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PubMed2003

Acetaldehyde alters Ca2+-release channel gating and muscle contraction in a dose-dependent manner.

We studied whether acetaldehyde, which is produced by alcohol consumption, impacts ryanodine receptor (RyR) activity and muscle force. Exposure to approximately 50-200 microM acetaldehyde enhanced channel activity of frog RyR and rabbit RyR1 incorporated into lipid bilayers. An increase in acetaldehyde to 1 mM modified channel activity in a time-dependent manner, with a brief activation and then inhibition. Application of 200 microM acetaldehyde to frog fibers increased twitch tension. The maximum rate of rise of tetanus tension was accelerated to 1.5 and 1.74 times the control rate on exposure of fibers to 50 and 200 microM acetaldehyde, respectively. Fluorescence monitoring with fluo 3 demonstrated that 200-400 microM acetaldehyde induced Ca(2+) release from the sarcoplasmic reticulum (SR) in frog muscles. Acetaldehyde at 1 mM inhibited twitch tension by approximately 12%, with an increased relaxation time after a small, transient twitch potentiation. These results suggest that moderate concentrations of acetaldehyde can elicit Ca(2+) release from the SR by increasing the open probability of the RyR channel, resulting in increased tension. However, the effects of acetaldehyde at clinical doses (1-30 microM) are unlikely to mediate alcohol-induced acute muscle dysfunction.

Acetaldehyde↗
PubMed2001

Role of protein tyrosine phosphorylation in acetaldehyde-induced disruption of epithelial tight junctions.

Acetaldehyde-induced cytotoxicity is an important factor in pathogenesis of alcohol-related diseases; however, the mechanism of this toxicity is unknown. We recently showed that acetaldehyde increases epithelial paracellular permeability. We asked whether protein tyrosine phosphorylation via modulation of tyrosine kinases and/or PTPases is a mechanism involved in acetaldehyde-induced disruption of the tight junctions in the Caco-2 cell monolayer. Immunofluorescence localization of occludin and ZO-1 showed disruption of the tight junctions in acetaldehyde-treated cell monolayer. Administration of genistein prevented acetaldehyde-induced permeability. Acetaldehyde increased tyrosine phosphorylation of three clusters of proteins with molecular masses of 30-50, 60-90, and 110-150 kDa; three of these proteins were ZO-1, E-cadherin, and beta-catenin. Acetaldehyde reduced PTPase activity in plasma membrane and soluble fractions, whereas tyrosine kinase activity remained unaffected. Treatment with acetaldehyde resulted in a 97% loss of protein tyrosine phosphatase (PTP)1B activity and a partial reduction of PTP1C and PTP1D activities. These results strongly suggest that acetaldehyde inhibits PTPases to increase protein tyrosine phosphorylation, which may result in disruption of the tight junctions.

Acetaldehyde↗
PubMed1989

Disposition of ethanol and acetaldehyde in late pregnant rats and their fetuses.

The pattern of ethanol and acetaldehyde appearance in blood after an oral ethanol gavage (4 g/kg body wt) was not different at 12 or 21 days' gestation compared to virgin rats. Five min after maternal ethanol administration, concentrations of ethanol in fetal blood were lower than in maternal blood; however, at 15 min after ethanol administration, fetal and maternal blood levels were similar. Ethanol concentrations in fetal blood and amniotic fluid were already at equilibrium 5 min after ethanol administration. Acetaldehyde concentrations in fetal blood and in amniotic fluid were undetectable at all the times investigated, with the exception of fetuses from two pregnant rats studied 3 h after ethanol administration. Alcohol dehydrogenase activity in fetal liver and in placenta at late pregnancy was very low or undetectable, suggesting a very low rate of ethanol oxidation in vivo. After intravenous administration of acetaldehyde (10 mg/kg body wt), blood acetaldehyde concentrations were higher in pregnant than in virgin rats. Acetaldehyde concentrations in fetal blood and in amniotic fluid were similar to maternal blood at 2, 5, and 30 min after injection. When circulating concentrations of maternal and fetal acetaldehyde, obtained after either ethanol or acetaldehyde administration, were plotted, it was found that fetal blood concentrations of acetaldehyde were only detectable when maternal blood concentrations were greater than 80 microM. Concerning the acetaldehyde oxidation capacity, both the high and low affinity components of aldehyde dehydrogenase activity in fetal liver and placenta were very low as compared with maternal liver. However, aldehyde dehydrogenase activity in fetal liver was much higher than in placenta.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1985

Effects of diethyldithiocarbamate, a metabolite of disulfiram, on the pharmacokinetics of alcohol and acetaldehyde in the rat.

