Aldehyde dehydrogenase 2 (ALDH2), as one of the most important alcohol metabolizing enzymes, plays a significant role in the detoxification process of acetaldehyde which is a main carcinogenic product of alcoholic metabolism. Alteration in its genotypes (particularly at the site of rs671) is closely associated with a variety of tumors in drinkers. Recent advance in the research of the association of the ALDH2 gene rs671 polymorphisms with cancer susceptibility in drinkers is reviewed.
Alcohol Drinking ; genetics ; Aldehyde Dehydrogenase ; genetics ; Aldehyde Dehydrogenase, Mitochondrial ; Genetic Predisposition to Disease ; Humans ; Neoplasms ; etiology ; genetics ; Polymorphism, Genetic

OBJECTIVE: To explore alcohol pharmacokinetics as well as acetaldehyde level in peripheral blood in human subjects with different ALDH2 genotypes after drinking. METHODS: Venous blood samples of 14 unrelated volunteers were collected. Polymerase chain reaction-restriction fragment length polymorphism technology was adopted for DNA extraction and ALDH2 genotyping. The volunteers were asked to drink beer at certain doses. The concentration of alcohol and acetaldehyde were assayed by headspace gas chromatography method at different time. The pharmacokinetic parameters were calculated. RESULTS: According to the results of electrophoresis, 5 people carried ALDH2*1/*1 as wild group and 9 people carried ALDH2*1/*2 as mutation group. The good linear range of alcohol and acetaldehyde were 0-1 570.7 microg/mL and 0-5.1772 microg/mL, respectively. The AUC values of alcohol and acetaldehyde and the t1/2Z value of alcohol were higher in the mutation group than that in the wild group. But the CL/F value of alcohol was lower in the mutation group than that in the wild group (P<0.05). CONCLUSION After the consumption of alcohol, alcohol and acetaldehyde metabolism in blood slow down in ALDH2*1/*2 mutation group influenced by the inhibition of enzyme activity, leading to the accumulation of acetaldehyde in peripheral blood, thus reinforcing their effects in the body.
Alcohol Drinking ; Aldehyde Dehydrogenase/genetics* ; Aldehyde Dehydrogenase, Mitochondrial ; Ethanol/metabolism* ; Genotype ; Humans ; Polymerase Chain Reaction ; Polymorphism, Genetic

Bacillus sp. TSH1 is a butanol-producing microorganism newly isolated in our laboratory; it can grow and ferment under facultative anaerobic conditions, while sharing similar fermentation pathways and products with Clostridium acetobutylicum. To illustrate the relationships between the products and the enzyme activities in Bacillus sp. TSH1, key butanol- and ethanol-forming enzymes were studied, including butyraldehyde dehydrogenase, butanol dehydrogenase and alcohol dehydrogenase. The activities of the three enzymes increased rapidly after the initiation of fermentation. Activities of three enzymes peaked before 21 h, and simultaneously, product concentrations also began to increase gradually. The maximum activity of alcohol dehydrogenase was 0.054 U/mg at 12 h, butyraldehyde dehydrogenase 0.035 U/mg at 21 h and butanol dehydrogenase 0.055 U/mg at 15 h. The enzyme activities then decreased, but remained constant at a low level after 24 h, while the concentrations of butanol, acetone, and ethanol continued increasing until the end of the fermentation. The results will attribute to the understanding of the butanol metabolic mechanism, and provide a reference for further study of a facultative Bacillus metabolic pathway.
Alcohol Dehydrogenase ; metabolism ; Alcohol Oxidoreductases ; metabolism ; Aldehyde Oxidoreductases ; metabolism ; Anaerobiosis ; Bacillus ; classification ; genetics ; metabolism ; Butanols ; metabolism ; Fermentation ; Metabolic Networks and Pathways

BACKGROUND/AIMS: Genetic variations of ethanol-metabolizing enzymes can affect alcohol drinking behavior. The aims of this study were to investigate and compare the distributions of these genetic polymorphisms between a healthy control group and a heavy drinker group which included an alcoholic liver cirrhosis group. METHODS: Genotypes of ADH2, ALDH2, CYP2E1, and catalase were identified by polymerase chain reaction and restriction fragment length polymorphism. Genomic DNA was extracted from peripheral leukocytes in 42 healthy controls, 12 heavy drinkers, and 30 alcoholic liver cirrhosis patients. RESULTS: 1) The genotype frequencies of ALDH2 (1*1), ADH2 (1*1), CYP2E1 (c1c1), and catalase1 (TT) were 69%, 55%, 38%, and 12%, respectively in healthy Korean males. 2) There was a significant difference in the distribution of the genetic polymorphism of ALDH2 between the control group and heavy drinker group (12 heavy drinkers and 30 alcoholic liver cirrhosis patients). The genotype frequency of ALDH2 mutant, ALDH2 (1*2) and ALDH2 (2*2) in the heavy drinker group (12%) was significantly lower than that in the control group (30%). 3) We didn't find anyone with ALDH2 homozygote mutant (DD) in the heavy drinker group. 4) There was no significant difference in the distribution of genetic polymorphisms in ADH2, CYP2E1 and catalase1 between the two groups. CONCLUSIONS: These results suggest that the absence of ALDH2 mutant genotype is strongly related to heavy drinking behavior. We can not prove, however, any evidence that the polymorphisms of other ethanol-metabolizing enzymes are associated with the determination of alcohol-drinking behavior.
Adult ; Alcohol Dehydrogenase/*genetics ; Alcohol Drinking ; Alcoholism/enzymology/*genetics ; Aldehyde Dehydrogenase/*genetics ; Cytochrome P-450 CYP2E1/*genetics ; Ethanol/metabolism ; Humans ; Liver Cirrhosis, Alcoholic/enzymology/*genetics ; Male ; Middle Aged ; *Polymorphism, Genetic

