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PubMed2006

Alcohol dehydrogenase 2 His47Arg polymorphism influences drinking habit independently of aldehyde dehydrogenase 2 Glu487Lys polymorphism: analysis of 2,299 Japanese subjects.

Although the functional effect of alcohol dehydrogenase 2 (ADH2) His(47)Arg polymorphism has been elucidated, its effect on habitual drinking remains unknown. Here, we conducted a cross-sectional study in 2,299 nonalcoholic Japanese subjects (989 men and 1,310 women). Drinking status, ethanol consumption, and physical reaction to one glass of beer were examined with regard to ADH2 and aldehyde dehydrogenase 2 (ALDH2) polymorphism. Strength of associations were assessed by age-, sex-, smoking status-, and genotype-adjusted odds ratios and their 95% confidence intervals. ADH2 His/Arg and Arg/Arg genotypes showed higher risk for habitual drinking. Among men, ALDH2 genotype- and confounder-adjusted odds ratios (95% confidence intervals) were 1.30 (0.89-1.89) and 3.16 (1.03-9.70), and this trend was significant (P = 0.024). A similar trend was observed among women. The combination genotypes of two polymorphisms revealed the clear effect of the ADH2 Arg allele among those with ALDH2 Glu/Lys in both sexes (P(trend) = 0.007 for men and 0.024 for women). Physical reactions, such as flushing and palpitation, were significantly less common in those with Arg/Arg compared with other ADH2 genotypes, and this was marked when combined with ALDH2 Glu/Lys. Heavy drinker status was also strongly associated with ADH2 Arg alleles. In conclusion, this study showed the strong effect of ADH2 His(47)Arg polymorphism on habitual drinking regardless of ALDH2 genotype.

Adult↗
PubMed2002

Aldehyde dehydrogenase 2 gene is a risk factor for myocardial infarction in Japanese men.

In epidemiological studies, moderate alcohol consumption has been consistently associated with a reduced risk of myocardial infarction (MI). About half of Japanese show an extremely high sensitivity to alcohol (ethanol), which is due to a missense mutation from glutamic acid (Glu) to lysine (Lys) at codon 487 in an isoenzyme of aldehyde dehydrogenase (ALDH2) with a low Km. We obtained a preliminary result that subjects homozygous for the Lys 487 allele had higher risk for myocardial infarction. The purpose of the present study was to assess this hypothesis by employing a larger cohort of subjects with MI. The experimental group consisted of 342 male subjects with demonstrated MI who were selected randomly from our outpatient clinic. As controls, we employed 1,820 male subjects with no cardiovascular complications who were selected from the Suita Study. All subjects provided their written informed consent to participate in the genetic analyses. Subjects with MI were older and had higher body mass index, higher prevalence of diabetes mellitus, higher prevalence of smoking habit, higher prevalence of the Lys/Lys genotype (homozygous for Lys 487 allele), and lower high density lipoprotein (HDL) cholesterol level (HDL-C). The ALDH2 genotype affected the level of alcohol consumption, and HDL-C. Multiple logistic analyses indicated that the odds ratio of the Lys/Lys genotype to the Lys/Glu+Glu/Glu genotype was 1.56 (p=0.0359). Inclusion of HDL-C as one of the independent variables downplayed the importance of the ALDH2 genotype. This may indicate that the ALDH2 genotype affects MI via its effects on HDL-C. In conclusion, the ALDH2 Lys/Lys genotype is a risk factor for myocardial infarction in Japanese men due to its influence on HDL cholesterol level.

Alcohol Drinking↗
PubMed2002

Epidemiologic study of the association of low-Km mitochondrial acetaldehyde dehydrogenase genotypes with blood pressure level and the prevalence of hypertension in a general population.