The effects of diethyldithiocarbamate (DDC), a metabolite of disulfiram which is known as Antabuse, on the blood concentrations of alcohol and acetaldehyde were determined simultaneously by head space gas chromatography in rats. After an intravenous injection of alcohol, the blood concentration of acetaldehyde was much lower than that of the alcohol. A pharmacokinetic model featuring the liver compartment for acetaldehyde was used to estimate pharmacokinetic parameters on the assumption that the distribution volumes of the central compartments were same for alcohol and acetaldehyde, and that the elimination rate of acetaldehyde from liver was large enough to isolate the liver compartment from the central compartment. The results showed that the clearance of alcohol was 0.0226 l/min/kg and the elimination rate constant of acetaldehyde from the liver compartment was very large and 35 min-1. The administration of DDC decreased the above significantly to 0.0132 l/min/kg and 20 min-1, respectively. After intravenous infusion of acetaldehyde, the time course of the blood concentration of acetaldehyde was analyzed by the one compartment model. The estimated elimination rate constants from blood and the distribution volume were in good agreement with those calculated from alcohol injection, indicating the appropriateness of the method used in this study. DDC had no effect on the elimination of infused acetaldehyde from blood indicating that the elimination may be due to the loss from lungs into breath, from skin surfaces and/or from the kidney but not by metabolism in the liver.

Acetaldehyde↗
PubMed2000

Effects of acetaldehyde on responses of rabbit corpus cavernosal smooth muscle.

Ethanol has various effects on male sexual activity under the influence of direct and indirect, in acute and chronic alcohol ingestion. However, whether acetaldehyde, a principal metabolite of ethanol, may affect penile erection directly has still not been elucidated. This present study was, therefore, designed to clarify the pharmacologic effects of the acetaldehyde on corpus cavernosal smooth muscle. Corpus cavernosal strips were prepared from rabbit penises. Isometric tension changes of rabbit corpus cavernosal strips to various drugs and electrical field stimulation (EFS) in an organ chamber were recorded with a pressure transducer after active muscle tone had been induced by phenylephrine (10(-5) mol/L). At the concentrations employed, acetaldehyde had no effect on the pH of the bathing medium. Acetaldehyde in each concentration did not significantly affect resting tone of the smooth muscle during 30 min incubation. Acetaldehyde suppressed contractility induced by phenylephrine and KCI at 10(-4) mol/L, and relaxation induced by EFS and bethanechol at 10(-3) mol/L and 10(-4) mol/L respectively, but acetaldehyde enhanced relaxation induced by ATP at high acetaldehyde level. Sodium nitroprusside-induced relaxation was not affected at any employed acetaldehyde concentration. This suggests that increasing the acetaldehyde level may contribute to male erectile dysfunction mainly by the inhibition of nitric oxide formation.

Acetaldehyde↗
PubMed2001

Does acetaldehyde mediate ethanol action in the central nervous system?

