Showing papers on "Aldehyde dehydrogenase published in 1973"
TL;DR: Kinetic experiments suggested the possible existence of at least two different NAD(+)-dependent aldehyde dehydrogenases in rat liver and distribution studies showed that one enzyme, designated enzyme I, was exclusively localized in the mitochondria and that another enzyme, designate enzyme II, was localized in both the mitochondia and the microsomal fraction.
Abstract: 1. Kinetic experiments suggested the possible existence of at least two different NAD(+)-dependent aldehyde dehydrogenases in rat liver. Distribution studies showed that one enzyme, designated enzyme I, was exclusively localized in the mitochondria and that another enzyme, designated enzyme II, was localized in both the mitochondria and the microsomal fraction. 2. A NADP(+)-dependent enzyme was also found in the mitochondria and the microsomal fraction and it is suggested that this enzyme is identical with enzyme II. 3. The K(m) for acetaldehyde was apparently less than 10mum for enzyme I and 0.9-1.7mm for enzyme II. The K(m) for NAD(+) was similar for both enzymes (20-30mum). The K(m) for NADP(+) was 2-3mm and for acetaldehyde 0.5-0.7mm for the NADP(+)-dependent activity. 4. The NAD(+)-dependent enzymes show pH optima between 9 and 10. The highest activity was found in pyrophosphate buffer for both enzymes. In phosphate buffer there was a striking difference in activity between the two enzymes. Compared with the activity in pyrophosphate buffer, the activity of enzyme II was uninfluenced, whereas the activity of enzyme I was very low. 5. The results are compared with those of earlier investigations on the distribution of aldehyde dehydrogenase and with the results from purified enzymes from different sources.
396 citations
TL;DR: This strain was used to show that the products of meta ring fission of the cresols and phenol are metabolized as follows: ortho- and meta-cresol exclusively by a hydrolase; para- cresol entirely by a NAD(+)-dependent aldehyde dehydrogenase; phenol by both a NAD (+)- dependent dehydrogen enzyme and a Hydrolase in the approximate ratio of 5 to 1.
Abstract: Mutant strains of Pseudomonas putida strain U have been obtained which are deficient in enzymes of the degradative pathways of phenol and cresols. Mutant strains deficient in catechol 2, 3-oxygenase accumulated the appropriate catechol derivative from cresols. A mutant strain which would not grow on either phenol or a cresol was shown to be deficient in both 2-hydroxymuconic semialdehyde hydrolase and a nicotinamide adenine dinucleotide, oxidized form, (NAD+)-dependent aldehyde dehydrogenase. When this strain was grown in the presence of phenol or a cresol, the appropriate product of meta fission of these compounds accumulated in the growth medium. A partial revertant of this mutant strain, which was able to grow on ortho- and meta-cresol but not para-cresol, was shown to have regained only the hydrolase activity. This strain was used to show that the products of meta ring fission of the cresols and phenol are metabolized as follows: (i) ortho- and meta-cresol exclusively by a hydrolase; (ii) para-cresol exclusively by a NAD+-dependent aldehyde dehydrogenase; (iii) phenol by both a NAD+-dependent dehydrogenase and a hydrolase in the approximate ratio of 5 to 1. This conclusion is supported by the substrate specificity and enzymatic activity of the hydrolase and NAD+-dependent aldehyde dehydrogenase enzymes of the wild-type strain. The results are discussed in terms of the physiological significance of the pathway. Properties of some of the mutant strains isolated are discussed.
121 citations
TL;DR: The results are discussed with regard to the oxidation of acetaldehyde and to the transfer of reducing equivalents from cytosol to mitochondria during ethanol metabolism.
Abstract: 1
The primary product of the well-known oxidation of acetaldehyde by rat liver mitochondria is acetate. About 50% of the acetate formed from acetaldehyde is converted to ketone bodies under the experimental conditions used.
2
The oxidation of acetaldehyde by rat liver mitochondria is catalyzed mainly by an aldehyde: NAD oxidoreductase present in the matrix compartment of the mitochondria. About 20% of the total mitochondrial acetaldehyde dehydrogenase activity may be confined to the outer membrane or the intermembrane space.
3
The enzyme has a broad substrate specificity, pH-optimum at about pH 9.0 and is inhibited by tetraethylthiuram disulfide, chloral hydrate and arsenite. The enzyme is steroid-insensitive.
Two Km-values for acetaldehyde, below 0.1 μM and 1.0 mM, and two Km-values for NADM+, 2 μM and 50 μM, were obtained with a partially purified 100000 ×g supernatant. The presence of two aldehyde dehydrogenases in rat liver mitochondria could not be shown.