In Japanese and other Asians, the prevalence of genetically decreased mitochondrial aldehyde dehydrogenase (ALDH2) activity is higher than in Caucasians. The aim of this study was to elucidate the relation between ALDH2 genotypes and blood pressure levels or hypertension in Japanese. After obtaining informed consent for genetic analysis from 917 men and 1,478 women who lived in a mountainous farming region near Kyoto and who were free from cardiovascular disease and liver dysfunction, the authors identified the ALDH2 genotype in all subjects. Differences in blood pressure level among genotypes were then compared by analysis of covariance, and the relation between genotypes and hypertension was also analyzed by logistic regression analysis. The frequencies of genotypes *1/*1, *1/*2, and *2/*2 were 44.7%, 46.9% and 8.4% in men, and 50.1%, 43.2% and 6.8% in women, respectively. In men, systolic and diastolic blood pressures tended to decrease in the order of *1/*1>*1/*2>*2/*2. However, adjustment for confounding factors including alcohol consumption resulted in the disappearance of significance. Logistic regression analysis adjusted for the same confounding factors for men showed that the odds ratios (OR) of being hypertensive in the *2 allele to not having *2 allele were 0.67 (95% confidence interval (CI): 0.47-0.96). However, in the subgroup analyses, this relation was not observed in the group having a below-median level of alcohol consumption (OR = 0.92; 95% CI: 0.53-1.62) or in the group not taking antihypertensive agents (OR = 0.77; 95% CI: 0.52-1.15). Furthermore, we did not observe any relation between the ALDH2/*2 allele and hypertension in women (OR = 1.07; 95% CI: 0.80-1.42). The results suggest that there may be no causal relation between hypertension and the ALDH2 genotype per se, after excluding for some confounding factors, especially for alcohol drinking.

Adult↗
PubMed2003

Religious influences on heavy episodic drinking in Chinese-American and Korean-American college students.

OBJECTIVE: The purpose of the current study was to examine religious influences that relate to heavy episodic drinking in Chinese-American and Korean-American college students, after controlling for the effects of ALDH2 gene status. METHOD: Participants (159 Chinese-American and 188 Korean-American college students) were assessed for the presence or absence of a heavy drinking episode in the past 2 weeks, using a gender-specific measure. All participants also reported their religious affiliation and the number of religious services attended in the past year, and were genotyped at the ALDH2 locus. RESULTS: Chinese were less likely than Koreans to be affiliated with any religion (55% vs 84%), but were more likely to be affiliated with Eastern religions (12% vs 1%). When controlling for the effects of ALDH2 status, service attendance significantly related to lower rates of heavy episodic drinking in Koreans, but did not reach significance in Chinese. The relationship was significant, however, in Chinese affiliated with Western religions. In addition, religious service attendance only related to heavy drinking in individuals with ALDH2*1/*1 genotype. CONCLUSIONS: These results suggest religious service attendance is inversely related to heavy episodic drinking in Korean Americans and in Chinese Americans with Western religious affiliation. Moreover, service attendance appears to more strongly influence heavy drinking in individuals who are not already protected by an ALDH2*2 allele.

Adult↗
PubMed2005

Kimchi and soybean pastes are risk factors of gastric cancer.