BACKGROUND: Some of the effects of ethanol in the central nervous system are due to changes in function of ligand-gated ion channels. Production of detectable amounts of acetaldehyde, a primary metabolite of ethanol, has been demonstrated in brain homogenates. The aim of this study was to determine whether central actions that are often attributed to ethanol may actually be mediated by acetaldehyde. METHODS: The effects of acetaldehyde (1-1000 microM) were tested by two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes expressing 10 different ligand-gated ion channel receptors [alpha1 glycine; alpha1beta2gamma2Sgamma-aminobutyric acid (GABA)A; rho1 GABAc; 5-hydroxytryptamine-3A; NR1a/NR2A NMDA; GluR1/GluR2 AMPA; GluR6/KA2 kainate; and alpha4beta2, alpha4beta4, and alpha2beta4 nicotinic-acetylcholine] and the G-protein-coupled inward rectifying potassium channel GIRK2. We also investigated the effect of acetaldehyde on the dopamine transporter (DAT), performing dopamine uptake assays in oocytes expressing DAT. RESULTS: Acetaldehyde (1 and 10 microM) significantly enhanced alpha1 glycine receptor-mediated currents. Acetaldehyde did not affect the function of any of the other receptors tested or the potassium currents measured in GIRK2 channels. Moreover, acetaldehyde did not alter the DAT-mediated dopamine uptake. CONCLUSIONS: Our results suggest a potential minor role for acetaldehyde in the glycine receptor-mediated effects of ethanol. Otherwise, acetaldehyde does not modulate function of the neuronal receptors tested in this study, in GIRK channels or DAT, when expressed recombinantly in Xenopus laevis oocytes.

Acetaldehyde↗
PubMed2001

Assays for acetaldehyde-derived adducts in blood proteins based on antibodies against acetaldehyde/lipoprotein condensates.

BACKGROUND: Acetaldehyde-derived protein condensates (adducts) have been suggested as promising biological markers of alcohol abuse because they represent actual metabolites of ethanol. However, the detection of such condensates in vivo has been hampered by a lack of sensitive and specific methods. METHODS: To develop new approaches for the detection of acetaldehyde adducts, we have raised antibodies against condensates with acetaldehyde and lipoproteins, which have previously been shown to be readily modified by acetaldehyde in vitro. The characteristics of these antibodies were compared with those raised against bovine serum albumin/acetaldehyde adduct and against other types of lipoprotein modifications, as induced by malondialdehyde, oxidation, and acetylation. RESULTS: The antibodies raised against low-density lipoprotein (LDL)/acetaldehyde, very low density lipoprotein (VLDL)/acetaldehyde, and bovine serum albumin/acetaldehyde all reacted with protein adducts generated at physiologically relevant concentrations of acetaldehyde in vitro, whereas the antibodies raised against malondialdehyde/LDL, oxidized LDL, or acetylated LDL were not found to cross-react with the acetaldehyde-derived adducts. In assays for acetaldehyde adducts from erythrocyte and serum proteins of patients with excessive ethanol consumption (n = 32) and healthy control individuals (n = 22), the antibody prepared against the acetaldehyde/VLDL condensate was found to provide the most effective detection of acetaldehyde adducts in vivo. CONCLUSIONS: Current data indicate that acetaldehyde generates immunogenic adducts with lipoproteins in vivo. Antibodies raised against the VLDL/acetaldehyde may provide a basis for new diagnostic assays to examine excessive alcohol consumption.

Acetaldehyde↗
PubMed1991

Acetaldehyde increases procollagen type I and fibronectin gene transcription in cultured rat fat-storing cells through a protein synthesis-dependent mechanism.

We previously reported that acetaldehyde increases the production of type I collagen in cultured rat fat-storing cells. We studied the regulation of this effect by determining the expression of procollagen type I, fibronectin and transforming growth factor-beta 1 messenger RNAs in passage 1 and 2 cultures of fat-storing cells exposed to acetaldehyde for up to 24 hr. By 6 hr, acetaldehyde increased the steady-state levels of alpha 1 procollagen type I messenger RNA 3.2-fold and of fibronectin messenger RNA 2.8-fold above control values. At 24 hr, messenger RNA levels remained elevated. In contrast, transforming growth factor-beta 1 messenger RNA steady-state levels remained unaltered by 6 hr, but increased 1.5-fold by 24 hr. Cycloheximide (0.3 mmol/L) completely inhibited the acetaldehyde effect when added at zero time but was less effective when added at 15 min. The effect of acetaldehyde was not modified when cells were cultured in the presence of the acetaldehyde dehydrogenase inhibitor cyanamide (100 mumol/L). Fat-storing cells were also cultured in the presence of lactate (5, 15 and 25 mmol/L) for 6 hr. At none of these concentrations was any effect seen on either alpha 1(I) procollagen or fibronectin messenger RNAs. In the presence of methylene blue, a scavenger of reducing equivalents, the effect of acetaldehyde on alpha 1(I) procollagen and fibronectin gene expression was totally inhibited. Transcription run-on assay showed that acetaldehyde increased both procollagen type I and fibronectin transcriptional activity threefold and 2.5-fold, respectively. We conclude that acetaldehyde increases alpha 1(I) procollagen and fibronectin gene expression through enhanced transcription by a mechanism dependent on newly synthesized proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1990

