Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: CAS:75-07-0 (aldehyde)
 25,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of hypolipidemic drug clofibrate on the activity of aldehyde dehydrogenase with different substrates was studied in subcellular fractions of rat liver homogenate. It was shown that under the action of clofibrate the content of the enzyme was increased 2-3-fold in purified peroxisomal fraction as well as in microsomes and mitochondria. No difference was found in the cytoplasmic fraction. Partial purification of clofibrate-induced aldehyde dehydrogenase from microsomes was undertaken. The enzyme is apparently membrane-bound. It has a molecular weight of 187,000 and a subunit size of 47,000, indicating that the molecule is a tetramer. An induced aldehyde dehydrogenase is active with several aliphatic and aromatic aldehydes but not with formaldehyde and glyceraldehyde. The enzyme has Km-values in the millimolar range for acetaldehyde, propionaldehyde, benzaldehyde and phenylacetaldehyde and in the micromolar range for nonanal. Both NAD and NADP serve as coenzymes for the purified aldehyde dehydrogenase. According to substrate specificity, kinetic and molecular properties clofibrate-induced aldehyde dehydrogenase appears to be identical to normal liver microsomal enzyme.
 ...
PMID:Subcellular distribution and properties of a clofibrate-induced aldehyde dehydrogenase from rat liver. 397 Jul 18

The in vitro oxidation of benzaldehyde and acetaldehyde was studied in liver samples from disulfiram-treated and control rats. With 25 microM substrate, both cytosol and mitochondria appeared to make a nearly equal contribution to the oxidation of benzaldehyde, whereas ca. 90% of acetaldehyde oxidation occurred in mitochondria. When the Km values for benzaldehyde with aldehyde dehydrogenase (ALDH) were determined, two Km values (3 and 120 microM) were obtained with mitochondria, but only a single Km value (25 microM) was obtained with the cytosolic fraction. The relatively high Km (2.9 mM) found with microsomes makes it unlikely that microsomes are important in the oxidation of benzaldehyde. In intact mitochondria, with 200 microM acetaldehyde or benzaldehyde the matrix space enzyme accounted for 77 and 62%, respectively, of the total ALDH activity. When the activity was determined in a mixture containing both substrates, the activity was found not to be additive, indicating that both substrates are oxidized by the same matrix space enzyme. With subcellular fractions, from livers of disulfiram-treated and control rats, a greater degree of inhibition of ALDH was obtained when acetaldehyde was a substrate compared to that with benzaldehyde in cytosol and mitochondria. Microsomal ALDH was not inhibited by disulfiram. In liver slices from rats given disulfiram, a statistically significant inhibition was found when either 25 or 250 microM acetaldehyde was used (46 and 33%). With benzaldehyde, a significant inhibition (24%) was observed only with the lower substrate concentration. Finding that both mitochondrial fractions and slices were less inhibited at the higher substrate concentration implies that the high Km enzyme is not inhibited. It can be concluded that, in rat, disulfiram inhibiting liver ALDH not only affects oxidation of acetaldehyde, but also that of benzaldehyde.
 ...
PMID:Effects of disulfiram on the oxidation of benzaldehyde and acetaldehyde in rat liver. 399 63

The aim of this work was to study the role of hydrophobic interactions in the enzymic activity of chymotrypsin. The amino groups of chymotrypsin were chemically modified by aliphatic aldehydes of various chain lengths - acetaldehyde, butyraldehyde, hexanal - and with two aldehydes of different steric hindrance - benzaldehyde and trimethyl acetaldehyde. After a rapid study of the derivated enzymes, the hexylchymotrypsin has been chosen for its new catalytic properties: the Michaelis constant is not modified and the maximal velocity with N-glutaryl-L-phenylalanine-4-nitroaniline is increased to 164%. The increase is due to the increase of the acylation constant, k2, by 230%. The value of k3 is not modified or less modified. In the modified enzyme, 85% of free amino acids are still able to react with trinitrobenzenesulphonic acid. The optimum pH is shifted by one pH unit towards the alkaline pH. The thermodynamic study shows that the catalytic process itself is not modified. The increase in Vm could be a simple increase of k2 linked to a modification of the site or of the protein. The phenomenon described is very specific and obtained only with one modification, hexanal, and with one enzyme, alpha-chymotrypsin.
 ...
PMID:Microenvironmental effects on enzyme catalysis. A kinetic study of hydrophobic derivatives of chymotrypsin. 399 46