AIM: This case-control study investigated the effects of kimchi, soybean paste, fresh vegetables, nonfermented alliums, nonfermented seafood, nonfermented soybean foods, and the genetic polymorphisms of some metabolic enzymes on the risk of gastric cancer in Koreans. METHODS: We studied 421 gastric cancer patients and 632 age- and sex-matched controls. Subjects completed a structured questionnaire regarding their food intake pattern. Polymorphisms of cytochrome P450 1A1 (CYP1A1), cytochrome P450 2E1 (CYP2E1), glutathione S-transferase mu 1 (GSTM1), glutathione S-transferase theta 1 (GSTT1) and aldehyde dehydrogenase 2 (ALDH2) were investigated. RESULTS: A decreased risk of gastric cancer was noted among people with high consumption of nonfermented alliums and nonfermented seafood. On the other hand, consumption of kimchi, and soybean pastes was associated with increased risk of gastric cancer. Individuals with the CYP1A1 Ile/Val or Val/Val genotype showed a significantly increased risk for gastric cancer. Increased intake of kimchi or soybean pastes was a significant risk factor for the CYP1A1 Ile/Ile, the CYP2E1 c1/c1, the GSTM1 non-null, the GSTT1 non-null, or the ALDH2 *1/*1 genotype. In addition, eating soybean pastes was associated with the increased risk of gastric cancer in individuals with the GSTM1 null type. Nonfermented alliums were significant in individuals with the CYP1A1 Ile/Ile, the CYP2E1 c1/c2 or c2/c2, the GSTT1 null, the GSTT1 non-null, or the ALDH2 *1/*2 or *2/*2 genotype, nonfermented seafood was those with the CYP1A1 Ile/Ile, the CYP2E1 c1/c1, the ALDH2 *1/*1 genotype or any type of GSTM1 or GSTT1. In homogeneity tests, the odds ratios of eating kimchi for gastric cancer according to the GSTM1 or GSTT1 genotype were not homogeneous. CONCLUSION: Kimchi, soybean pastes, and the CYP1A1 Ile/Val or Val/Val are risk factors, and nonfermented seafood and alliums are protective factors against gastric cancer in Koreans. Salt or some chemicals contained in kimchi and soybean pastes, which are increased by fermentation, would play important roles in the carcinogenesis of stomach cancer. Polymorphisms of the CYP1A1, CYP2E1, GSTM1, GSTT1, and ALDH2 genes could modify the effects of some environmental factors on the risk of gastric cancer.

Adult↗
PubMed2002

Genotype of ethanol metabolizing enzyme genes by oligonucleotide microarray in alcoholic liver disease in Chinese people.

OBJECTIVE: To explore the relationship between genetic polymorphisms of the ethanol metabolizing enzymes and the occurrence of alcoholic liver disease (ALD). METHODS: Sixty-five healthy male controls and 165 alcoholisms (including 122 ALD patients and 43 male alcohol abusers without liver complications defined as alcohol-dependent) were analyzed by polymerase chain reaction and hybridized with oligonucleotide microarray to detect the polymorphisms of the ethanol metabolizing enzymes genes. RESULTS: The frequencies of alcohol dehydrogenase gene 2 * 1 ( ADH2 * 1 ) allele were shown as 37.69%, 46.51% and 59.02% in control, alcohol-dependent and ALD groups respectively; while those of ADH2 * 2 allele were shown as 62.31 %, 53.49% and 40.98% respectively. No ADH2 * 3 was detected in any of the subjects. The frequency of ADH2 * 1 was significantly higher in alcoholisms (ALD group and alcohol-dependent group) than in healthy controls ( P < 0. 01), and significantly higher in ALD group than in alcohol-dependent group ( P < 0.05) . The frequency of ADH3 * 2 was significantly higher in alcohol-dependents than in healthy controls ( P < 0.05) . The frequencies of ALDH2 * 2 allele mutation were significantly lower in alcoholisms than that in the healthy controls, and the deference between ALD group and alcohol-dependent group was significant. No homozygotes for the mutant ALDH2 * 2 allele were found in either alcoholic groups. CONCLUSIONS: Polymorphic ADH2, ADH3 and ALDH2 genes can affect the propensity for alcohol drinking in Chinese. The alleles of ADH2 * 2, ADH3 * 1 and ALDH2 * 2 are most likely to play a protective role against excessive consumption. ADH2 * 2 and ALDH2 X 2 may contribute to susceptibility for ALD.

Alcohol Dehydrogenase↗
PubMed2003

[Relationship between ALDH gene polymorphism and alcoholic liver diseases].