delta-Aminolevulinic acid dehydratase in rat liver: studies on the effects of ethanol, acetaldehyde, and B6 vitamers.

Because ethanol ingestion lowers delta-aminolevulinic acid dehydratase (ALAD) activity in liver and red cells, effects of ethanol and acetaldehyde on ALAD in rat liver cytosol were studied. When added to the assay mix, as little as 0.5 mmol/L acetaldehyde competitively inhibited ALAD even in the presence of dithiothreitol, a sulfhydryl reagent. ALAD activity also fell when undiluted cytosol was incubated at 37 degrees with as little as 0.25 mmol/L acetaldehyde for 8 hours before enzyme assay. Inactivation of ALAD by acetaldehyde was prevented by the metabolic inhibitor NaF but not by the aldehyde dehydrogenase inhibitor cyanamide. Incubation of undiluted cytosol with 20 mmol/L ethanol also decreased ALAD activity, but addition of ethanol to the assay mix had no effect. Ethanol-mediated inactivation of ALAD was reduced by inhibition of alcohol dehydrogenase with 4-methylpyrazole, but ALAD activity was not decreased by incubation of undiluted cytosol with acetate or sorbitol or by addition of acetate to the assay mix. The aldehydic B6 vitamers, pyridoxal and pyridoxal phosphate, also inhibited ALAD activity when added to the assay mix. However, these vitamers increased ALAD activity and decreased acetaldehyde-mediated inactivation of ALAD when incubated for 8 hours with undiluted cytosol. We conclude that (1) acetaldehyde decreases ALAD activity both by competitive inhibition with substrate and by inactivation of enzyme protein and that (2) inactivation of ALAD by acetaldehyde may require nonoxidative metabolism of acetaldehyde. The net pharmacologic effect of B6 vitamers on ALAD activity and on inactivation of ALAD by acetaldehyde remains to be determined.

Acetaldehyde↗
PubMed1979

A comparison of the effects of ethanol and acetaldehyde on glucose production from various precursors by isolated rat liver cells.

A comparison of the actions of ethanol and acetaldehyde on glucose production from various precursors by isolated rate liver cells was made to evaluate the role of acetaldehyde in the effects of ethanol. Both ethanol and acetaldehyde stimulated glucose production from pyruvate, inhibited glucose production from glycerol, xylitol, and sorbitol, and both had no effect with fructose. Ethanol, but not acetaldehyde, inhibited glucose production from lactate, dihydroxyacetone and alanine. The inhibitory effects of ethanol and acetaldehyde were prevented by methylene blue, an aritificial electron acceptor. The similarities in the actions of ethanol and acetaldehyde on glucose production from some substrates, e.g. pyruvate, glycerol, xylitol and sorbitol suggest that the metabolism of acetaldehyde may contribute to the effects of ethanol on gluconeogenesis from these substrates. Differences in the actions of ethanol and acetaldehyde on glucose production from other substrates reflect the different compartments, cytosol for ethanol, mitochondrial for acetaldehyde, in which these compounds are metabolized in the liver.

Acetaldehyde↗
PubMed1993

Problems involved in the determination of endogenous acetaldehyde in human blood.