Objective To explore the change rules of blood ethanol and blood acetaldehyde concentration, the impairment of psychomotor functions of different acetaldehyde dehydrogenase （ALDH） 2 genotype individuals after alcohol consumption and the relationship among them. Methods The ALDH2 genotypes in seventy-nine healthy volunteers were obtained by SNaPshot^TM method, then divided into ALDH2*1/*1 （wild type） and ALDH2*1/*2 （mutant type） group. After volunteers consumed 1.0 g/kg of alcohol, blood ethanol concentration and blood acetaldehyde concentration at a series of time points before and after alcohol consumption and psychomotor functions, such as, visual selective response time, auditory simple response time and tracking experiment were detected. Biphasic alcohol response questionnaires were collected. Results After alcohol consumption, ALDH2*1/*2 group's blood ethanol and blood acetaldehyde concentration reached the peak earlier than ALDH2*1/*1 group. Its blood acetaldehyde concentration was higher than that of ALDH2*1/*1 group, 1-6 h after alcohol consumption. The psychomotor functions, such as visual selective response time and auditory simple response time in ALDH2*1/*2 group were more significantly impaired than those in ALDH2*1/*1 group after alcohol consumption. There was no statistical significance between the two groups in excitement or sedation reactions （P>0.05）. Pearson correlation coefficient test showed that blood acetaldehyde concentration was related with psychomotor function. Conclusion There are significant differences between the psychomotor function of ALDH2 wild type and mutant type individuals after alcohol consumption estimated to be related to the difference in blood acetaldehyde concentration after alcohol consumption.
Acetaldehyde/metabolism* ; Alcohol Drinking/blood* ; Aldehyde Dehydrogenase/genetics* ; Aldehyde Dehydrogenase, Mitochondrial ; Aldehyde Oxidoreductases ; Ethanol/metabolism* ; Genotype ; Humans ; Polymorphism, Genetic/genetics* ; Psychomotor Performance/physiology*

During epididymal transit, mammalian spermatozoa acquire new surface proteins that are necessary for gamete interaction. P34H, a member of the short-chain dehydrogenase/reductase(SDR) superfamily, is acquired on the acrosomal cap of human spermatozoon during its maturation arising within epididymis. P34H has been shown to be involved in sperm-zona pellucida interaction. Research revealed that the occurrence of low concentration of sperm protein P34H were significant amongst the idiopathic infertile male population and P34H protein could also be considered as a marker of epididymal sperm maturation in human. Therefore the level of sperm protein P34H is proposed to be a auxiliary diagnostic tool for male infertility. This paper reviews the molecular properties and regulation of the expression of P34H and its association with male reproduction.
Acyl-CoA Dehydrogenase ; Fatty Acid Desaturases ; chemistry ; Gene Expression ; Humans ; Male ; Proteins ; genetics ; physiology ; Sperm Maturation ; physiology ; Sugar Alcohol Dehydrogenases

Alcohol is oxidized to acetaldehyde by alcohol dehydrogenase (ADH) and cytochrome P-4502E1 (CYP2E1), and then to acetate by aldehyde dehydrogenase (ALDH). Polymorphisms of these ethanol-metabolizing enzymes may be associated with inter-individual difference in alcohol metabolism and susceptibility to alcoholic liver disease. We determined genotype and allele frequencies of ALDH2, CYP2E1, ADH2, and ADH3 in male Korean patients with alcoholic cirrhosis (n=56), alcoholics without evidence of liver disease (n=52), and nondrinkers (n=64) by using PCR or PCR-directed mutagenesis followed by restriction enzyme digestion. The prevalences of heterozygous ALDH2*1/*2 plus homozygous ALDH2*2/*2 in patients with alcoholic cirrhosis (7.1%) and alcoholics without evidence of liver disease (3.8%) were significantly lower than that in nondrinkers (45.3%). The c2 allele frequencies of the CYP2E1 in alcoholic cirrhosis, alcoholics without evidence of liver disease, and nondrinkers were 0.21, 0.20, and 0.20, respectively. Allele frequencies of ADH2*2 in the three groups were 0.78, 0.74, and 0.77 and those of ADH3*1 were 0.94, 0.98, and 0.95. Therefore, we confirmed the observation that the ALDH2*2 gene protects against the development of alcoholism. However, the development of cirrhosis in Korean alcoholic patients was not associated with polymorphisms of ethanol-metabolizing enzymes.
Adult ; Alcohol Dehydrogenase/*genetics ; Alcoholism/enzymology/genetics ; Aldehyde Dehydrogenase/*genetics ; Central Nervous System Depressants/pharmacokinetics ; Cytochrome P-450 CYP2E1/*genetics ; Ethanol/pharmacokinetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Human ; Korea ; Liver Cirrhosis, Alcoholic/enzymology/*genetics ; Male ; Middle Age ; *Polymorphism (Genetics)