OBJECTIVE: To study the relationship between aldehyde dehydrogenase (ALDH) gene polymorphism and alcoholic liver disease, and investigate the genetic pathogenesis of alcoholic liver disease (ALD). METHODS: PCR, restriction endonuclease and electrophoresis were used, to detect the genotypes and alleles frequencies of ALDH gene in patients in the control group, alcohol dependent group and ALD group, and each group contained 20 patients. RESULTS: The frequencies of ALDH2*1 and ALDH2*2 allele had statistic significance between control group and ALD group (x2=4.80, P<0.05), and no statistic significance between control group and alcohol dependent group. ALDH2*1/*1 was predominant in alcohol dependent group and ALD group, while ALDH2*2/*2 was not detected. CONCLUSIONS: The gene polymorphism of ALDH is close to ALD. The allele of ALDH2*2 may be a negative risk factor for the developing of ALD

Adult↗
PubMed1991

Stomach and duodenal alcohol and aldehyde dehydrogenase isozymes in Chinese.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isozyme phenotypes were determined in surgical and endoscopic biopsies of the stomach and duodenum by agarose isoelectric focusing. gamma-ADH was found to be the predominant form in the mucosal layer whereas beta-ADH was predominant in the muscular layer. Low-Km ALDH1 and ALDH2 were found in the stomach and duodenum. High-Km ALDH3 isozymes occurred only in the stomach but not in the duodenum. The isozyme patterns of gastric mucosal ALDH2 and ALDH3 remained unchanged in the fundus, corpus, and antrum. The stomach ALDH3 isozymes exhibited a Km value for acetaldehyde of 75 mM, and an optimum for acetaldehyde oxidation at pH 8.5. Since the Km value was high, ALDH3 contributed very little, if any, to gastric ethanol metabolism. The activities of ALDH in the gastric mucosa deficient in ALDH2 were 60-70% of that of the ALDH2-active phenotypes. These results indicate that Chinese lacking ALDH2 activity may have a lower acetaldehyde oxidation rate in the stomach during alcohol consumption.

Adult↗
PubMed1983

Differences in the isozymes involved in alcohol metabolism between caucasians and orientals.

Acute alcohol intoxication is far more commonly observed in Orientals than Caucasians. The human liver contains several cytosolic and microsomal ADHs. One of the major cytosolic ADH isozymes controlled by a gene at the ADH2 locus differs between Caucasians and Orientals. Most Caucasians have the usual enzyme consisting of usual beta 1 subunit, while nearly 90% of Orientals have the atypical enzyme consisting of the atypical beta 2 subunit. The specific activity of the atypical enzyme is several times higher at pH 10 and nearly 100 times higher at physiologic pH than the usual enzyme. Km values for ethanol, NAD, acetaldehyde, and NADH are several times higher for the atypical enzyme than for the usual enzyme. The usual enzyme is rapidly inactivated by iodoacetate, indicating the existence of an "active-site cysteine" in the molecule. In contrast, the atypical enzyme is resistant to iodoacetate inactivation. Peptide mapping analysis revealed that the active site Cys in the usual beta 1 subunit is replaced by His in the atypical beta 2 subunit. A remarkable structural homology exists at the active site of horse and human enzymes. In the usual beta 1 beta 1 enzyme, as in the horse enzyme, the catalytic Zn is expected to link to the sensitive Cys at position 47, His at position 67, and Cys (presumably) at position 174, thus forming the active site. In contrast, the active site of the atypical beta 2 beta 2 enzyme is expected to consist of the catalytic Zn linked to His at position 47, His at position 67, and Cys (presumably) at position 174. The resistance of the atypical beta 2 beta 2 to inactivation by iodoacetate is a direct consequence of the replacement of the sensitive Cys at position 47 by His. Liver ALDH components also differ between Caucasians and Orientals. Virtually all Caucasians have two major ALDH isozymes, ALDH1 and ALDH2, while approximately 50% of Orientals have only the ALDH1 isozyme (cytosolic) missing ALDH2 isozyme (presumably mitochondrial). ALDH1 consists of four subunits with a molecular weight of 56,500, and ALDH2 consists of four subunits with a molecular weight of 52,600. The two isozymes do not share any common subunit. Examination of liver extracts by two-dimensional crossed immunoelectrophoresis revealed that an atypical Oriental liver with no ALDH2 isozyme contained an enzymatically inactive but immunologically cross-reactive material corresponding to ALDH2, besides the active ALDH1 isozyme.(ABSTRACT TRUNCATED AT 400 WORDS)

Alcohol Dehydrogenase↗
PubMed1994

[Relationship between alcoholism and genotypes of acetaldehyde-metabolizing enzymes].