A study was made of the effect of chronic administration of the hypolipidemic drug clofibrate on the activity and intracellular localization of rat liver aldehyde dehydrogenase. The enzyme was assayed using several aliphatic and aromatic aldehydes. Clofibrate treatment caused a 1.5 to 2.3-fold increase in the liver specific aldehyde dehydrogenase activity. The induced enzyme has a high Km for acetaldehyde and was found to be located in peroxisomes and microsomes. Clofibrate did not alter the enzyme activity in the cytoplasmic fraction. The total peroxisomal aldehyde dehydrogenase activity increased 3 to 4-fold under the action of clofibrate. Disruption of the purified peroxisomes by the hypotonic treatment or in the alkaline conditions resulted in the release of catalase from the broken organelles, while aldehyde dehydrogenase as well as nucleoid-bound urate oxidase and the peroxisomal membrane marker NADH:cytochrome c reductase remained in the peroxisomal 'ghosts'. At the same time, treatment by Triton X-100 led to solubilization of the membrane-bound NADH:cytochrome c reductase and aldehyde dehydrogenase from intact peroxisomes and their 'ghosts'. These results indicate that aldehyde dehydrogenase is located in the peroxisomal membrane. The peroxisomal aldehyde dehydrogenase is active with different aliphatic and aromatic aldehydes, except for formaldehyde and glyceraldehyde. The enzyme Km values lie in the millimolar range for acetaldehyde, propionaldehyde, benzaldehyde and phenylacetaldehyde and in the micromolar range for nonanal. Both NAD and NADP serve as coenzymes for the enzyme. Aldehyde dehydrogenase was inhibited by disulfiram, N-ethylmaleimide and 5,5'-dithiobis(2-nitrobenzoic)acid. According to its basic kinetic properties peroxisomal aldehyde dehydrogenase seems to be similar to a clofibrate-induced microsomal enzyme. The functional role of both enzymes in the liver cells is discussed.
 ...
PMID:Intraparticulate localization and some properties of a clofibrate-induced peroxisomal aldehyde dehydrogenase from rat liver. 399 98

Pretreatment of Fischer-344 (F-344) rats with formaldehyde (HCHO) induces significant cross tolerance to the sensory irritation properties of Cl2. The purpose of this study was to determine if HCHO pretreatment would cause sensory irritation cross tolerance to other inhaled aldehydes. Male F-344 rats, weighing 190 to 210 g, were pretreated with 15 ppm HCHO, 6 hr/day for 9 days, and challenged on the 10th day with a saturated (acetaldehyde, propionaldehyde, and butyraldehyde), unsaturated (acrolein and crotonaldehyde), or cyclic (cyclohexanecarboxaldehyde, 3-cyclohexene-1-carboxaldehyde, and benzaldehyde) aldehyde. The sensory irritation response in these animals was quantified by measuring respiratory rate depression in a head-only inhalation chamber using plethysmographic techniques. Control animals were challenged identically without prior pretreatment. In naive (nonpretreated) animals, the concentration eliciting a 50% decrease in respiratory rate (RD50) was 23 ppm or less for unsaturated aliphatic aldehydes. For cyclic and saturated aliphatic aldehydes, the RD50 ranged from 600 to 1000 ppm and 3000 to 6800 ppm, respectively. Formaldehyde pretreatment resulted in cross tolerance only with acetaldehyde (RD50 increased 3.5-fold) and acrolein (RD50 increased 5-fold). These results indicate that the development of cross tolerance following HCHO pretreatment is not a general phenomenon. Prediction of acceptable concentrations of occupational exposure for the prevention of sensory irritation in humans has been based primarily on RD50 data for mice. Comparison of the RD50 values obtained for rats in this investigation with previously published results for mice varied by over one-half an order of magnitude, thereby disputing the usefulness of data from F-344 rats in setting threshold limit values for the prevention of sensory irritation.
 ...
PMID:Sensory irritation response to inhaled aldehydes after formaldehyde pretreatment. 404 1