BACKGROUND/AIMS: Susceptibility to organ damage induced by alcohol may be related to inherited variations (polymorphisms) in alcohol-metabolizing enzymes, or polymorphisms affecting cytokines. The aim of this study was to compare the genotype and allelic frequencies of ADH2, ADH3, ALDH2, cytochrome P450-2E1, IL-1, IL-6, IL-8 and tumor necrosis factor-alpha in patients with alcoholic pancreatitis and alcoholic liver cirrhosis with those of controls. METHODS: We determined the polymorphism of genes of the above-mentioned alcohol-metabolizing enzymes and cytokines in 29 alcoholic pancreatitis patients (AP), 22 alcoholic liver cirrhosis patients (LC) and 100 healthy blood donors (control). The genotypes were characterized by restriction fragment length polymorphism after amplification of genomic DNA by polymerase chain reaction. RESULTS: The allelic frequency of CYP2E1*c2 was significantly different in three groups (AP: LC: Control=0.224: 0.136: 0.320, p<0.05). There was no significant difference in the other genotypes or allelic frequencies of the three groups. The allelic frequencies of CYP2E1*c2 and ALDH2*2 were more frequent in the control than patients with alcoholic liver cirrhosis (LC: Control=0.136: 0.320, p<0.05, LC: Control= 0.114: 0.265, p<0.05). Allelic frequencies of ADH2 was statisitcally different between LC and control (ADH2*1; LC: Control=0.727: 0.495, ADH2*2; 0.227: 0.360, ADH2*3; 0.046: 0.145, p<0.05). CONCLUSIONS: There was no difference in the frequencies of genotype and allele of enzymes and cytokines among the three groups. However, frequency of ADH2*1 was significantly higher and those of CYP2E1*c2 and ALDH2*2 were significantly lower than LC group than control.
Adult ; Aged ; Alcohol Dehydrogenase/*genetics ; Aldehyde Dehydrogenase/*genetics ; Cytochrome P-450 CYP2E1/genetics ; Cytokines/*genetics ; English Abstract ; Female ; Gene Frequency ; Genotype ; Humans ; Liver Cirrhosis, Alcoholic/*genetics ; Male ; Middle Aged ; Pancreatitis, Alcoholic/*genetics ; *Polymorphism, Genetic

OBJECTIVETo explore the relationship between genetic polymorphisms of the ethanol metabolizing enzymes and the occurrence of alcoholic liver disease (ALD).

METHODSSixty-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.

RESULTSThe 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.

CONCLUSIONSPolymorphic 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 ; genetics ; Aldehyde Oxidoreductases ; genetics ; Genotype ; Humans ; Isoenzymes ; genetics ; Liver Diseases, Alcoholic ; genetics ; Male ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Genetic

The 1,3-propanediol oxidoreductase isoenzyme encoding gene (yqhD) from E. coli was amplified by PCR. yqhD was inserted in pEtac to yield the recombinant expression vector pEtac-yqhD. Over-expression of yqhD in E. coli JM109 was achieved with pEtac-yqhD. SDS-PAGE analysis showed an over-expressed recombinant product at about 43 kD, consistent with the molecular weight predicted from gene sequence. Compared with E. coli JM109 (pEtac), the 1,3-propanediol oxidoreductase isoenzyme activity of the recombinant E. coli (pEtac-yqhD) reached 120 u/mg protein under the induction of 1.0 mmol/L IPTG at 37 degrees C for 4 hours; at similar conditions, enzyme activity of E. coli JM109 (pEtac) was only 0.5 u/mg protein. The recombinant E. coli JM109 (pUCtac-dhaB, pEtac-yqhD) was constructed. After induction with 1.0 mmol/L IPTG, the recombinant strain could transform 50 g/L glycerol to 38 g/L 1,3-propanediol under aerobic conditions. This work demonstrated firstly that the 1,3-propanediol oxidoreductase isoenzyme could show high activity under aerobic conditions.
Aerobiosis ; Alcohol Dehydrogenase ; Alcohol Oxidoreductases ; genetics ; metabolism ; Aldehyde Reductase ; genetics ; metabolism ; Escherichia coli ; enzymology ; genetics ; Escherichia coli Proteins ; genetics ; metabolism ; Genetic Engineering ; methods ; Isoenzymes ; Propylene Glycols ; metabolism ; Recombinant Proteins ; genetics ; metabolism