Showing papers on "Aldehyde dehydrogenase published in 1978"
TL;DR: NAD-dependent acetaldehyde dehydrogenase of human tissues was investigated by electrophoresis and enzyme assay and the distribution of various phenotypes of ALDH isozyme sets is presented.
Abstract: NAD-dependent acetaldehyde dehydrogenase (ALDH) of human tissues was investigated by electrophoresis and enzyme assay. ALDH is located mainly in the liver and kidney. The isozymes consist of at least six different components. Five different phenotypes were found in a total of 68 human liver and kidney specimens. It is likely that three isozyme sets are concerned in determining ALDH types. The distribution of various phenotypes of ALDH isozyme sets is presented.
84 citations
Journal Article•
TL;DR: Experiments in vitro showed that inactivation of cytochrome P-450 by p-Xylene required the metabolic conversion of p-xylene to p-tolualdehyde, which required the presence of NADPH to carry out the inactivation.
Abstract: Rats given a single ip injection of p-xylene suffered 65% loss of pulmonary microsomal p-xylene hydroxylase activity. The activity was protected by pretreating the rats with phenobarbital, which increased hepatic p-xylene hydroxylase and cytosolic aldehyde dehydrogenase activities, but had no effect on alcohol dehydrogenase activity in hepatic cytosol. Pretreatment of rats with pyrazole caused a 60% inhibition of liver alcohol dehydrogenase but had no effect on liver aldehyde dehydrogenase activity. This treatment partially protected the pulmonary microsomal p-xylene hydroxylase from inactivation by p-xylene. Experiments in vitro showed that inactivation of cytochrome P-450 by p-xylene required the metabolic conversion of p-xylene to p-tolualdehyde. The reactive intermediate (p-tolualdehyde) required the presence of NADPH to carry out the inactivation. Inasmuch as lung tissues cannot form p-tolualdehyde (because of the low activity of p-methylbenzyl alcohol dehydrogenase), it is assumed that the inactivation of lung enzymes in vivo following exposure to p-xylene was due to the aldehyde intermediate which is formed in the liver and transported to the lung.
76 citations
TL;DR: A membrane-bound aldehyde dehydrogenase was solubilized from rat liver microsomes and purified about 150-fold by chromatography on ω-aminohexyl- and 5′-AMP-Sepharose columns with a recovery of about 40%.
71 citations
TL;DR: Rat liver contains two inducible aldehyde dehydrogenases in the cytosol, and phenobarbital, 1,1,1-trichloro-2,2-bis-(p-chlorophenylethane) (DDT), and dodecachlorooctahydro-1,3,4-metheno- 2H-cyclobuto[cd]pentalene (Mirex) induce only the φ enzyme significantly
70 citations
TL;DR: Genetic variants for ADH-C2 established its identity with a second form of sorbitol dehydrogenase observed in stomach and other tissues, which was found in high activity in liver, kidney, pancreas and male reproductive tissues.
Abstract: 1. 1. Cellulose acetate zymograms of alcohol dehydrogenase (ADH), aldehyde dehydrogenase, sorbitol dehydrogenase, aldehyde oxidase, “phenazine” oxidase and xanthine oxidase extracted from tissues of inbred mice were examined. 2. 2. ADH isozymes were differentially distributed in mouse tissues: A 2 —liver, kidney, adrenals and intestine; B 2 —all tissues examined; C 2 —stomach, adrenals, epididymis, ovary, uterus, lung. 3. 3. Two NAD + -specific aldehyde dehydrogenase isozymes were observed in liver and kidney and differentially distributed in other tissues. Alcohol dehydrogenase, aldehyde oxidase, “phenazine” oxidase and xanthine oxidase were also stained when aldehyde dehydrogenase was being examined. 4. 4. Two aldehyde oxidase isozymes exhibited highest activities in liver. 5. 5. “Phenazine oxidase” was widely distributed in mouse tissues whereas xanthine oxidase exhibited highest activity in intestine and liver extracts. 6. 6. Genetic variants for ADH-C 2 established its identity with a second form of sorbitol dehydrogenase observed in stomach and other tissues. The major sorbitol dehydrogenase was found in high activity in liver, kidney, pancreas and male reproductive tissues.
62 citations
TL;DR: A method for the purification of yeast K+-activated aldehyde dehydrogenase is presented which can be completed in substantially less time than other published procedures and suggests the presence of a dinucleotide fold in common with other dehydrogenases and kinases.
