Showing papers on "Aldehyde dehydrogenase published in 1976"

New pathway of conversion of pyridoxal to 4-pyridoxic acid.

Abstract: The only enzyme demonstrated so far to catalyze the formation of 4-pyridoxic acid, the final excretory product of vitamin B6, was aldehyde oxidase. In this paper we have presented an evidence that another enzyme, NAD+-dependent aldehyde dehydrogenase, is capable of catalyzing this reaction. Rat mutants with high, low and no aldehyde oxidase activity excrete the same amount of isotope after a single injection of 3H-pyridoxol in a 12-day experiment; 4-pyridoxic acid is also present in the urine of animals without aldehyde oxidase activity. There is no correlation between the proportion of the excreted acid and the amount of pyridoxal excreted, after the injection of a single dose of the aldehyde form. The Km values for pyridoxal and NAD+, at pH 9.6, have been found to be 75 and 260 mumol/l, respectively. NAD+-dependent pyridoxal dehydrogenase was partially purified from the rat tissues, and the following specific enzyme activities (nmol-min-1-mg-1 protein) were found: red blood cell 71.5 +/- 3.0, intestine 64.9 +/- 9.0, muscle 61.4 +/- 1.6, brain 39.5 +/- 6.0, liver 34.4 +/- 3.3, kidney 21.1 +/- 5.6, heart 18.8 +/- 0.9, and lung 6.5 +/- 2.0. This is believed to be the first report demonstrating pyridoxal oxidation, catalyzed by an NAD+-dependent aldehyde dehydrogenase.

Suppression of ethanol intake following administration of dopamine-beta-hydroxylase inhibitors in rats.

Abstract: A comparison was made between the efficacy of action of dopamine-beta-hydroxylase and/or aldehyde dehydrogenase inhibition in suppressing voluntary ethanol consumption in rats. Calcium carbimide, which caused the largest increase in blood acetaldehyde levels following ethanol injections, was the least effective in reducing ethanol consumption, whereas FLA-63, which had a smaller effect on blood acetaldehyde levels, was the most potent suppressor of ethanol ingestion. Disulfiram, which inhibits both aldehyde dehydrogenase and dopamine-beta-hydroxylase had an intermediate effect in terms of raising blood acetaldehyde levels and in suppressing ethanol intake. It is suggested that the inhibition of dopamine-beta-hydroxylase may be at least partly responsible for the suppression of ethanol intake seen following disulfiram administration, and that disruption of catecholamine synthesis may prove to be a more effective method for suppressing ethanol consumption.

The Use of Aldehyde Dehydrogenase to Determine H2O2-Producing Reactions. I. The Determination of the Uric Acid Concentration

Abstract: Summary: The sequence of reactions catalyzed by uricase, catalase and aldehyde dehydrogenase for determination of the uric acid concentration was evaluated for human serum and urine samples. More than 60 substances were tested for possible interferences. Alcohol dehydrogenase, formaldehyde and homogentisic acid can disturb the proposed assay, but at concentrations which are not usually encountered in human serum or urine. In the presence of protein at least 99% of the uric acid was recovered.

The effect of some analogues of disulfiram on the aldehyde dehydrogenases of sheep liver.

Abstract: The effect of some close structural analogues of disulfiram on the activity of the cytoplasmic and mitochondrial aldehyde dehydrogenases of sheep liver was studied Several thiuram disulphides are equally potent inhibitors of the cytoplasmic enzyme, but in all cases the mitochondrial enzyme is much less strongly affected Tetramethylthiuram monosulphide decreases the activity of the cytoplasmic enzyme in a process apparently involving a covalent interaction

Studies on the selective action of cyclophosphamide (NSC-26271): Inactivation of the hydroxylated metabolite by tissue-soluble enzymes.

Abstract: The hypothesis that selective action of cyclophosphamide, compared to other nitrogen mustards, is due to a balance between enzymatic formation of inactive metabolites and chemical formation of the alkylating product was studied in view of previous observation in our laboratory. Metabolite analysis, inhibition of growth of tumor cells in culture, and kinetic analysis of relevant enzyme activities were used in this investigation. The effect of tissue-soluble enzyme fractions on biochemically prepared aldophosphamide, aldophosphamide analogs, and phosphoramide mustard showed: (a) a range of deactivation abilities with aldophosphamide (liver greater than kidney greater than intestinal mucosa greater than tumor greater than spleen = bovine serum albumin solution); (b) the formation of different amounts of carboxyphosphamide from aldophosphamide; and (c) only comparatively small reductions in the toxicity of phosphoramide mustard and of 4-hydroxy-4methylcyclophosphamide. Correlations were found between NAD+-dependent aldehyde dehydrogenase activity and the deactivation ability of tissue-soluble enzyme fractions. Blockage (by C4 substitution) or inhibition (by disulfiram) of secondary oxidation of aldophosphamide, mediated by aldehyde dehydrogenase, resulted in diminished deactivation ability in vitro and reduced selectivity in vivo.

Transfer of the 1-pro-R and the 1-pro-S hydrogen atoms of ethanol in metabolic reductions in vivo.