The genotypes of the CYP2E1 and ALDH2 loci in alcoholic and non-alcoholic (healthy) Japanese were investigated to examine the relationship between the polymorphisms of CYP2E1 (C1/C2) and ALDH2 (ALDH2*1/ALDH2*2), and the susceptibility to alcoholism. There was no significant difference in C2 gene frequency between alcoholics (0.20) and non-alcoholics (0.19), while there was a significant difference in ALDH2 allele frequency, suggesting that the C2 allele of CYP2E1 may have nothing to the risk of developing alcoholism in Japanese, whereas the ALDH2*1 allele may influence drinking behavior and the development of alcoholism.

Alcoholism↗
PubMed1998

Clinical characteristics and disease course of alcoholics with inactive aldehyde dehydrogenase-2.

Inactive aldehyde dehydrogenase-2 (ALDH2) is known as a genetic negative risk factor for the development of alcoholism. In alcoholics with inactive ALDH2, unidentified factors that overcome the adverse reactions of high blood acetaldehyde concentration after drinking may increase such persons' susceptibility to alcoholism. Comparison of clinical characteristics, including sociofamilial backgrounds and psychopathologies, failed to show significant differences between alcoholics with inactive ALDH2 (inactive group) and those with active ALDH2 (active group). Examination of the temporal profile of disease development showed that the inactive group experienced each stage or event in the history of drinking and alcoholism 1 to 5 years later in life than the active group; however, not all comparisons reached statistically significant levels. Although preliminary, these results suggest that an inactive ALDH2-mediated delay in the occurrence of alcohol-related problems seems to contribute to the suppression of alcoholism development.

Acetaldehyde↗
PubMed2006

Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease?

Case-control studies that have investigated the association between alcoholism and alcohol-induced liver damage and the ADH2, ADH3, CYP2E1, and ADLH2 polymorphisms have reported controversial or inconclusive results. Thus, we conducted a meta-analysis of 50 association studies of the above polymorphisms. We explored potential sources of heterogeneity and bias, performed subgroup analyses by racial background and sex, performed sensitivity analyses for studies not in Hardy-Weinberg equilibrium, and performed a subgroup analysis for cases that met strict criteria for alcoholism. The present meta-analysis underscores significant associations of ADH2*1, ADH3*2, and ALDH2*1 alleles and the risk of alcoholism (OR = 1.89 [95% CI 1.56-2.28], 1.32 [95% CI 1.12-1.57], and 4.35 [95% CI 3.04-6.23], respectively). The subsequent subgroup analyses showed association for ADH2*1 and ADH3*2 only in East Asians (OR = 2.23 [95% CI 1.81-2.74] and 1.91 [95% CI 1.45-2.53], respectively) and East Asian males (OR = 2.21 [95% CI 1.57-3.10], 1.69 [95% CI 1.10-2.59], respectively). In East Asian males, the OR for ALDH2*1 was 3.66 (95% CI 1.68-7.96). In Caucasians, sensitivity analysis revealed an association for ADH2*1 in alcoholism (OR = 1.62 [95% CI 1.22-1.89]). When strict criteria were imposed, the pattern of results remained unaltered. For liver disease, there were no significant associations for ADH2*1, ADH3*2, or ALDH2*1 in all subpopulations. The CYP2E1 polymorphism showed no association whatsoever. There is evidence that alleles are mainly dominant. In conclusion, there was heterogeneity between studies in alcoholism for ADH2, ADH3, and ALDH2, and lack of bias in all polymorphisms. The above findings reinforce the need for more rigorous studies, and for regular synthesis of studies' results.