Abstract: A method for the purification of yeast K+-activated aldehyde dehydrogenase is presented which can be completed in substantially less time than other published procedures. The enzyme has a different N-terminal amino acid from preparations previously reported, and other small differences in amino acid content. These differences may be the result of differential proteolytic digestion rather than a different protein in vivo. A purification step involves the biospecific adsorption on affinity columns containing immobilized nucleotides in the absence of the substrate aldehyde. Direct binding studies with the coenzyme in the absence of aldehyde reveal 4 NAD sites per tetrameric molecule, each with a dissociation constant of 120 micron. These results conflict with properties of preparations previously reported and may conflict with kinetic models that have aldehyde as the leading substrate. Binding to Blue Dextran affinity columns suggests the presence of a dinucleotide fold in common with other dehydrogenases and kinases.
61 citations
TL;DR: It was found that acetaldehyde is metabolized in erythrocytes by NAD dependent cytosolic enzyme having an apparent Km value for acetaldehyde approximately 0.7 mM at pH 7.4, and it is suggested that ery Throcytes may have an enzyme system similar to the high Km isozyme of the liver aldehyde dehydrogenase.
56 citations
01 Jan 1978
TL;DR: The ontogenetic development of the enzymes alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenases (ALDH I and II) was followed in rats and the relative subcellular distribution of all enzymes was identical before birth, 7 days after birth and in adults.
Abstract: The ontogenetic development of the enzymes alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenases (ALDH I and II) was followed in rats. ADH could be detected just before birth and increased gradually to reach 82% of adult values at 47 days. ALDH I and II were present from day 15 of gestation, increased rapidly at birth, and reached 80-90% adult values at 47 days. The ratio between ALDH and ADH activities decreased gradually during ontogenesis. The relative subcellular distribution of all enzymes was identical before birth, 7 days after birth and in adults. The placental activities of ADH and ALDH I and II were studied at 15 and 20 days of pregnancy. ADH could not be detected in placentas. Low activities of ALDH I and II were present in placentas studied at 15 days of gestation, and still lower activities were found in placenta at 20 days.
55 citations
TL;DR: To ascertain whether synthesis or degradation of these enzymes were responsible for the marked increase in activity the turnover of several liver fractions and of the indicated enzymes were measured by the dual-labelled isotope technique.
Abstract: Levels of liver alcohol dehydrogenase, liver mitochondrial aldehyde dehydrogenase and brain (Na + K)-stimulated ATPase were determined in control rats and in rats fed an ethanol liquid diet for 7 weeks. The alcohol dehydrogenase level did not change with the diet; however, the levels of mitochondrial aldehyde dehydrogenase and of the (Na + K)-ATPase were increased 2.5-fold and 2-fold respectively.
Also, the levels of these enzymes from brain and liver fractions of rats given a 20% ethanol solution as the sole drinking fluid were determined at intervals from 4 to 18 weeks. A progressive increase was found in the level of aldehyde dehydrogenase and of ATPase.
To ascertain whether synthesis or degradation of these enzymes were responsible for the marked increase in activity the turnover of several liver fractions and of the indicated enzymes were measured by the dual-labelled isotope technique. Long-term ethanol administration did not affect the rate of turnover of the liver cell fractions except for the mitochondrial fraction. This fraction showed a marked decrease in the rate of degradation. The degradation constant of the liver alcohol dehydrogenase did not change; however, the rate of degradation of liver mitochondrial aldehyde dehydrogenase (low-Km) and of brain (Na + K)-ATPase was decreased.
51 citations
TL;DR: The results are consistent with a rapid covalent interaction between disulfiram and the enzyme, and inconsistent with the notion that disulfIRam is a reversible competitive inhibitor of cytoplasmic aldehyde dehydrogenase.
Abstract: The effect of disulfiram, [1-14C]disulfiram and some other thiol reagents on the activity of cytoplasmic aldehyde dehydrogenase from sheep liver was studied. The results are consistent with a rapid covalent interaction between disulfiram and the enzyme, and inconsistent with the notion that disulfiram is a reversible competitive inhibitor of cytoplasmic aldehyde dehydrogenase. There is a non-linear relationship between loss of about 90% of the enzyme activity and amount of disulfiram added; possible reasons for this are discussed. The remaining approx. 10% of activity is relatively insensitive to disulfiram. It is found that modification of only a small number of groups (one to two) per tetrameric enzyme molecule is responsible for the observed loss of activity. The dehydrogenase activity of the enzyme is affected more severely by disulfiram than is the esterase activity. Negatively charged thiol reagents have little or no effect on cytoplasmic aldehyde dehydrogenase. 2,2'-Dithiodipyridine is an activator of the enzyme.