Little is known about the possible existence of endogenous acetaldehyde in human blood. This has partly been due to analytical difficulties preventing accurate determination of blood acetaldehyde levels with and without the presence of ethanol. In the present study the possible existence of endogenous acetaldehyde in human blood was investigated with headspace gas chromatography using three different procedures for the treatment of samples: (1) no treatment of whole blood, cells, or plasma (direct headspace method), (2) hemolysation, and (3) perchloric acid (PCA) precipitation, prior to the headspace determinations. In in vitro experiments, with the direct headspace and the hemolysation methods, higher acetaldehyde peaks were obtained depending on the headspace incubation time, temperature and ethanol concentration. Both methods displayed about the same values of acetaldehyde in blood cells, ranging between 0 and 40 microM, at incubation times between 15 and 180 min, an incubation temperature of 65 degrees C, and ethanol concentrations less than 5 microM. Less acetaldehyde formation (0-15 microM) was obtained with PCA precipitates of whole blood and cell components. Very low acetaldehyde levels (0-1 microM) were obtained in the supernatants without precipitates from either whole blood or cells after headspace equilibration. Substantially less acetaldehyde was formed in plasma preparations than with whole blood and cell fractions. In human experiments, the disturbance of endogenous or exogenous ethanol was minimized by separating and washing the blood cells followed by PCA treatment. No differences in acetaldehyde concentrations were observed in blood samples taken before, during, or after ethanol intoxication (1.5 g/kg dose) of four healthy non-alcoholic volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1997

Acetaldehyde as well as ethanol is metabolized by human CYP2E1.

Acetaldehyde was oxidized by rat and human hepatic microsomes in the presence of NADPH. We designated this NADPH-dependent oxidation system MAOS (microsomal acetaldehyde-oxidizing system), to distinguish it from the NAD-dependent acetaldehyde oxidation system of acetaldehyde dehydrogenase in mitochondria and cytosol. This activity was increased 2.3-fold by giving rats ethanol. Judging from the Vmax/Km values, the metabolic capacity of rat hepatic microsomes for MAOS activity was increased 24-fold by ethanol. The acetaldehyde oxidation activity of eight forms of purified rat cytochrome P450 was investigated in a reconstituted system. CYP2E1 had the highest level, followed by CYP1A2 and 4A2. Immunoinhibition studies showed that an anti-CYP2E1 antibody inhibited 90% of the MAOS activity in rats given ethanol. NADPH-dependent acetate formation was 12% or 33.6% of the NAD-dependent acetate formation in liver homogenates of control rats and those treated with ethanol, respectively. We investigated human MAOS activity further. Among the 10 forms of human cytochrome P450 expressed in yeast, CYP2E1 had especially high acetaldehyde oxidation activity. The correlation of MAOS activity with the levels of immunoreactive CYP2E1 in individual human microsomes was highly significant (r2 = 0.88, P < .01). These results indicate that hepatic CYP2E1 mainly contributes to MAOS in rats and humans, the pathway of which may play an alternative role against acetaldehyde in the liver after alcohol consumption together with acetaldehyde dehydrogenase in the metabolism of acetaldehyde.

Acetaldehyde↗
PubMed1998

Role of catalase in in vitro acetaldehyde formation by human colonic contents.

Ingested ethanol is transported to the colon via blood circulation, and intracolonic ethanol levels are equal to those of the blood ethanol levels. In the large intestine, ethanol is oxidized by colonic bacteria, and this can lead to extraordinarily high acetaldehyde levels that might be responsible, in part, for ethanol-associated carcinogenicity and gastrointestinal symptoms. It is believed that bacterial acetaldehyde formation is mediated via microbial alcohol dehydrogenases (ADHs). However, almost all cytochrome-containing aerobic and facultative anaerobic bacteria possess catalase activity, and catalase can, in the presence of hydrogen peroxide (H2O2), use several alcohols (e.g., ethanol) as substrates and convert them to their corresponding aldehydes. In this study we demonstrate acetaldehyde production from ethanol in vitro by colonic contents in a reaction catalyzed by both bacterial ADH and catalase. The amount of acetaldehyde produced by the human colonic contents was proportional to the ethanol concentration, the amount of colonic contents, and the length of incubation time, even in the absence of added nicotinamide adenine dinucleotide or H2O2. The catalase inhibitors sodium azide and 3-amino-1,2,4-triazole (3-AT) markedly reduced the amount of acetaldehyde produced from 22 mM ethanol in a concentration dependent manner compared with the control samples (0.1 mM sodium azide to 73% and 10 mM 3-AT to 67% of control). H2O2 generating system [beta-D(+)-glucose + glucose oxidase] and nicotinamide adenine dinucleotide induced acetaldehyde formation up to 6- and 5-fold, respectively, and together these increased acetaldehyde formation up to 11-fold. The mean supernatant catalase activity was 0.53+/-0.1 micromol/min/mg protein after the addition of 10 mM H2O2, and there was a significant (p < 0.05) correlation between catalase activity and acetaldehyde production after the addition of the hydrogen peroxide generating system. Our results demonstrate that colonic contents possess catalase activity, which probably is of bacterial origin, and indicate that in addition to ADH, part of the acetaldehyde produced in the large intestine during ethanol metabolism can be catalase dependent.

