Showing papers on "Aldehyde dehydrogenase published in 1983"
TL;DR: Normal Japanese subjects were divided into two groups, i.e., one with both low and high Km isozymes of aldehyde dehydrogenase for acetaldehyde and the other deficient in the low Km isozyme, and the frequency of deficient phenotype of ALDH in Japanese was presumed to be about 36%.
Abstract: Normal Japanese subjects were divided into two groups, ie, one with both low and high Km isozymes of aldehyde dehydrogenase for acetaldehyde, and the other deficient in the low Km isozyme After intake of 04 g/kg alcohol, the deficient subjects showed high level of blood acetaldehyde, facial flushing and the other dysphoric symptoms, including increase of pulse rate, decrease of diastolic blood pressure, changes of pulse wave in the fingertip, and elevation of the arterial pressure and blood flow rate in common carotid arteries as well as increase of plasma catecholamines level In contrast, subjects with normal ALDH did not show these changes From the observation of liver specimens obtained at autopsy, the frequency of deficient phenotype of ALDH in Japanese was presumed to be about 36%
163 citations
TL;DR: A higher frequency of individuals possessing lower ALDH activity in hemolysates was observed in alcoholics than that in controls, which indicates a possible protective role of ALDH isozymes against alcoholism.
Abstract: Aldehyde dehydrogenase (ALDH) isozyme composition in hair roots was determined using isoelectric focusing in 105 healthy individuals, 175 alcoholics, 86 schizophrenics and 47 drug dependents. The incidence of ALDH isozyme I deficiency in healthy populations in Japan was found to be about 40%. Among alcoholics, however, only 2.3% individuals had the isozyme deficiency. There was no difference between normal controls, schizophrenics and drug dependents regarding the incidence of ALDH isozyme I deficiency. These observations indicate a possible protective role of ALDH isozymes against alcoholism. The higher frequency of ALDH isozyme I deficiency in Japanese may explain why alcoholism in Japan has been less frequent than in European and North American countries. ALDH isozyme II was found in most of the tissues and erythrocytes. A higher frequency of individuals possessing lower ALDH activity in hoemolysates was observed in alcoholics than that in controls. The activity of acid phosphatse was also reduced in alcoholics. Alcohol abuse might result in distrubed protein synthesis in the erythrocytes.
100 citations
TL;DR: Data show that rat liver contains at least three ALDH enzymes which oxidize malondialdehyde, a difunctional three-carbon aldehyde thought to be toxic, which is generated during membrane lipid peroxidation in hepatocytes.
69 citations
TL;DR: The measurement of ALDH in erythrocyte lysates may offer yet another sensitive and specific biochemical marker of alcoholism.
Abstract: Human erythrocyte aldehyde dehydrogenase (ALDH, EC 1.2.1.3) shows a single activity band on starch gel electrophoresis and isoelectric focusing in polyacrylamide gel (pI = 5.0−5.3). The erythrocyte enzyme is identical with the slower migrating, disulfiram-sensitive human liver ALDH isozyme II. Significantly decreased activity of erythrocyte ALDH was observed in chronic alcoholics when compared with healthy controls and non-alcoholic psychiatric and gastrointestinal patients. The measurement of ALDH in erythrocyte lysates may offer yet another sensitive and specific biochemical marker of alcoholism.
51 citations
01 Jan 1983
TL;DR: It is demonstrated that the isozymes of ALDH may play an important role in the pathogenesis of alcohol-related organ damage and in the biological sensitivity to alcohol in certain ethnic groups.
