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O Tottmar

Publications and source records attributed to O Tottmar.

48 records · Page 3Linked to original sources
PubMed1979

Blood pressure response to ethanol in relation to acetaldehyde levels and dopamine-beta-hydroxylase activity in rats pretreated with disulfiram, cyanamide and coprine.

The blood pressure response after ethanol administration was studied in relation to blood acetaldehyde levels, aldehyde-dehydrogenase (ALDH)--and dopamine-beta-hydroxylase (DBH) activities in rats pretreated with the ethanol-sensitizing compounds disulfiram, cyanamide and coprine and the DBH-inhibitor FLA-57. Disulfiram, cyanamide and coprine, but not FLA-57, inhibited the low-Km ALDH in the liver and caused an increased acetaldehyde level in blood. Disulfiram and FLA-57, but not cyanamide and coprine, decreased the DBH-activity in the heart and the levels of norepinephrine in the heart and the brain. In disulfiram-treated rats with a low DBH-activity, a fall in blood pressure was observed at acetaldehyde levels being slightly higher than those found in control rats. In disulfiram-treated rats with a DBH-activity close to control activity and in rats pretreated with cyanamide or coprine, a fall in blood pressure were observed in rats pretreated with FLA-57. In rats pretreated with coprine + FLA-57, the fall in blood pressure was similar, or even lower, than in rats pretreated with coprine alone. The results suggest that acetaldehyde is the main determinant of the hypotension elicited by ethanol in rats pretreated with ALDH-inhibitors, and that the role of DBH in the disulfiram-ethanol reaction has been over-estimated in previous studies.

Acetaldehyde↗
PubMed1978

Determination of acetaldehyde in rat blood by the use of rat liver aldehyde dehydrogenase.

A method has been developed for the determination of low concentrations of acetaldehyde in rat blood. The method involves extraction of blood in perchloric acid followed by a fluorimetric determination of acetaldehyde in neutralized extracts by the use of a low K(m) aldehyde dehydrogenase isolated from rat liver mitochondria. Acetaldehyde concentrations down to 2 to 3 microM could be detected in blood samples of 0.1 ml containing high concentrations of ethanol (10-40 mM). Due to its simplicity, sensitivity, and the use of a low-cost fluorimeter, this enzymatic method should be a valuable complement to gas chromatographic methods for acetaldehyde determination.

Acetaldehyde↗
PubMed1978

The presence of an aldehyde dehydrogenase inhibitor in animal diets and its effects on the experimental results in alcohol studies.

1. The effects of chronic ethanol administration on the metabolism of ethanol and acetaldehyde were studied in rats fed on a commercial diet containing an aldehyde dehydrogenase inhibitor, calcium cyanamide (calcium carbimide), as a contaminant in the calcinated bone-meal fraction of the diet. 2. Rats given an ethanol solution (150 ml/l) for 3 months and fed on a diet containing calcinated bone meal showed two times higher activity of the low-Km acetaldehyde dehydrogenase in the liver, 26% higher rate of ethanol elimination, and two to three times lower acetaldehyde levels in blood during ethanol elimination compared with control rats pair-fed on the same diet. 3. The results obtained from the ethanol-treated rats were similar to those obtained in experiments on control rats fed on diets not containing calcinated bone meal. 4. Experiments performed in vitro and in vivo on the inhibition of the acetaldehyde metabolism by cyanamide suggested that the apparent effects of chronic ethanol intake were really caused by calcium cyanamide in the diet.

Acetaldehyde↗
PubMed1978

A comparative study on the effects of disulfiram, cyanamide and 1-aminocyclopropanol on the acetaldehyde metabolism in rats.

1-aminocyclopropanol (ACP) is a potent inhibitor of aldehyde dehydrogenase (ALDH) in vivo and in vitro. Like cyanamide it has a rapid onset of action in vivo with the highest inhibition occurring after 2--24 hrs. and a long duration of action like disulfiram with measurable inhibition after 144 hrs. All the three inhibitors decreased the activity of the mitochondrial low-Km ALDH strongly in vivo, however, in markedly different doses. Cyanamide inhibited the high-Km ALDH only in vivo, whereas in vitro, the hihgh-Km ALDH was unaffected by cyanamide but significantly inhibited by disulfiram and ACP. The inhibition produced by the inhibitors appeared to be irreversible. Acetaldehyde protected the low-Km enzyme at different extents depending on the inhibitor used. The inhibition of ALDH in intoxicated and control rats and its relation to acetaldehyde oxidation and the disulfiram-ethanol reaction are discussed.

Acetaldehyde↗
PubMed1977

Effects on rat liver acetaldehyde dehydrogenases in vitro and in vivo by coprine, the disulfiram-like constituent of Coprinus atramentarius.