Acetaldehyde↗
PubMed1993

Zonal distribution of protein-acetaldehyde adducts in the liver of rats fed alcohol for long periods.

Acetaldehyde, a highly reactive intermediate of alcohol metabolism, has been shown to form adducts with liver proteins in rats fed alcohol for long periods. In this report, the zonal distribution of liver protein-acetaldehyde adducts that formed in vivo was studied by means of histoimmunostaining. Rats were pair-fed alcohol-containing and alcohol-free AIN'76 liquid diets for 2 or 11 wk before they were killed and subjected to whole body perfusion with paraformaldehyde. Each liver was cut into 60-microns-thick slices. Slices were first treated with 10% hydrogen peroxide to eliminate endogenous peroxidase activity. They were then incubated sequentially with rabbit antihemocyanin-acetaldehyde adduct, goat antirabbit serum IgG and rabbit peroxidase-antiperoxidase complex. The liver slices were stained with diaminobenzidine and counterstained with methylgreen. In the livers of rats fed alcohol for 2 wk, peroxidase activity was evident in the perivenous zone but not the periportal zone. No staining was obtained when the primary antibody had been preabsorbed with immobilized hemocyanin-acetaldehyde adduct or if the liver slices were incubated with the unimmunized rabbit IgG. Slight staining of the perivenous zone was seen in the livers of control rats, presumably because of minimal protein-acetaldehyde adduct formation emanating from endogenous acetaldehyde. When rats were fed alcohol for longer periods (e.g., 11 wk), protein-acetaldehyde adducts were still seen predominantly in the perivenous zone, but the distribution pattern was more diffuse than that observed in the livers of rats fed alcohol for only 2 wk. More liver cells produced protein-acetaldehyde adducts when rats were fed the alcohol-containing diet supplemented with cyanamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1985

Effects of ethanol and acetaldehyde on phagocytic functions.

Although a number of skin diseases are characterized by the presence of an increased number of phagocytes in their lesions, the effects of alcohol on phagocytic functions are not clearly understood. Therefore, we measured the influence of ethanol and acetaldehyde on the generation of oxygen radicals, chemotaxis and the release of lysosomal enzymes from human phagocytes. We added 0.03%-3% ethanol and 0.005%-0.25% acetaldehyde to cell cultures. We found that both ethanol and acetaldehyde suppressed the generation of oxygen radicals from granulocytes and monocytes; the ID50 was achieved at concentrations of approximately 0.25% for ethanol and 0.03% for acetaldehyde. A significant inhibition of granulocyte chemotaxis was first noted with 0.063% ethanol and 0.016% acetaldehyde. Ethanol and acetaldehyde inhibited the release of the lysozyme of monocytes at concentrations of greater than 0.75% and greater than 0.03% respectively, but granulocytes were unaffected; the release of beta-glucuronidase and lactate dehydrogenase remained stable. Due to the high volatility of the agents, especially acetaldehyde, under the experimental procedures employed, the actual concentrations of the agents were probably lower and similar to those measured in vivo. Our results indicate that defined phagocytic functions are strongly inhibited by concentrations of ethanol and acetaldehyde which are associated with moderate to severe inebriation.

Acetaldehyde↗
PubMed2003

Acetaldehyde adducts in the brain of alcoholics.