Alcohol Dehydrogenase↗
PubMed1995

Dopamine transporter gene polymorphism and alcoholism.

In this search for a possible association between the dopamine transporter gene (DAT1) polymorphism and alcoholism, 655 Japanese alcoholics were grouped according to their aldehyde dehydrogenase-2 (ALDH2) genotypes. Because inactive ALDH2 is an established negative risk factor for alcoholism, alcoholics with the mutant allele, ALDH2*2, were considered a relatively homogeneous group. The frequency of the 7-repeat allele of the DAT1 variable number of tandem repeat was significantly higher in alcoholics with ALDH2*2 than in control subjects. These results are consistent with the hypothesis that alteration in the dopaminergic system plays some role in the development of alcoholism.

Alcoholism↗
PubMed1994

Characterization of the three genotypes of low Km aldehyde dehydrogenase in a Japanese population.

A deficiency in low Km aldehyde dehydrogenase (ALDH2) is regarded as the main factor responsible for "Oriental flushing" and other symptoms due to alcohol sensitivity. In this study, the relationship of the ALDH2 genotype to alcohol-associated symptoms and drinking behavior was investigated in 524 Japanese workers, using a new, rapid, and nonisotopic polymerase chain reaction (PCR) method. Differences in the frequency of alcohol-associated manifestations between the normal homozygote and the other deficient types were apparent. In addition, among the ALDH2-deficient individuals, the atypical homozygote was obviously more hypersensitive to alcohol than the heterozygote, judging from the frequency of flushing or other drinking-associated manifestations with a small dose of alcohol. Drinking frequency also apparently decreased in the following order: typical homozygote, heterozygote, atypical homozygote. Similarly, mean amounts of alcohol consumption also decreased in the same order, although considerable variation existed within the typical homozygote and the heterozygote group. In contrast, neither the manifestations nor the drinking behavior were, in general, influenced by polymorphism of the alcohol dehydrogenase beta-subunit (ADH2) gene in males. These findings further indicate the important contribution of the ALDH2 genotype to alcohol sensitivity in Orientals.

Adult↗
PubMed1993

Biological monitoring of toluene and DNA polymorphism in humans.

The effects of genetic polymorphism in aldehyde dehydrogenase 2 (ALDH2) on alcohol intakes and toluene metabolism were studied in workers who handle toluene. The genotypes of ALDH2 were divided into three groups, which were the homozygous genotype of normal ALDH2 (NN), the homozygous genotype of an inactive one (DD) and the heterozygous genotype of normal and inactive ones (ND), using the polymerase chain reaction (PCR) method in a solution containing ddGTP. The alcohol intake of the DD group was very small. On the other hand, the alcohol intake of NN group was higher than that of DD group. That of ND group was about half way between those of NN group and DD group. The alteration of toluene metabolism by the polymorphism of ALDH2 was not clear because the exposure levels of the workers to toluene were low.

Adult↗
PubMed1989

Kinetic evidence for human liver and stomach aldehyde dehydrogenase-3 representing an unique class of isozymes.

Substrate and coenzyme specificities of human liver and stomach aldehyde dehydrogenase (ALDH) isozymes were compared by staining with various aldehydes including propionaldehyde, heptaldehyde, decaldehyde, 2-furaldehyde, succinic semialdehyde, and glutamic gamma-semialdehyde and with NAD+ or NADP+ on agarose isoelectric focusing gels. ALDH3 isozyme was isolated from a liver via carboxymethyl-Sephadex and blue Sepharose chromatographies and its kinetic constants for various substrates and coenzymes were determined. Consistent with the previously proposed genetic model for human ALDH3 isozymes (Yin et al., Biochem. Genet. 26:343, 1988), a single liver form and multiple stomach forms exhibited similar kinetic properties, which were strikingly distinct from those of ALDH1, ALDH2, and ALDH4 (glutamic gamma-semialdehyde dehydrogenase). A set of activity assays using various substrates, coenzymes, and an inhibitor to distinguish ALDH1, ALDH2, ALDH3, and ALDH4 is presented. As previously reported in ALDH1 and ALDH2, a higher catalytic efficiency (Vmax/Km) for oxidation of long-chain aliphatic aldehydes was found in ALDH3, suggesting that these enzymes have a hydrophobic barrel-shape substrate binding pocket. Since the Km value for acetaldehyde for liver ALDH3, 83 mM, is very much higher than those of ALDH1 and ALDH2, ALDH3 thus represents an unique class of human ALDH isozymes and it appears not to be involved in ethanol metabolism.