Abstract: Isozymes of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were studied in human organs and tissues using sensitive analytical techniques. Both ADH and ALDH showed an extensive polymorphism among different racial groups. In liver extracts and other tissues of Japanese an isozyme of ALDH (ALDH I) with a low Km for acetaldehyde was found to be deficient. The ALDH isozyme deficiency might account for the marked initial sensitivity to alcohol in Orientals owing to their impaired acetaldehyde oxidizing capacity. Significantly low erythrocyte ALDH activity was noted more frequently in chronic alcoholics than in healthy controls. After subcellular fractionation of livers from alcoholics a preferential damage of mitochondrial ALDH isozyme was observed. The metabolism of acetaldehyde has received considerable attention in the past few years, owing to the toxic effects of this substance. Rapid progress has been made in the understanding of the multiple molecular forms of ADH and ALDH in human tissues. Our recent studies have demonstrated that the isozymes of ALDH may play an important role in the pathogenesis of alcohol-related organ damage and in the biological sensitivity to alcohol in certain ethnic groups. A possible protection of ALDH I deficiency against alcoholism in Japanese has been discussed. More recent reports [Imprain et al, 1982; Jones, 1982] indicate that, in addition to the enzymatically active ALDH II, tissues from Orientals deficient in ALDH I isozyme contain enzymatically inactive, immunologically cross-reactive material homologous with ALDH I. Thus, the absence of ALDH I isozyme is not due to a regulatory mutation, a gene deletion, or a nonsense mutation, but probably results from a structural mutation.(ABSTRACT TRUNCATED AT 250 WORDS)
48 citations
TL;DR: The results imply that in vivo disulfiram may act as an oxidation-reduction catalyst for the inactivation of aldehyde dehydrogenase.
Abstract: Stoicheiometric amounts of [14C]disulfiram react rapidly with sheep liver cytoplasmic aldehyde dehydrogenase to give loss of catalytic activity and incorporation of the expected amount of radioactivity. In a subsequent slower reaction the label is lost from the enzyme without re-emergence of enzymic activity. The results imply that in vivo disulfiram may act as an oxidation-reduction catalyst for the inactivation of aldehyde dehydrogenase.
45 citations
Journal Article•
TL;DR: A procedure for the histochemical localization of hepatic ALDH which has proven extremely useful as an additional probe for studying changes in this enzyme during hepatocarcinogenesis is developed.
Abstract: Significant changes in aldehyde dehydrogenase (ALDH) activity occur during chemically induced rat hepatocarcinogenesis. We have developed a procedure for the histochemical localization of hepatic ALDH which has proven extremely useful as an additional probe for studying changes in this enzyme during hepatocarcinogenesis. Frozen sections of fresh tissue were stained for ALDH using either propionaldehyde-NAD to detect normal liver ALDH or benzaldehyde-NADP to detect tumor ALDH. Histochemically, normal liver ALDH activity is strongly centrilobular with only slight periportal activity and produces a characteristic staining pattern. During hepatocarcinogenesis, ALDH staining patterns in grossly normal liver range from normal-appearing to patterns of distinct, intense focal hepatocyte staining with propionaldehyde-NAD and/or benzaldehyde-NADP. ALDH-positive foci are found both in normal regions of tumor-bearing livers and prior to the appearance of gross neoplasms. Neoplastic nodules and carcinomas possess a wide variety of ALDH staining patterns between and within lesions. Neoplasms with elevated ALDH activity with propionaldehyde-NAD and/or benzaldehyde-NADP, as well as with no detectable ALDH, have been observed. Changes in ALDH can be identified histochemically at a time in hepatocarcinogenesis when other analytical methods cannot detect significant changes. Moreover, considerable heterogeneity in expression of tumor ALDH is demonstrable by histochemistry.
38 citations
TL;DR: It would appear that carbimide must undergo metabolic conversion in vivo to inhibit hepatic ALDH enzymes, which is supported by the observation of no measurablecarbimide in the liver when ALDH was maximally inhibited following oral CC administration.
Abstract: Oral administration of 7.0 mg/kg calcium carbimide (calcium cyanamide, CC) to the rat produced differential inhibition of hepatic aldehyde dehydrogenase (ALDH) isozymes, as indicated by the time-co...
37 citations
TL;DR: There was a reduction in overall ALDH activity and particularly in the mitochondrial isoenzyme in those with cirrhosis, and by limiting acetaldehyde oxidation it could be responsible for the rapid deterioration in liver function in patients who continue drinking excessively.
Abstract: A method has been developed for simultaneous analysis of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isoenzymes in small (2.5 mg) liver biopsy cores by starch gel electrophoresis. All the currently recognized hepatic isoenzymes coded by ADH1, ADH2, ADH3 and ADH4 can be detected as can the five ALDH isoenzymes. Using this technique we have investigated the isoenzyme composition of liver samples from English and Chinese subjects and a group of chronic alcoholics. Pronounced racial differences in frequency of ADH2 and ALDH phenotypes were found--only 2 (4%) of English controls had the "atypical" ADH2 variant whereas this was present in 42 (84%) of Chinese subjects, and whereas all the English subjects had the rapidly migrating mitochondrial isoenzyme of ALDH, this was absent in 27 (54%) of Chinese. No differences in ADH or ALDH phenotype were seen in the chronic alcoholics, all of whom were of English origin, compared with the English controls, but there was a reduction in overall ALDH activity and particularly in the mitochondrial isoenzyme in those with cirrhosis. The reduction in ALDH activity is probably acquired; by limiting acetaldehyde oxidation it could be responsible for the rapid deterioration in liver function in patients who continue drinking excessively.