4
Oxidation of acetaldehyde by rat liver mitochondria causes an inhibition of the production of 14Co2, from [14C]palmitate. The inhibition can be accounted for by dilution of the acetyl-coenzyme A pool of the mitochondria.
The 3-hydroxybutyrate/acetoacetate ratio during acetaldehyde oxidation is kept at the same level as during oxidation of oleate plus coenzyme A.
5
The mitochondrial acetaldehyde dehydrogenase activity is 80% of the total acetaldehyde dehydrogenase activity of rat liver. The results are discussed with regard to the oxidation of acetaldehyde and to the transfer of reducing equivalents from cytosol to mitochondria during ethanol metabolism.
96 citations
TL;DR: Evidence is presented for the existence of an intraneuronal 'dopamine monoamine oxidase' and intraneURonal aldehyde dehydrogenase and their activity was significantly reduced in the striatum of rats 8 days after lesion of the nigrostriatal nerve pathway caused by 6-hydroxydopamine.
Abstract: Monoamine oxidase and aldehyde dehydrogenase activity were significantly reduced in the striatum of rats 8 days after lesion of the nigrostriatal nerve pathway caused by 6-hydroxydopamine. Evidence is presented for the existence of an intraneuronal 'dopamine monoamine oxidase' and intraneuronal aldehyde dehydrogenase. Dopamine concentrations were reduced to 10% of their control values.
59 citations
TL;DR: Comparison of crude and partially purified aldehyde dehydrogenase preparations (aldehyde:NAD+ oxidoreductase, EC 1.2.1.3) from the cytosolic compartment and from the mitochondria of the rat liver indicates that two different enzymes are involved.
41 citations
TL;DR: Growth, microrespirometric and enzymic evidence implicated amino alcohol O-phosphates as aldehyde precursors and an inducibly formed ATP-amino alcohol phosphotransferase was partially purified and found to be markedly stimulated by ADP, unaffected by NH(4) (+) ions and more active with ethanolamine than with 1-aminopropan-2-ol compounds.
Abstract: 1. Growth of Erwinia carotovora N.C.P.P.B. 1280 on media containing 1-aminopropan-2-ol compounds or ethanolamine as the sole N source resulted in the excretion of propionaldehyde or acetaldehyde respectively. The inclusion of (NH4)2SO4 in media prevented aldehyde formation. 2. Growth, microrespirometric and enzymic evidence implicated amino alcohol O-phosphates as aldehyde precursors. An inducibly formed ATP–amino alcohol phosphotransferase was partially purified and found to be markedly stimulated by ADP, unaffected by NH4+ ions and more active with ethanolamine than with 1-aminopropan-2-ol compounds. Amino alcohol O-phosphates were deaminated by an inducible phospho-lyase to give the corresponding aldehydes. This enzyme, separated from the kinase during purification, was more active with ethanolamine O-phosphate than with 1-aminopropan-2-ol O-phosphates. Activity of the phospho-lyase was unaffected by a number of possible effectors, including NH4+ ions, but its formation was repressed by the addition of (NH4)2SO4 to growth media. 3. E. carotovora was unable to grow with ethanolamine or 1-aminopropan-2-ol compounds as sources of C, the production of aldehydes during utilization as N sources being attributable to the inability of the microbe to synthesize aldehyde dehydrogenase. 4. Of seven additional strains of Erwinia examined similar results were obtained only with Erwinia ananas (N.C.P.P.B. 441) and Erwinia milletiae (N.C.P.P.B. 955).
21 citations
TL;DR: Both 3α,7α,12α-trihydroxy-5β-cholestan-26-al dehydrogenase and horse liver aldehyde:NAD+ oxidoreductase were reduced to a similar extent on inactivation of the purified enzyme by heating or by incubation with p-chloromercuribenzoate.
18 citations
TL;DR: It is reported here that acetaldehyde (0.6-4.5 mM) is a potent inhibitor of the reconstituted malate-aspartate, a-glycerophosphate and fatty acid shuttles for the transport of reducing equivalents into mitochondria.
13 citations
TL;DR: The enzyme was purified 60- to 70-fold and retained broad specificity for a variety of aliphatic and aromatic aldehydes and was protected from inactivation by NAD+, but was otherwise unstable.
12 citations
Journal Article•
TL;DR: A reaction pathway is proposed which involves hydroxylation of a methyl group on the N- tert.