Aldehyde Dehydrogenase↗
PubMed1992

Genetic polymorphism and activities of human lung alcohol and aldehyde dehydrogenases: implications for ethanol metabolism and cytotoxicity.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) exhibit genetic polymorphism and tissue specificity. ADH and ALDH isozyme phenotypes from 39 surgical Chinese lung specimens were identified by agarose isoelectric focusing. The identity of the lung beta-ADHs was further demonstrated by their characteristic pH-activity profiles for ethanol oxidation, Km values for NAD and ethanol, and inhibition by 4-methylpyrazole or 1,10-phenanthroline. The beta 2 allele, coding for beta 2 polypeptide, was found to be predominant in the lung specimens studied. The ADH activities in the lungs with the homozygous phenotype ADH2 2-2 (exhibiting beta 2 beta 2) and ADH2 1-1 (exhibiting beta 1 beta 1) and the heterozygous phenotype ADH2 2-1 (exhibiting beta 2 beta 2, beta 2 beta 1, and beta 1 beta 1) were determined to be 999 +/- 77, 48 +/- 17, and 494 +/- 61 nmol/min/g tissue, respectively. Fifty-one percent of the specimens studied lacked the ALDH2 activity band on the isoelectric focusing gels. The activities in the lung tissues with the ALDH2-active phenotype and the inactive phenotype were determined to be 30 +/- 3 and 17 +/- 1 nmol/min/g tissue, respectively. These findings indicate that human pulmonary ethanol-metabolizing activities differ significantly with respect to genetic polymorphism at both the ADH2 and the ALDH2 loci. The results suggest that individuals with high Vmax beta 2-ADH and deficient in low-Km mitochondrial ALDH2, accounting for approximately 45% of the Chinese population, may end up with acetaldehyde accumulation during alcohol consumption, rendering them vulnerable to tissue injury caused by this highly reactive and toxic metabolite.

Adult↗
PubMed1994

S-methyl N,N-diethylthiolcarbamate sulfone, an in vitro and in vivo inhibitor of rat liver mitochondrial low Km aldehyde dehydrogenase.

S-Methyl N,N-diethylthiolcarbamate sulfone (DETC-Me sulfone) was investigated for its rat liver mitochondrial low Km aldehyde dehydrogenase (ALDH2) inhibitory properties. DETC-Me sulfone inhibited ALDH2 in vitro (IC50 = 3.8 microM) and in vivo (ID50 = 170 mumol/kg; 31 mg/kg). Maximum inhibition (60%) of ALDH2 was observed 8 hr after DETC-Me sulfone administration. In addition, incubation of S-methyl N,N-diethylthiolcarbamate (DETC-Me) or S-methyl N,N-diethylthiolcarbamate sulfoxide (DETC-Me sulfoxide) with rat liver microsomes and an NADPH-generating system failed to produce DETC-Me sulfone. Furthermore, DETC-Me sulfone could not be detected in plasma from rats treated with either DETC-Me sulfoxide or DETC-Me sulfone. In conclusion, DETC-Me sulfone inhibited ALDH2 in vitro and in vivo. However, there was no evidence suggesting that DETC-Me sulfoxide was metabolized to DETC-Me sulfone.

Aldehyde Dehydrogenase↗