34 citations
TL;DR: The acetaldehyde metabolizing capacity in blood of alcoholics and nonalcoholics was investigated by an improved head-space gas chromatographic method and great individual and interindividual variability was observed.
Abstract: The acetaldehyde metabolizing capacity in blood of alcoholics and nonalcoholics was investigated by an improved head-space gas chromatographic method. Great individual and interindividual variability was observed. The mean acetaldehyde oxidizing capacity of 3.51 nmoles/min/ml erythrocyte suspension in alcoholics was significantly lower than the mean of 5.20 nmoles/min/ml in nonalcoholics. Furthermore, treatment of alcoholics with aldehyde dehydrogenase inhibitors reduced the acetaldehyde oxidizing capacity significantly (mean of 1.67 nmoles/min/ml). No acetaldehyde could be detected in blood of nonalcoholics who ingested 0.25 g ethanol/kg body weight whereas levels of 2–14 μM were detected in blood of alcoholics. After disulfiram, an elevation to 7–103 μM in blood of alcoholics was observed.
TL;DR: It was concluded that there was no significant difference in aldehyde-metabolizing capability between male and female HS mice, compared on a per gram of liver basis.
TL;DR: The liver cytosol may be the major site of acetaldehyde oxidation in vivo in man, and the cytosolic enzyme activity was more sensitive to inhibition by disulfiram in vitro.
Abstract: The subcellular distribution of aldehyde dehydrogenase activity was determined in human liver biopsies by analytical sucrose density-gradient centrifugation. There was bimodal distribution of activity corresponding to mitochondrial and cytosolic localizations. At pH 9.6 cytosolic aldehyde dehydrogenase had a lower apparent Kappm for NAD (0.03 mmol l-1), than the mitochondrial enzyme (Kappm NAD = 1.1 mmol l-1). Also, the pH optimum for cytosolic aldehyde dehydrogenase activity (pH 7.5) was lower than that for the mitochondrial enzyme activity (pH 9.0), and the cytosolic enzyme activity was more sensitive to inhibition by disulfiram in vitro. Disulfiram (40 mumol l-1) caused a 70% reduction in cytosolic aldehyde dehydrogenase activity, but only a 30% reduction in mitochondrial enzyme activity after 10 min incubation. The liver cytosol may therefore be the major site of acetaldehyde oxidation in vivo in man.
TL;DR: The inhibition of aldehyde dehydrogenase (AIDH) by cyanamide is dependent on the conversion of the latter to an active metabolite and its lack of inhibitory activity in vitro with purified AIDH enzymes accounts for the in vivo activity of cyanamide in raising ethanol-derived blood acetaldehyde levels to the mM range in the rat.
Abstract: The inhibition of aldehyde dehydrogenase (AlDH) by cyanamide is dependent on the conversion of the latter to an active metabolite. This accounts for the in vivo activity of cyanamide in raising ethanol-derived blood acetaldehyde levels to the mM range in the rat (ED 50 for cyanamide=0.11 mmole/kg) and its lasc of inhibitory activity in vitro with purified AlDH enzymes. Liver mitochondria were shown to catalyze this activation. The Low K m mitochondrial AIDH isozyme was strongly inhibited by cyanamide when measured in intact rat liver mitochondria (I 50 =2.0 μ M). Cyanamide also inhibited yeast AlDH when incubated in the presence, but not in the absence, of rat liver mitochondria (I 50 =7.8 μ M). Using yeast AIDH activity as a measure of cyanamide activation, the subcellular distribution of the cyanamide-activating system was assessed. Microsomes plus an NADPH generating system were equally active as mitochondria in activating cyanamide. In the absence of NADPH, microsomal activity was about half that of mitochondria. Little or no activity was found in the cytosolic fraction. A series of cyanamide analogs and derivatives were screened for their ability to inhibit the low K m AlDH isozyme measured in intact mitochondria. Only monoalkylcyanamides exemplified by n -butylcyanamide showed significatn inhibition. Other cyanamide analogs and derivatives including N-acetylcyanamide, the major urinary metabolite of cyanamide, were inactive in this system.