Abstract: The transfer of deuterium from [1 R-2H]ethanol and [1 S-2H]-ethanol to reduced metabolites of administered compounds was measured in female rats provided with bile fistulas Administered cyclohexanone was reduced to cyclohexanol, and in this reduction hydrogen was transferred only from the 1-pro-R position of the ethanol The deuterium content in the cyclohexanol was about 67% of that in the ethanol In the reduction of the 17-oxo group in 3beta-hydroxy-5alpha-androstan-17-one, hydrogen was transferred both from the 1-pro-R position and the 1-pro-S position, resulting in degrees of labelling that were about 25% and 2%, respectively, of those in the specific positions of the ethanols The 1-pro-R and 1-pro-S positions of ethanol contributed about 9% and 5%, respectively, of the 3beta hydrogen in lithocholic acid formed from 3-oxo-5beta-cholanoic acid The results indicate that alcohol dehydrogenase and aldehyde dehydrogenase do not share a common pool of NAD, and that NADH formed during acetaldehyde oxidation is utilized for reductions in the cytosol to a smaller extent than the NADH formed in the alcohol dehydrogenase reaction This result supports the concept that aldehyde oxidation is mainly an intramitochondrial process The relatively extensive utilization of the 1-pro-S hydrogen of ethanol in the reduction of 3-oxo-5beta-cholanoic acid, that is probably NADPH-dependent, indicates that cytosolic NADPH may be produced from malate or isocitrate formed intramitochondrially

Intracellular Localization and Characterization of Beef Liver Aldehyde Dehydrogenase Isozymes

Abstract: Various physiological roles of mammalian aldehyde dehydrogenase had been anticipated because of its broad substrate specificity. In order to clarify roles of the enzyme and the regulation of aldehyde metabolisms in liver, the intracellular distribution and isozyme of beef liver aldehyde dehydrogenase were studied.The presence of the mitochondrial, the microsomal and the cytoplasmic isozymes were proved by the isoelectric focusing. These isozymes were different from each other in pH-activity curve in the responces for steroid hormones and disulfiram.It was suggested by comparing the reactivities of these isozymes for various aldehydes that particular aldehyde might be oxidized by a favorite isozyme at particular locality in the liver cells and that a share of physiological role among these isozymes is probable.

Metabolism of endogenous noradrenaline

Abstract: Publisher Summary This chapter describes the metabolism of endogenous noradrenaline. The metabolism of noradrenaline is carried out mainly by two enzymes, monoamine oxidase, and catechol- O -methyltransferase. Two additional enzymes are involved in either the reduction or the oxidation of the aldehyde of NA, which is formed through the activity of MAO. These enzymes include aldehyde reductase, which is a MADPH-dependent enzyme and aldehyde dehydrogenase, which is a NAD + -dependent enzyme. It is found that when transmitter release is elicited by nerve stimulation, a significant fraction of the NA released is collected as metabolites. It is found that for the nerve-muscle preparation of the cat nictitating membrane, 3 H-DOPEG is the main fraction in the overflow of 3 H transmitter elicited by nerve stimulation, accounting for approximately 40% of the total radioactivity. Under these experimental conditions, 3 H-NMN accounted for 20% of the total radioactivity released by nerve stimulation. Similar results were obtained in the perfused cat spleen. Under conditions of release elicited by nerve stimulation, the HDOPEG formed results from neuronal re-uptake of the released transmitter and subsequent presynaptic metabolism by MAO and aldehyde reductase.

Rates of induction of mitochondrial aldehyde dehydrogenase in rat liver.

Abstract: Aldehyde dehydrogenase activities in liver mitochondria isolated from rats given ethanol at hourly intervals by gastric intubation showed a brief lag period followed by a rapid increase in specific activities until a maximum was attained at about 3h.

New aldehyde dehydrogenase isozymes in chemically induced liver tumors in the rat.

Abstract: All liver tumors induced in rats by acetylaminofluorene (AAF) or dimethylaminoazobenzene (DAB), but only one out of 29 tumors induced by ethionine, exhibited new isozymes of aldehyde dehydrogenase. These new isozymes, which differed from those of normal liver with regard to activity, pI, stability, cellular distribution, and coenzyme specificity, were not found in fetal or regenerating rat liver, nor in spontaneous liver tumors of the mouse or mastomys, nor in several other tumors appearing in rats bearing AAF-induced liver tumors, nor in any of several transplanted Morris hepatomas. The activity of the new isozymes did not correlate with histological criteria of differentiation, and the new forms were sometimes detectable in the liver of AAF-fed rats in areas where no tumor was macroscopically or histologically visible.

Regulation of enzymes of ethanol metabolism in yeast (Rhodotorula gracilis).

Abstract: The three enzymes of ethanol metabolism alcohol dehydrogenase, aldehyde dehydrogenase and acetyl-CoA synthetase in the obligate aerobic yeastRhodotorula gracilis are repressed by glucose and induced by C2 metabolic fuels with a regulatory pattern indicating a correlation in the control mechanisms. To try an identification of the molecular signals involved in the transmission of the inducing stimulus, experiments were carried out by blocking with 2 mM pyrazole the ethanol ↼ ↼ acetaldehyde metabolic step. Results indicate that ethanol is not specifically required as a molecular signal for induction.

A New Enzymatic Determination of Cholesterol. The Use of Aldehyde Dehydrogenase to Measure H2O2 Producing Reactions, II.

Abstract: Cholesterol oxidase, coupled with the catalase and aldehyde dehydrogenase, is proposed for the determination of cholesterol. The main advantages of this procedure over comparable methods employing cholesterol oxidase are its short reaction time and the use of NADP which permits the direct calculation of the cholesterol concentration from the absorbance value.