47 citations
TL;DR: Evidence from alternative substrate analysis and product-inhibition studies supports an ordered sequence of substrate binding in which NAD+ is the leading substrate, and the order of substrate addition proposed here differs from that proposed for a yeast aldehyde dehydrogenase previously reported.
Abstract: Data from steady-state kinetic analysis of yeast K+-activated aldehyde dehydrogenase are consistent with a ternary complex mechanism. Evidence from alternative substrate analysis and product-inhibition studies supports an ordered sequence of substrate binding in which NAD+ is the leading substrate. A preincubation requirement for NAD+ for maximum activity is also consistent with the importance of a binary enzyme-NAD+ complex. Dissociation constant for enzyme-NAD+ complex determined kinetically is in reasonable agreement with that determined by direct binding. The order of substrate addition proposed here differs from that proposed for a yeast aldehyde dehydrogenase previously reported. Different methods of purification produced an enzyme that showed similar kinetic characteristics to those reported here.
TL;DR: It is argued that inherent variation in brain ALDH activity may be a principal biochemical counterpart of the differences in ethanol intake among different strains and sexes of laboratory rats.
Abstract: Voluntary ethanol consumption and brain and liver aldehyde dehydrogenase (ALDH) activity were measured in male and female rats of the Tryon Maze-Bright (S1), Tryon Maze-Dull (S3), and Wistar strains. The levels of brain ALDH measured in the different groups corresponded well to the levels of ethanol consumption, while differences in liver ALDH corresponded well to only the strain differences in ethanol intake. Within individual groups, levels of brain than liver aldehyde-oxidizing capacity. Age affected both voluntary ethanol intake and liver ALDH levels, but there were no systematic relations between the two effects. Age did not significantly affect the cerebral-aldehyde oxidizing capacity. It is argued that inherent variation in brain ALDH activity may be a principal biochemical counterpart of the differences in ethanol intake among different strains and sexes of laboratory rats.
TL;DR: This paper is the first report of occurrence of aldehyde dehydrogenase (EC 1.2.1.3) in blood and the results demonstrating and identifying alde Hyde dehydrogenases in human blood are presented.
TL;DR: Arguments are presented for the existence of distinct ester- and aldehyde-binding sites and NAD+ and NADH stimulated the steady-state rate of ester hydrolysis at concentrations expected on the basis of their Michaelis constants from the dehydrogenase reaction.
Abstract: The hydrolysis of 4-nitrophenyl acetate catalysed by cytoplasmic aldehyde dehydrogenase (EC 1.2.1.3) from sheep liver was studied by steady-state and transient kinetic techniques. NAD+ and NADH stimulated the steady-state rate of ester hydrolysis at concentrations expected on the basis of their Michaelis constants from the dehydrogenase reaction. At higher concentrations of the coenzymes, both NAD+ and NADH inhibited the reaction competitively with respect to 4-nitrophenyl acetate, with inhibition constants of 104 and 197 micron respectively. Propionaldehyde and chloral hydrate are competitive inhibitors of the esterase reaction. A burst in the production of 4-nitrophenoxide ion was observed, with a rate constant of 12 +/- 2s-1 and a burst amplitude that was 30% of that expected on the basis of the known NADH-binding site concentration. The rate-limiting step for the esterase reaction occurs after the formation of 4-nitrophenoxide ion. Arguments are presented for the existence of distinct ester- and aldehyde-binding sites.
TL;DR: The use of aldehyde-metabolizing enzymes inhibitors may help to reveal the real values of diamine oxidase activity, when tissues homogenates are used as a source of enzyme.
TL;DR: The data suggest that induction of brain ALDH activity may reflect a physiological mechanism that mediates the adaptation of neurones in the brain to some of the acetaldehyde-mediated effects of ethanol.
Journal Article•
TL;DR: 2,3-Dihydroxybutyraldehyde at nontoxic doses slowed down the growth of solid and ascites tumors in mice and suggest a possible relationship between the lack of this enzyme activity and the antitumor activity of aliphatic aldehydes.