Acetaldehyde binds to some proteins and becomes a Schiff base. It is assumed that after the consumption of ethanol the acetaldehyde binds to the proteins to form adducts, and such acetaldehyde adducts are associated with organ diseases. We investigated the detection of acetaldehyde adducts in the brain region of a human alcoholics. Brain samples collected from an alcoholic autopsied case were used. Determination of acetaldehyde adducts was performed using a fluorescence immmunohistochemical staining method with antibodies against acetaldehyde adducts. We demonstrated acetaldehyde adducts in the frontal cortex and the midbrain of an alcoholics. Our studies showed that an acetaldehyde adduct was produced in the brain of alcoholics.

Acetaldehyde↗
PubMed1987

Oxidation product(s) in acetaldehyde reacts with NAD(P)H and interferes with assay of alcohol dehydrogenase.

A decrease in absorbance at 340 nm, at rates similar to those obtained with alcohol dehydrogenases in routine assays, occurred when NADH or NADPH was mixed with acetaldehyde that had been exposed to air for various durations. NAD(P)H was apparently oxidized by interfering substance(s) present in acetaldehyde. Reagent-grade acetaldehyde from newly opened bottles as well as acetaldehyde redistilled under strictly O2-free conditions contained minimal amounts of NAD(P)H-reacting substance(s). Redistillation under poor anaerobic conditions or in air increased the amount of NAD(P)H-reacting substance(s) in redistilled acetaldehyde. NADPH reacted at a higher rate than NADH with the interfering substance(s) in Tris-Cl buffer at pH 7.5. Also, the reaction was faster in Tris buffer than in phosphate buffer at pH 7.5. The NAD(P)H-oxidizing reaction may not be apparent when the nominal concentration of acetaldehyde used was below 5 mM, but the measured ethanol dehydrogenase activity could be significantly lower with acetaldehyde containing a measurable level of interfering substance(s). This study suggests that acetaldehyde is most easily tested with NADPH for the presence of a significant level of interfering substance(s) and that redistillation, if necessary, must be performed under strictly O2-free conditions.

Acetaldehyde↗
PubMed1992

Substoichiometric inhibition of microtubule formation by acetaldehyde-tubulin adducts.

We have shown previously that acetaldehyde forms stable covalent adducts with tubulin, resulting in impaired microtubule formation. The present study explored the mechanism responsible for impaired microtubule formation caused by the substoichiometric stable binding of acetaldehyde to tubulin. The free tubulin dimer was much more reactive with acetaldehyde than microtubules, binding more than twice as much aldehyde. The dimer also formed nearly twice as many stable adducts on its alpha-chain as on its beta-chain, whereas microtubules exhibited an equal distribution of adducts between the two subunits. These data confirm that the alpha-chain of free tubulin, but not microtubules, has an accessible highly reactive lysine (HRL) residue that is a preferential target of acetaldehyde binding. Adduct formation with the HRL residue also correlated with impaired tubulin polymerization, and only 0.08 moles of acetaldehyde bound per mole of HRL was required for complete inhibition; however, adducts with other lysine residues (bulk adducts) did not affect assembly. Adducts to microtubule-associated proteins (MAPs) also impaired the assembly of tubulin, but were much less effective than HRL adducts. In a copolymerization assay, HRL-adducted tubulin, in addition to being itself assembly incompetent, also interfered with polymerization of normal (unadducted) tubulin. Bulk adducts did not alter assembly and were incorporated normally into the growing polymer. When tubulin was cleaved by the proteolytic enzyme, subtilisin, microtubule formation could readily take place in the absence of MAPs. In this polymerization system, HRL adducts, but not bulk adducts, still markedly inhibited assembly. When low concentrations of acetaldehyde (50 microM) were used to generate HRL adducts, an adduct on only 1 out of 20 tubulin molecules was sufficient to totally block polymerization. These findings indicate that substoichiometric amounts of acetaldehyde bound to HRL of tubulin can markedly inhibit microtubule formation via direct interference of dimer-dimer interactions, and further suggest that low concentrations of acetaldehyde could generate sufficient amounts of HRL adducts in cellular systems to alter microtubule formation and function.

Acetaldehyde↗