The activities of aldehyde dehydrogenases using benzaldehyde and propionaldehyde as substrates and NADP and NAD as coenzymes were determined in normal liver, hepatocyte nodules and hepatocellular carcinomas from male Wistar rats. Hepatocyte nodules were produced by intermittent exposure of rats to 0.05% 2-acetylaminofluorene or by initiation with diethylnitrosamine followed by selection using 2 weeks of dietary exposure to 0.02% 2-acetylaminofluorene and partial hepatectomy. The activities of propionaldehyde:NAD and benzaldehyde:NADP aldehyde dehydrogenases were increased in hepatocyte nodules of all types as well as in most hepatocellular carcinomas. The most prominent elevation of enzyme activity was found in the cytosol of persistent hepatocyte nodules (35-60 times) and some hepatocellular carcinomas (92 times) using benzaldehyde and NADP. The benzaldehyde:NADP aldehyde dehydrogenase activity varied considerably between different nodules suggesting the existence of a subpopulation of hepatocyte nodules with very high enzymatic activities. The activity of propionaldehyde:NAD aldehyde dehydrogenase activity as well as of gamma-glutamyltransferase did not show substantial internodular variations. The activity of benzaldehyde:NADP aldehyde dehydrogenase in individual carcinomas investigated in these experiments varied extensively. The data did not support the idea that all hepatomas had been developed from pre-neoplastic nodules with very high activity of this enzyme.
 ...
PMID:Aldehyde dehydrogenase activities in hepatocyte nodules and hepatocellular carcinomas from Wistar rats. 406 45

HUMAN LIVER ALDEHYDE OXIDASE (ALDEHYDE: O(2) oxidoreductase, EC 1.2.3.1) has been purified 60-fold and some of its properties studied. Like aldehyde oxidase from other mammalian species, human liver aldehyde oxidase is an enzyme with dual substrate specificity, possessing the ability to catalyze not only the oxidation of aldehydes to the corresponding carboxylic acids, but also the hydroxylation of a number of nonaldehydic heterocyclic compounds; its relative activity towards the latter group of substrates is low, however, when compared with that of liver aldehyde oxidase from rabbit and guinea pig. When the aromatic aldehyde benzaldehyde is used as substrate, human liver aldehyde oxidase, like the rabbit enzyme, is strongly inhibited by menadione, estradiol-17beta, antimycin A, Triton X-100, and N-alkylphenothiazines; the human enzyme differs from the rabbit enzyme, however, in being relatively insensitive to oligomycin and Amytal. Like the rabbit enzyme, the human enzyme can catalyze the 3-hydroxylation of phenazine methosulfate (PMS) and the 6-hydroxylation of N-methylnicotinamide (NMN). With the rabbit enzyme, however, the aerobic hydroxylation of these substrates proceeds by a conventional mechanism, while with the human enzyme, the aerobic hydroxylation of PMS and NMN is anomalous in that the reaction is inhibited only by agents with affinity for the substrate-binding site, such as cyanide and N-alkylphenothiazines, and not by agents which inhibit the "internal electron transport chain" of the enzyme, such as menadione and diethylstilbestrol. This mode of oxidation appears to be unique to substrates with a positively charged quaternary nitrogen; the hydroxylation of other nonaldehydic heterocyclic substrates for the human enzyme is sensitive to conventional aldehyde oxidase inhibitors.
 ...
PMID:Human liver aldehyde oxidase: differential inhibition of oxidation of charged and uncharged substrates. 422 61