Abstract: The antitumor activity of 2,3-dihydroxybutyraldehyde on Ehrlich carcinoma, Sarcoma 180, and Yoshida AH 130 hepatoma, as well as the aldehyde dehydrogenase activity in these tumors, was studied. 2,3-Dihydroxybutyraldehyde at nontoxic doses (500 mg/kg body weight i.p. daily for 7 days) slowed down the growth of solid and ascites tumors in mice. The same treatment completely prevented the development of Yoshida ascites hepatoma in several rats. 2,3-Dihydroxybutyraldehyde, although it did not influence the growth of Ehrlich carcinoma transplanted in the brain of mice, significantly decreased in the lungs of these animals the number of viable tumor cells that derived from the primary tumor. All the tested tumors, which were sensitive to the action of 2,3-dihydroxybutyraldehyde, were virtually devoid of aldehyde dehydrogenase activity. These results suggest a possible relationship between the lack of this enzyme activity and the antitumor activity of aliphatic aldehydes.
TL;DR: In this article, it was shown that C21 steroids with the 20-oxo-21-aldehyde side chain (isocorticosteroids) are oxidized by horse liver aldehyde dehydrogenases to 20-hydroxy-21 -oic acids.
TL;DR: A NAD+-dependent aldehyde dehydrogenase, the activity of which induces at the same time as luceriferase, has been purified from the bioluminescent bacterium Beneckea harveyi, and its chemical and physical properties have been investigated.
TL;DR: Clearcut regional differences in DA catabolism occur in the brain of the living animal, which may depend upon the characteristics of the dopaminergic-rich area of the rat's brain.
TL;DR: Repeated sessions of electrical stimulation or lesions in the ventral aspect of the medial forebrain bundle (VMFB) region of the brain in rats resulted in a significant increase and a decrease in voluntary ethanol intake and in levels of liver ALDH activity.
Abstract: Repeated sessions of electrical stimulation or lesions in the ventral aspect of the medial forebrain bundle (VMFB) region of the brain in rats resulted in a significant increase and a decrease in voluntary ethanol (10% v/v) intake, respectively. Whole brain and midbrain-diencephalon (MB-DE) aldehyde dehydrogenase (ALDH) were measured in different groups of experimental and control animals before, immediately after, and 30 days after the termination of the stimulation regimen, or 8 days and 30 days after the induction of the lesions. By the end of the stimulation regimen, the levels of MB-DE ALDH of the experimental (ethanol-drinking: stimulated) animals were significantly higher than those of control animals (ethanol-drinking: nonstimulated, water-drinking: stimulated, and water-drinking: nonstimulated). A marked decrease in MB-DE ALDH activity was noted in lesioned animals but not in cyanamide-treated or in implanted control animals. Neither the stimulation nor the lesions had any demonstrable effect on whole brain ALDH activity. Cyanamide administration caused a pronounced decrease in ethanol intake and in levels of liver ALDH activity. The increase in MB-DE ALDH activity in the ethanol-drinking, stimulated animals was attributed to the interaction between the VMFB activation and the ethanol drinking, while the reduction in ALDH activity was attributed to the degeneration of biogenic-amine-containing nerve fibers.
Journal Article•
TL;DR: Propiolaldehyde, a theoretically possible product of metabolism of all three of the above compounds, was implicated as the active metabolite responsible for AlDH inhibition, essentially completely inhibited the low Km AlDH of intact rat liver mitochondria.
Abstract: Pargyline (Eutonyl) inhibited aldehyde dehydrogenase (AlDH) in vivo in rats as adduced by the elevation of ethanol-derived blood acetaldehyde (AcH), but had no effect in vitro on the enzyme in intact mitochondria. SKF-525A, an inhibitor of the hepatic microsomal P-450 enzyme system, completely prevented the pargyline-induced elevation of blood AcH in vivo, further implicating a metabolite of pargyline as the active inhibitor of AlDH. Of the potential pargyline metabolites tested, N-benzylpropargylamine and propargyl alcohol--like pargyline itself--readily inhibited AlDH in vivo but were without effect on the enzyme in vitro. These data implicated propiolaldehyde, a theoretically possible product of metabolism of all three of the above compounds, as the active metabolite responsible for AlDH inhibition. Indeed, propiolaldehyde at a concentration of 200 micron essentially completely inhibited the low Km AlDH of intact rat liver mitochondria.
TL;DR: In the presence of acetic anhydride, liver aldehyde dehydrogenases catalyse the oxidation of NADH at pH 7.0 and 25 degrees C as discussed by the authors.