TL;DR: The results suggest that different isozymes of ALDH are involved in the assay with these two substrates, and the inhibition found in vitro and in vivo was more pronounced when the assays were performed with indole-3-acetaldehyde than with acetaldehyde.
Abstract: The characteristics of human blood aldehyde dehydrogenase with indole-3-acetaldehyde as the substrate were investigated. Blood volumes of less than 25 microliter could be assayed. The Km-value was below 10 microM for indole-3-acetaldehyde and 100 microM for NAD+. The ALDH-activity appeared to be located exclusively in the intracellular fraction of the erythrocytes. Acetaldehyde or ethanol at concentrations up to 1 and 40 mM respectively did not affect the activity. Disulfiram caused a pronounced inhibition of the enzyme both in vitro and in vivo. The blood ALDH-activity in disulfiram-treated patients was not fully restored until 6 weeks after discontinuation of the treatment. The inhibition observed in vitro was reversed completely by 2-mercaptoethanol but only partially by glutathione. No restoration of activity in blood from disulfiram-treated patients was obtained with these two reagents. The inhibition found in vitro and in vivo was more pronounced when the assays were performed with indole-3-acetaldehyde than with acetaldehyde. The results suggest that different isozymes of ALDH are involved in the assay with these two substrates.
TL;DR: The recidivistic patient who discontinues disulfiram and waits several days (to regenerate liver ALDH activity) before drinking will be exposed to even higher ethanol‐derived blood acetaldehyde levels than usual, which may induce further alcohol‐associated organ damage and alcohol dependence.
Abstract: During disulfiram therapy erythrocyte aldehyde dehydrogenase (ALDH) was fully inhibited. The time for total loss of erythrocyte ALDH activity ranged from 36 to 120 hr. In contrast to the 85% recovery of in vitro disulfiram-inhibited ALDH activity, this in vivo disulfiram-ALDH inhibition could not be reversed by mercaptoethanol. It is proposed that the in vivo and in vitro mechanisms of ALDH inhibition by disulfiram differ. Erythrocyte ALDH activity can be readily monitored to determine patient compliance and is an accessible model for investigations of in vivo mechanisms of drug inhibition. Because the disulfiram-inhibited erythrocyte ALDH is not regenerated until new erythrocytes are made (120 days), a significant portion of the extrahepatic acetaldehyde metabolic capacity remains inhibited for long periods after disulfiram is discontinued. Thus, the recidivistic patient who discontinues disulfiram and waits several days (to regenerate liver ALDH activity) before drinking will be exposed to even higher ethanol-derived blood acetaldehyde levels than usual, which may induce further alcohol-associated organ damage and alcohol dependence.
TL;DR: Aldehyde dehydrogenase subcellular distribution and activity were studied in the Yoshida hepatoma AH-130 and rat liver and the return of activity was slower for the hepatoma and neonatal liver than for the adult liver enzyme.
TL;DR: In the unusual ALDH group, facial flushing, increase of pulse rate and decrease in diastolic blood pressure associated with accumulation of blood acetaldehyde were shown, and the alteration of catecholamine metabolism, decrease in urinary VMA and increase in urinary MHPG was recognized in both groups.
TL;DR: It is proposed that binding of NAD+ limits access of disulfiram to the thiols at the active site but provides a situation that favours an electrophilic attack of cyanamide and ACP on theThiol groups.
Journal Article•
TL;DR: Induction of the tumor-specific ALDH phenotype is extended to another family of carcinogens, the nitrosamines, and it is confirmed that the phenotypic change is due to an initiator-induced, stable genetic change that is expressed relatively late in hepatocarcinogenesis.
