydrogenase, especially that of the low-K m enzyme, which may be associated with the magnitude of the shift in the mitochondrial redox state during ethanol oxidation.
TL;DR: Summary Active Enzyme Centrifugation experiments show that aldehyde dehydrogenase activity in E. Coli is associated with soluble particles the sedimentation coefficients of which are centered around 40 S.
TL;DR: Results indicate that in the rat the 3 enzymes are not localized with tyrosine hydroxylase, in the dopaminergic nerve terminals of the striatum, and that in this species the amine is not necessarily taken up by the nerve terminals prior to catabolism.
Abstract: —
A number of enzymes have been measured in the striatum of rats in which the dopamine-containing nerve terminals had been unilaterally destroyed by means of unipolar electrolytic lesions of the medial fore-brain bundle. Fourteen and 28 days after such lesions the tyrosine hydroxylase activity of the striatum was reduced to immeasurably low values, but neither aldehyde dehydrogenase, aldehyde reductase, nor acetylcholine esterase was affected when compared with the striatum from the intact side of the same rat or with those from control rats. These results indicate that in the rat the 3 enzymes are not localized with tyrosine hydroxylase, in the dopaminergic nerve terminals of the striatum. This conclusion is supported by a study of the subcellular localization of aldehyde dehydrogenase in rat brain. This enzyme is distributed between the cytosol and the particulate fraction of brain homogenates separated by centrifugal techniques. with no exceptionally high concentration of the enzyme in the synaptosomal fraction. Because neither of the enzymes of post-deaminative catabolism of dopamine is concentrated in the dopaminergic nerve terminals of the striatum of the rat, it is proposed that in this species the amine is not necessarily taken up by the nerve terminals prior to catabolism.
01 Jan 1975
TL;DR: The properties of this ester enzyme activity and their implications with respect to defining a probable intermediate common to both the dehydrogenase and esterase reactions are reported.
Abstract: Human liver aldehyde dehydrogenase has been found to be capable of hydrolyzing p-nitrophenyl esters. Esterase and dehydrogenase activities exhibited identical ion exchange and affinity properties, indicating that the same protein catalyzes both reactions. Competitive inhibition of esterase activity by glyceraldehyde and chloral hydrate furnished evidence that p-nitrophenyl acetate was hydrolyzed at the aldehyde binding site for dehydrogenase activity. Pyridine nucleotides modified esterase activity; NAD+ accelerated the rate of p-nitrophenyl acetate hydrolysis more than 5-fold, whereas NADH increased activity by a factor of 2. Activation constants of 117 pM for NAD+ and 3.5 pM for NADH were obtained from double reciprocal plots of initial rates as a function of modifier concentration at pH 7. The kinetics of activation of ester hydrolysis were consistent with random addition of pyridine nucleotide modifier and ester substrate to this enzyme. Several NAD+-dependent dehydrogenases are capable of catalyzing the hydrolysis of p-nitrophenyl acetate, an exten- sivcly employed model substrate for esterases (l-4). Such a dual reaction specificity, associated with an enzyme not primarily classified among the hydrolases, was first reported for glyceraldehyde-3-phosphate dehydrogenase in 1961 (1). Detailed kinetic studies of the esterolytic activity of this enzyme contributed to the elucidation of the nature of a key acyl intermediate formed during the dehydrogenase reaction (1, 2). More recently, horse liver aldehyde dehydrogenase (3), and a-glycerol phosphate dehydrogenase (4) also have been shown to hydrolyze p-nitrophenyl acetate. The hydrolysis of this ester by glyceraldehyde-3-phosphate dehydrogenase and by horse liver aldehyde dehydrogenase has been shown to take place at the same catalytic center which is responsible for dehydrogenase activity. Human liver aldehyde dehydrogenase, which catalyzes the oxidation of both aliphatic and aromatic aldehydes to their corresponding carboxylic acids, also pos- sesses the ability to hydrolyze p-nitrophenyl esters. This paper reports on the properties of this esterase activity and their implications with respect to defining a probable intermediate common to both the dehydrogenase and esterase reactions.
TL;DR: Using animals of this age, it was shown that both cycloheximide and actinomycin D block this response to phenobarbital, which decreases heat stability of crude preparations of the enzyme from RR rats, but increases heat stability from rr animals.