Abstract: The characteristics of the enzyme system which catalyzes the N-dealkylation of N- tert. -butylnorchlorcyclizine have been studied. The reaction requires oxygen, reduced nicotinamide adenine dinucleotide phosphate, nicotinamide adenine dinucleotide, microsomes and cytoplasm and is inhibited by cyanide, semicarbazide, o -phenanthroline, disulfiram, pyrazole, SKF 525A and carbon monoxide. The requirement for cytoplasm can be replaced by alcohol or aldehyde dehydrogenase. The reaction is induced by pretreatment with phenobarbital and is inhibited by pretreatment with carbon tetrachloride. A reaction pathway is proposed which involves hydroxylation of a methyl group on the N- tert. -butyl side chain by the microsomal mixed function oxidase system followed by stepwise oxidation to a carboxylic acid by soluble enzymes which require nicotinamide adenine dinuncleotide. The carboxylic acid is decarboxylated and the resulting N-isopropyl derivative is N-dealkylated by microsomal mixed function oxidases to norchlorcyclizine.
11 citations
TL;DR: Inhibition of the oxidation by pretreatment in vivo with disulfiram suggests the involvement of a myocardial aldehyde dehydrogenase, which may be rate-limiting since acetate oxidation to carbon dioxide proceeds faster than acetaldehyde oxidation in the perfused rat heart.
Abstract: SummaryIsolated beating rat hearts perfused with [1,2-14C] acetaldehyde oxidize the compound to 14CO2. Inhibition of the oxidation by pretreatment in vivo with disulfiram suggests the involvement of a myocardial aldehyde dehydrogenase. The dehydrogenation of acetaldehyde may be rate-limiting since acetate oxidation to carbon dioxide proceeds faster than acetaldehyde oxidation in the perfused rat heart.We are grateful to Steve Altman for helpful discussion and technical assistance.
TL;DR: The properties of the enzyme, in particular its kinetic parameters, the influence of temperature, its sensitivity to inhibitors of -SH groups, the nature of coenzyme suggest that alkane-oxidation can be performed by two enzymes, one of them is soluble and the other particulate as has been described previously in the case of Candida tropicalis.
Journal Article•
TL;DR: From these enzymatic results propranolol has the potential of slowing ethanol oxidation, and since aldehyde dehydrogenase is involved in the catabolism of the biogenic amines, proPRanolol may modify the metabolism of the deaminated biogenicAmines.
Abstract: Propranolol inhibits horse liver alcohol dehydrogenase (EC 1.1.1.1), yeast alcohol dehydrogenase (EC 1.1.1.1), and pig brain aldehyde dehydrogenase (EC 1.2.1.3). In each case the inhibition is reversible. The form of the inhibitions is consistent with the formation of an enzyme-propranolol complex which in some cases may bind the coenzyme. Various kinetic constants for the inhibitions have been calculated; K i values lie between 100 and 360 µM for these enzymes. Propranolol increases the dissociation constants of both 59-AMP and phenanthroline from their complexes with liver alcohol dehydrogenase, but ternary complexes of enzyme with propranolol and 59-AMP or phenanthroline are formed. Propranolol in concentrations up to 1 mM inhibits neither rat liver lactate dehydrogenase (EC 1.1.1.27) nor malate dehydrogenase (EC 1.1.1.37) from rat liver or from pig heart. Pronethalol inhibits liver alcohol dehydrogenase with a K i slope value of 84 µM. From these enzymatic results propranolol has the potential of slowing ethanol oxidation, and since aldehyde dehydrogenase is involved in the catabolism of the biogenic amines, propranolol may modify the metabolism of the deaminated biogenic amines.
TL;DR: Evidence has been obtained which indicates that the NADPH-linked aldehyde reductase, alcohol:NADP oxidoreductase, but not the NADH-dependent enzyme, may be involved in the reduction of biogenic aldehydes including the catecholaldehydes in brain.
TL;DR: A study of aldehyde dehydrogenase in rat hepatomas cells and rat hepatoma-mouse fibroblast hybrids revealed that the hepatoma cells had activity comparable to that found in whole rat liver and that the enzyme activity was suppressed in early hybrids and reappeared following chromosome loss.
Abstract: A study of aldehyde dehydrogenase in rat hepatoma cells and rat hepatoma-mouse fibroblast hybrids revealed that the hepatoma cells had activity comparable to that found in whole rat liver and that the enzyme activity was suppressed in early hybrids and reappeared following chromosome loss. Starch gel electrophoresis and heat inactivation studies showed that a new form of enzyme was produced in the hybrids, possibly a heteropolymorphic combination between the HTC enzyme and a previously repressed mouse form. Staining methods for starch gel electrophoresis and histochemical detection of aldehyde dehydrogenase are described.
TL;DR: Results are interpreted to mean that the active site is complete in the absence of K+, which is considerably smaller than the likely rate of K+ dissociation from the enzyme.