Abstract: Hepatomas induced in postweanling male Sprague-Dawley rats by sequential dietary 2-acetylaminofluorene (AAF):phenobarbital (PB) exposure possess an aldehyde dehydrogenase (ALDH) phenotype qualitatively and quantitatively different from that of normal liver. To assess the generality of this phenotype, we have evaluated the ability of another family of carcinogens and an additional tumor induction protocol to induce this change. One-day-old female Sprague-Dawley rats were given injections i.p. of either diethylnitrosamine (DEN) or AAF (0.15 µmol/g body weight in corn oil). Animals were weaned onto a 30% protein diet containing 0.05% PB. At intervals up to 27 weeks after weaning, animals were sacrificed, and the ALDH phenotype of both normal liver and any lesions was characterized. Elevated NAD(P)-dependent, benzaldehyde-oxidizing activity, the major marker of the tumor-specific ALDH phenotype, was not detected in any normal liver during the experiment. Only DEN:PB-treated animals developed hepatic tumors. Twenty-one tumors were found in 14 animals, the first being observed at 105 days of age. Sixteen of the tumors possessed the tumor-specific ALDH phenotype as determined by changes in total ALDH activity, isozyme patterns, and/or immunochemical methods.
Another significant change in hepatic ALDH, characterized by elevated NAD-dependent activity, was observed in normal liver of some animals receiving PB following either DEN (seven of 34) or AAF (11 of 34). Only one animal in each of the control groups (one of 17 PB controls; one of 16 basal-diet controls) had marginally elevated NAD-dependent ALDH activity. This ALDH activity is distinguishable from the normal liver ALDHs and from the tumor-specific phenotype by a number of properties, but it appears identical to a promotion-associated hepatic ALDH observed previously in some animals initiated with dietary AAF followed by dietary PB promotion.
These results extend induction of the tumor-specific ALDH phenotype to another family of carcinogens, the nitrosamines, and confirm that the phenotypic change is due to an initiator-induced, stable genetic change that is expressed relatively late in hepatocarcinogenesis. The appearance of an additional, independent change in ALDH activity during the promotion phase of hepatocarcinogenesis suggests that changes in ALDH activity may also be useful in understanding the interactions of initiators and promoters during tumorigenesis.
TL;DR: L'hydrolyse du PNPA ne se produit pas au niveau du site actif de the reaction deshydrogenase de la reaction desHydrogenase.
Abstract: L'hydrolyse du PNPA ne se produit pas au niveau du site actif de la reaction deshydrogenase
TL;DR: It was concluded that, in the reconstituted systems, acetaldehyde played a dominant role in controlling the rate of ethanol oxidation and the possible importance of acetaldehyde in governing ethanol oxidation in vivo is discussed.
TL;DR: These studies show that a select ALDH isozyme is sensitive to inhibition during membrane lipid peroxidation whereas other isozymes may be involved in the metabolism of aldehydic per oxidation products.
Abstract: Recent findings have shown that microsomal membrane lipid peroxidation generates a variety of reactive aldehydic products. The interaction of lipid peroxidation products with hepatic aldehyde dehydrogenases (ALDH) was studied using rat liver subcellular fractions. The well-documented membrane peroxidation product malondialdehyde (MDA) was studied to determine if ALDH isozymes play a role in metabolism of this aldehyde. The cytosolic and mitochondrial hepatic subcellular fractions were found to contain ALDH isozymes capable of oxidizing MDA. The kinetic properties of a cytosolic ALDH (Km of approximately 16 μM) suggest that this enzyme may be involved in the metabolism of MDA in vivo. Both the cytosolic and mitochondrial fractions also contained an ALDH isozyme with Km values in the millimolar range. Addition of the cytosolic fraction of rat liver produced a significant decrease in the accumulation of MDA during CCl4-induced microsomal membrane lipid peroxidation but did not protect cytochrome P-450 from destruction. The mitochandrial low Km ALDH isozyme was found to be a target enzyme for inhibition during in vitro microsomal lipid peroxidation. These studies show that a select ALDH isozyme is sensitive to inhibition during membrane lipid peroxidation whereas other isozymes may be involved in the metabolism of aldehydic peroxidation products.
TL;DR: The general characteristics of the NAD-dependent aldehyde dehydrogenase present in blood were examined to find suitable assay conditions for activity measurements with whole blood samples from disulfiram-treated patients, and implantation of 1 g of disulforam in patients pretreated for 10 days with oral disulfIRam did not cause a delayed return of ALDH activity.