A transient release of protons with an amplitude corresponding to one proton per active site has been observed for the oxidation of propionaldehyde, acetaldehyde, and benzaldehyde by sheep liver cytoplasmic aldehyde dehydrogenase at pH 7.6 with phenol red as indicator. At saturating substrate levels, the rate constants for the proton burst are in each case the same, and for acetaldehyde and propionaldehyde show the same dependence on the concentrations of the substrates, as the rate constants for the transient production of NADH reported previously [MacGibbon, A.K.H., Blackwell, L.F., & Buckley, P.D. (1977) Biochem. J. 167, 469-477]. Although, with propionaldehyde as a substrate, a full proton burst is also observed at pH 6.0, no proton burst is observed at pH 9.0. For 4-nitrobenzaldehyde, there is no burst in NADH production, but a burst in proton release is observed, showing that proton release precedes hydride transfer. No protons were released during the binding of the substrate analogues acetone and chloral hydrate nor on reaction of the enzyme with the inhibitor tetraethylthiuram disulfide (disulfiram). A model is proposed in which the rate-limiting step in the pre-steady-state phase of the reaction is a conformational change which occurs after the binding of aldehydes to the enzyme. As a result of the conformational change, the environment of a functional group on the enzyme, which initially has a pKa of about 8.5, is perturbed to give a final pKa value for the group of less than 5. Computer simulations were used to show that the model accurately reproduces all of the experimental data. The lack of observation of a second transient proton release, as required by the overall stoichiometry, argues that its release occurs in a slow step prior to NADH dissociation.
 ...
PMID:Proton release during the pre-steady-state oxidation of aldehydes by aldehyde dehydrogenase. Evidence for a rate-limiting conformational change. 628 81

The reduction of benzaldehyde and p-nitrobenzaldehyde by NADH, catalyzed by horse liver alcohol dehydrogenase (LADH), has been found to be faster when NADH is bound to glyceraldehyde-3-phosphate dehydrogenase (GPDH) than with free NADH. The rate of reduction of aldehyde substrate with GPDH-NADH follows a Michaelian concentration dependence on GPDH-NADH. The reaction velocity is independent of GPDH concentration when [GPDH] greater than [NADH]total. The Km for GPDH-NADH is higher than that for free NADH. The reaction velocities in the presence of excess GPDH over NADH cannot be accounted for on the basis of the free NADH concentration arising from dissociation of the GPDH-NADH complex. These observations suggest that transfer of NADH from GPDH to LADH proceeds through the initial formation of a GPDH-NADH-LADH complex. Arguments for a direct enzyme-coenzyme-enzyme transfer mechanism are substantiated and quantitated both by steady-state kinetic studies and by determinations of all of the appropriate enzyme-coenzyme equilibrium dissociation constants. In contrast, over a similar concentration range, the complex lactate dehydrogenase (LDH)-NADH is not a substrate for the LADH-catalyzed reductions. Likewise, the LADH-NADH complex is not a substrate for the LDH-catalyzed reduction of pyruvate.
 ...
PMID:Direct transfer of reduced nicotinamide adenine dinucleotide from glyceraldehyde-3-phosphate dehydrogenase to liver alcohol dehydrogenase. 638 29

The class I (alpha, beta 1, gamma 1, and gamma 2), II (pi), and III (chi) isozymes of human liver alcohol dehydrogenase (ADH) were isolated as electrophoretically homogeneous preparations to examine their kinetics of aldehyde and ketone reduction. While the oxidation of a wide variety of alcohols by ADH has been investigated extensively, the reduction of aldehydes and ketones has received much less attention even though the equilibrium favors the latter process. For each isozyme, the Km and kcat values were measured at pH 7.0 with acetaldehyde, pentanal, octanal, benzaldehyde, and cyclohexanone as substrates. Activity could not be detected with succinic semialdehyde and betaine aldehyde for any of the isozymes. The nonenzymatic hydration, oxidation, and aldol condensation of aldehydes in aqueous solutions present serious experimental obstacles in determining the isozymes' kinetic constants. The effects of these reactions on the enzymatic parameters were studied and compensated for. Michaelis constants for all class I and II isozymes vary by more than 8000-fold, from less than 1 microM for beta 1 gamma 1 and beta 1 beta 1 with octanal to 8.3 mM for pi-ADH for acetaldehyde. However, with any given aldehyde, these values vary by less than 40-fold, and the constants are approximately equal to Km values reported previously for the corresponding alcohols. In contrast, Km values for chi-ADH are extremely high and could be determined accurately only for octanal (75 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Human liver alcohol dehydrogenase isozymes: reduction of aldehydes and ketones. 639 29


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>