Abstract: In the presence of acetic anhydride or butyric anhydride, liver aldehyde dehydrogenases catalyse the oxidation of NADH at pH 7.0 and 25 degrees C. The maximum velocities and Michaelis constants for NADH at saturating anhydride concentrations are independent of which anhydride is used, the values being V'max. = 12 min-1 and Km for NADH = 9 micrometer for the mitochondrial enzyme and V'max = 25 min-1 and Km for NADH = 20 micrometer for the cytoplasmic enzyme. Substitution of [4A-2H]NADH for NADH resulted in 2-fold and 4-fold decreases in rate for the mitochondrial and cytoplasmic enzymes respectively.
TL;DR: The effect of phenobarbital on activities of aldehyde dehydrogenases in the subcellular fractions was studied in vivo in rats of three strains and no difference among the strains was observed in the responses of the mitochondrial and microsomal enzymes.
TL;DR: In hepatomas, 15% of the total aldehyde dehydrogenase activity is immunochemically identical to the normal liver cross-reacting material which is characterizable as hepatoma specific on the basis of these immunochemical studies.
TL;DR: Direct evidence is provided that the synthesis of aldehyde dehydrogenase but not NAD(P)H:flavin oxidoreductase is induced during the development of bioluminescence.
Abstract: The proteins of the bioluminescent bacterium Beneckea harveyi have been labelled with [3H]leucine prior to the induction of bioluminescence, and with [14C]leucine during the development of the bioluminescent system. An aliphatic aldehyde dehydrogenase and a NAD(P)H: flavin oxidoreductase, two enzymes that may be directly involved in the metabolism of the substrates (aldehyde, FMNH2) for the luminescent reaction catalyzed by luciferase, were purified and the isotope ratios of their respective polypeptide chains determined after sodium dodecyl sulfate gel electrophoresis. A comparison of these isotope ratios to (a) the isotope ratios of the induced polypeptide chains of luciferase, purified in the same experiment, and (b) the average isotope ratio for the proteins synthesized in concert with growth has provided direct evidence that the synthesis of aldehyde dehydrogenase but not NAD(P)H: flavin oxidoreductase is induced during the development of bioluminescence.
01 Jan 1978
TL;DR: The present article updates the subject of monoamine biosynthesis and, perhaps, introduces a somewhat different point of view on catechol O-methyltransferase, which is introduced here as an important enzyme incatecholamine metabolism.
Abstract: The following methodological monographs detail procedures that we and others have found useful for some of the enzymes concerned with monoamine biosynthesis and metabolism. Numerous references to specific articles in the literature have been provided to aid the reader, who may also wish to consult some of the excellent compendia that have appeared in recent years. Among these are the chapter by Creveling and Daly (1971) and the volume written by Nagatsu (1973), as well as those edited by Tabor and Tabor (1971) and Kopin (1972). The enzymes of monoamine biosynthesis have been dealt with previously in this series by Goldstein (1972). The present article updates the subject and, perhaps, introduces a somewhat different point of view. Youdim (1975) and Jarrott (1975) have written recently about monoamine oxidase in Volume 3 of this series, so this enzyme does not merit a new section at this time. However, catechol O-methyltransferase is introduced here as an important enzyme in catecholamine metabolism. The organic product of the action of monoamine oxidase is an aldehyde which undergoes at least one more reaction in its terminal metabolism: either reduction to an alcohol or dehydrogenation to the corresponding acid. The enzymes catalyzing these respective reactions are described now.
TL;DR: Cross-linking patterns obtained with yeast aldehyde dehydrogenase after treatment with a series of diimidoesters of increasing chain lengths with different reaction times resulted in the appearance of tetramers as the largest cross-linked product of the enzyme subunits.
Abstract: The molecular w:ight of yeast aldehyde dehydrogenase determined by sucrose density gradient centrifugation was 207,000 +/- 13,000. The enzyme activity was proportional to the enzyme concentration in the range of 2 X 10(-11) M to 1 X 10(-7) M. Cross-linking patterns obtained with yeast aldehyde dehydrogenase after treatment with a series of diimidoesters of increasing chain lengths with different reaction times resulted in the appearance of tetramers as the largest cross-linked product of the enzyme subunits. The molecular weights of its monomer, dimer, trimer, and tetramer were, 57,000, 114,000, 171,000, and 228,000, respectively, as estimated from their mobilities on SDS-electrophoresis. In tetramers monomers are probably assembled in a heterologous square arrangement.