Abstract: The general characteristics of the NAD-dependent aldehyde dehydrogenase (ALDH) present in blood were examined to find suitable assay conditions for activity measurements with whole blood samples from disulfiram-treated patients. The ALDH activity was measured as the rate of acetaldehyde disappearance. The ALDH activity in blood from alcoholics before disulfiram treatment was 39% lower than that found in blood from control subjects. Disulfiram caused a decreased ALDH activity in vitro. Similarly, a decreased activity was found in blood from patients treated with disulfiram orally (400 mg/day). The activity declined to a level being 60% of the control activity during the first week of treatment. A significant inhibition was observed 1 week after the treatment was discontinued. Implantation of 1 g of disulfiram in patients pretreated for 10 days with oral disulfiram did not cause a delayed return of ALDH activity, suggesting that the amounts of disulfiram released were too low to affect the ALDH activity in blood.
TL;DR: Steady-state kinetic analyses show that the Bovine lens cytoplasmic aldehyde dehydrogenase exhibits a compulsory-ordered ternary-complex mechanism with NAD+ binding before acetaldehyde.
Abstract: Bovine lens cytoplasmic aldehyde dehydrogenase exhibits Michaelis-Menten kinetics with acetaldehyde, glyceraldehyde 3-phosphate, p-nitrobenzaldehyde, propionaldehyde, glycolaldehyde, glyceraldehyde, phenylacetylaldehyde and succinic semialdehyde as substrates. The enzyme was also active with malondialdehyde, and exhibited an esterase activity. Steady-state kinetic analyses show that the enzyme exhibits a compulsory-ordered ternary-complex mechanism with NAD+ binding before acetaldehyde. The enzyme was inhibited by disulfiram and by p-chloromercuribenzoate, and studies with with mercaptans indicated the involvement of thiol groups in catalysis.
TL;DR: Radical scavenging by the addition of the flavonoid, cyanidanol, or by pretreatment with vitamin E abolished ethane release, in agreement with lipid peroxidation as a source of alkane production during aldehyde metabolism.
Abstract: Infusion of aldehyde such as acetaldehyde, propionaldehyde or benzaldehyde to perfused rat liver leads to an increase in hepatic ethane production. Half-maximal effect was obtained with about 20 microM acetaldehyde, a concentration range found in plasma during ethanol metabolism. Compounds which metabolically generate aldehydes such as monoamines (benzylamine, phenylethylamine) as substrates for monoamine oxidase or ethanol as substrate for alcohol dehydrogenase [A. Muller and H. Sies (1982) Biochem. J. 206, 153-156] are also able to elicit ethane release. Results obtained with inhibitors of hepatic aldehyde metabolism (pargyline or cyanamide) or of monamine oxidase (pargyline or tranylcypromine) suggest that metabolism of the aldehydes is required for ethane production. Radical scavenging by the addition of the flavonoid, cyanidanol, or by pretreatment with vitamin E (alpha-tocopherol) abolished ethane release, in agreement with lipid peroxidation as a source of alkane production during aldehyde metabolism.
TL;DR: The present experiments demonstrated that the rise in blood acetaldehyde levels coincided with the inhibition rates of the low-Km ALDH activity by the cephem antibiotics, which were in the order: LMOX greater than CMD greater than CPZ greater than CMZ.
TL;DR: The results provide a consistent explanation for the acetaldehyde-mediated extreme sensitivity to moderate alcohol ingestion shown normally by about 50% of oriental subjects and during disulfiram (Antabuse) therapy by all subjects.
TL;DR: Individuals suffering from the aversive symptoms of that syndrome will be protected from excessive drinking and the related problems, and sites exhibiting high alcohol dehydration activity may specifically be affected in alcoholics.
Abstract: Evidence is growing that acetaldehyde is responsible for some toxic effects after ethanol intake. Large individual and racial differences in blood and breath acetaldehyde concentrations are observed after alcohol consumption. In many Orientals but few Caucasians extremely high blood acetaldehyde levels occur leading to an acute aldehyde syndrome also observed after treatment with aldehyde dehydrogenase inhibitors. Individuals suffering from the aversive symptoms of that syndrome will be protected from excessive drinking and the related problems. In chronic aldehydism slightly elevated aldehyde concentrations are observed possibly leading to organic injury due to the cytotoxic action of acetaldehyde. Sites exhibiting high alcohol dehydrogenase activity may specifically be affected in alcoholics.