01 Jan 1975
TL;DR: The aldehyde dehydrogenase (Ald D) activity of autochthonous rat hepatomas induced by AAF averages a great deal higher than in normal rat liver, and the hepatoma Ald D activity is more stable than that of normal liver to temperature, urea, and pH extremes.
Abstract: . The aldehyde dehydrogenase (Ald D) activity of autochthonous rat hepatomas induced by AAF averages a great deal higher than in normal rat liver. The hepatoma Ald D activity is more stable than that of normal liver to temperature, urea, and pH extremes. Its subcellular distribution is different, the hepatoma enzyme showing a greater proportion in the cytoplasm. The hepatoma enzyme appears to be aldehyde:NAD(P) oxidoreductase, EC 1.2.1.5, in contrast to the normal liver enzyme, which is aldehyde:NAD oxidoreductase, EC 1.2.1.3. The enzyme properties which we here designate as “hepatoma-like”are only slightly observed in the four minimal deviation (repeatedly retransplanted) hepatomas which we have examined, and are not at all observed in spontaneous hepatomas of the mouse or mastomy, nor in fetal or regenerating liver of the rat. Difficulties encountered due to the concomitant presence of the corresponding aldehyde oxidase and of “nothing dehydrogenase” are discussed.
01 Jan 1975
TL;DR: With the exception of glycerate kinase, all enzymes involved in fructose metabolism were found in the human cortex and medulla and the enzyme levels in the medulla were low in comparison with the cortex.
Abstract: Activities of enzymes involved in fructose metabolism were measured in samples of human kidney cortex and medulla. The enzymes are ketohexokinase, aldolase, NAD- and NADP-dependent alcohol dehydrogenase, aldehyde dehydrogenase, triokinase and glycerate kinase; hexose biphosphatase and sorbitol dehydrogenase were also investigated. With the exception of glycerate kinase, all enzymes involved in fructose metabolism were found in the human cortex and medulla. The enzyme levels in the medulla were low in comparison with the cortex.
TL;DR: Human liver aldehyde dehydrogenase was inhibited by aromatic chelating agents, however, structurally related compounds with much lower metal-complexing ability displayed affinities for enzyme essentially equal to those of their respectiveChelating analogues.
Abstract: Human liver aldehyde dehydrogenase was inhibited by aromatic chelating agents. However, structurally related compounds with much lower metal-complexing ability displayed affinities for enzyme essentially equal to those of their respective chelating analogues. Inhibition was competitive with respect to the coenzyme. It is suggested that hydrophobic interactions between the inhibitors and the coenzyme-binding site of the enzyme are responsible for the observed effects on activity.
TL;DR: Chronic ingestion of 4-bromopyrazole caused a decrease in the natural ethanol preference of C57BL mice, a finding consistent with aldehyde dehydrogenase inhibition and the production of acetaldehyde from the interaction of4-b rompeyrazole and ethanol.
TL;DR: Nachweis, dass Pyrogallol und ähnliche Substanzen eine der mitochondrialen Alkoholdehydrogenasen aus Rattenleber hemmen wirkt.
Abstract: Nachweis, dass Pyrogallol und ahnliche Substanzen eine der mitochondrialen Alkoholdehydrogenasen aus Rattenleber hemmen.
Journal Article•
TL;DR: It is shown that ethanol drinking is unable to induce aldehyde dehydrogenase activity of hepatic cytosol in the rat, and the inducibility of the soluble alde Hyde dehydrogen enzyme activity by phenobarbital does not seem to correlate with the alcohol preference in theRat.
Abstract: Rats selected for their high or low induction by phenobarbital of the liver soluble aldehyde dehydrogenase were subjected to an ethanol preference test. In addition, rats raised by genetic selection for their preference either to drink or to avoid an ethanol solution were treated with phenobarbital to detect a possible variation in the inducibility of aldehyde dehydrogenase in hepatic cytosol. No clear correlation could be found between aldehyde dehydrogenase inducibility and ethanol preference. Phenobarbital administration to rats genetically preferring or avoiding ethanol revealed that they had a similar response so far as aldehyde dehydrogenase activity was concerned. Animals compelled to drink a 10% ethanol solution for two weeks did not exhibit any significant increase in the activities of aldehyde and D-glucuronolactone dehydrogenase. The results show that ethanol drinking is unable to induce aldehyde dehydrogenase activity of hepatic cytosol in the rat. Similarly, the inducibility of the soluble aldehyde dehydrogenase activity by phenobarbital does not seem to correlate with the alcohol preference in the rat.