Coprine, the disulfiram-like constituent of the mushroom Coprinus atramentarius was found to inhibit the low-Km dehydrogenase in rat liver and to increase the acetaldehyde level in blood during ethanol metabolism in vivo. Coprine did not inhibit the low-Km enzyme in vitro, but the hydrolytic product of coprine, 1-aminocyclo-propanol, was a potent inhibitor both in vitro and in vivo. A rapid onset of inhibition was observed after administration of coprine and the inhibition was long-lasting. It is suggested that 1-aminocyclopropanol is responsible for the inhibition caused by coprine in vivo.

Acetaldehyde↗
PubMedDate not supplied

Assay of human blood aldehyde dehydrogenase activity by high-performance liquid chromatography.

A simple and sensitive method for routine analysis of aldehyde dehydrogenase (ALDH, EC 1.2.1.3) activity in human blood has been developed. The assays were performed by incubating diluted whole blood samples in sodium pyrophosphate buffer in the presence of NAD. The aldehyde derived from dopamine, or alternatively the aldehyde from serotonin, was used as the substrate and the acid formed was measured using high-performance liquid chromatography with electrochemical detection. The present method can be performed with a small sample (10-25 microliters) of whole blood and no time-consuming pretreatments of the samples are needed. Six to seven samples can be assayed per hour, and the precision of the method was 2%. For comparison, assays were also performed with two fluorimetric methods, one measuring the formation of indole-3-acetic acid from indole-3-acetaldehyde and the other measuring the rate of acetaldehyde disappearance.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Reactions of biogenic aldehydes with hemoglobin.

The aldehyde derivatives of dopamine and serotonin, 3,4-dihydroxyphenylacetaldehyde (DOPAL) and 5-hydroxyindole-3-acetaldehyde (5-HIAL), respectively, were incubated with human hemoglobin under physiological conditions. Both DOPAL and 5-HIAL, as well as dopamine, showed a time-dependent disappearance during the incubations, whereas this was not observed with serotonin. The amounts of free aldehydes recovered after incubation with hemoglobin, as analysed by high-performance liquid chromatography with electrochemical detection, corresponded to the amounts of acid metabolites formed in enzymatic assays, when the samples instead were incubated with aldehyde dehydrogenase. Incubations with DOPAL, 5-HIAL, or dopamine, and hemoglobin also resulted in distinct increases in the absorption spectra between 250-350 nm, whereas no similar increase was observed with serotonin. Addition of sodium borohydride to the incubates, which is used to stabilize Schiff base adducts between aldehydes and proteins, resulted in reduction of DOPAL and 5-HIAL to their corresponding alcohol metabolites. However, a rapid initial disappearance of the aldehydes, as analysed from the recoveries of the alcohol metabolites, was observed, followed by a more slow disappearance rate throughout the incubation period.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Application of a high performance liquid chromatography method for screening of aldehyde dehydrogenase isozyme deficiency in hair roots from different ethnic groups.

A sensitive high performance liquid chromatography method has been used to measure aldehyde dehydrogenase (ALDH) activity in hair roots from Caucasian and Japanese subjects. Kinetic studies confirmed previous isoelectric focusing results that hair roots from Caucasians have two forms of ALDH, one low Km form and another high Km form, while hair roots from Japanese individuals who show a flushing reaction after ethanol intake lack, or have low activity of, the low Km form. By taking the ratio of the activities measured at a low (3 microM) and a high (75 microM) concentration of the substrate (3,4-dihydroxyphenylacetaldehyde), a suitable index for ALDH deficiency was obtained. The ratio varied between 1.6 and 3.5 for Caucasians and between 7 and 23 for Japanese flushers, and it was 2.5 for a Japanese nonflusher. The current method allows a more quantitative and qualitative assessment of the ALDH isozyme pattern in hair roots than that obtained with the isoelectric focusing technique.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Cellular distribution and properties of human blood aldehyde dehydrogenase.

The activity of aldehyde dehydrogenase (ALDH, EC 1.2.1.3) was measured in different fractions of human blood. Of the recovered activity 99% was detected in the intracellular fraction of the erythrocytes. The results also indicated the presence of ALDH activity in the leukocytes, since an increased activity was obtained after cultivation of the cells in the presence of a mitogen. No activity was detected in platelets, plasma, or erythrocyte membranes. Nonlinear Lineweaver-Burk plots were obtained with acetaldehyde, 3,4-dihydroxyphenylacetaldehyde, and indole-3-acetaldehyde as the substrates. The apparent Km values, calculated from the low and high substrate concentration ranges of the curves, were much lower for 3,4-dihydroxyphenylacetaldehyde and indole-3-acetaldehyde than for acetaldehyde. Disulfiram caused almost complete inhibition of the blood ALDH activity in assays with acetaldehyde as the substrate, whereas 15-30% of the activity remained unaffected in assays with 3,4-dihydroxyphenylacetaldehyde and indole-3-acetaldehyde. Kinetic experiments using the mixed substrate method and isoelectric focusing of a partially purified sample of blood did not reveal the presence of more than one isozyme.

Aldehyde Dehydrogenase↗