Stereospecificity of cinnamyl alcohol dehydrogenase and synthesis of stereospecifically labelled coniferyl alcohol

Using horse liver alcohol dehydrogenase, stereospecifically tritiated (R)- and (S)-(γ-3H)-coniferyl alcohol was synthesized. Using both of these substrates it was demonstrated that cinnamyl alcohol dehydrogenase from lignifying Forsythia tissue specifically removes the pro-R-hydrogen atom of coniferyl alcohol in the oxidation to the aldehyde. This also means that in the reverse reaction the A-hydrogen of NADPH is transferred to the Re-site of coniferyl aldehyde

Effect of Elaeagnus Conferta Roxb (Elaeagnaceae) Dry Fruit on the Activities of Hepatic Alcohol Dehydrogenase and Aldehyde Dehydrogenase in Mice

Purposes: To determine the effect of Elaeagnus conferta Roxb dry fruit powder (ECR) on blood alcohol clearance and on the activities of hepatic alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH).Methods: In a randomized controlled study, acute alcohol intoxication was induced in mice with Hongxing liquor containing 65 % v/v ethanol orally. The effect of ECR on blood alcohol clearance and on the activities of hepatic alcohol dehydrogenase and aldehyde dehydrogenase in the mice was then investigated.Results: A 30-min pretreatment with ECR at 400 and 800 mg/kg led to a faster clearance of blood alcohol after the alcohol ingestion. The concentration of blood alcohol at 4 h after alcohol ingestion decreased by 21.2 % in mice pretreated with 800 mg/kg ECR. The activities of hepatic alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were enhanced by ECR.Conclusion: These results suggest that pretreatment with ECR might stimulate the clearance of blood alcohol by increasing the activities of hepatic alcohol dehydrogenase and aldehyde dehydrogenase.Keywords: Elaeagnus conferta Roxb, blood alcohol clearance, alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH)

Biology, Genetics, and Environment: Underlying Factors Influencing Alcohol Metabolism.

Gene variants encoding several of the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), are among the largest genetic associations with risk for alcohol dependence. Certain genetic variants (i.e., alleles)--particularly the ADH1B*2, ADH1B*3, ADH1C*1, and ALDH2*2 alleles--have been associated with lower rates of alcohol dependence. These alleles may lead to an accumulation of acetaldehyde during alcohol metabolism, which can result in heightened subjective and objective effects. The prevalence of these alleles differs among ethnic groups; ADH1B*2 is found frequently in northeast Asians and occasionally Caucasians, ADH1B*3 is found predominantly in people of African ancestry, ADH1C*1 varies substantially across populations, and ALDH2*2 is found almost exclusively in northeast Asians. Differences in the prevalence of these alleles may account at least in part for ethnic differences in alcohol consumption and alcohol use disorder (AUD). However, these alleles do not act in isolation to influence the risk of AUD. For example, the gene effects of ALDH2*2 and ADH1B*2 seem to interact. Moreover, other factors have been found to influence the extent to which these alleles affect a person's alcohol involvement, including developmental stage, individual characteristics (e.g., ethnicity, antisocial behavior, and behavioral undercontrol), and environmental factors (e.g., culture, religion, family environment, and childhood adversity)

STUDIES ON THE PROPERTIES OF RETINAL ALCOHOL DEHYDROGENASE FROM THE RAT

An NAD-dependent alcohol dehydrogenase (alcohol:NAD oxidoreductase; EC 1.1.1.1) has been isolated and partially purified from the retinal cytosol of the rat. Its substrate specificity and sensitivity to inhibitors of hepatic alcohol dehydrogenase have been investigated. Ethanol, 1-propanol and 1-butanol served as substrates for this enzyme but the K m values were more than 100-fold higher than those reported for hepatic alcohol dehydrogenase. Methanol and retinol were unreactive with this alcohol dehydrogenase. Inhibition by pyrazole was observed but the K t was about 100-fold higher than the value observed for hepatic alcohol dehydrogenase. n -Butyraldoxime inhibited retinal alcohol dehydrogenase with a K t of 2 ΜM, a value which approximates its K t for hepatic alcohol dehydrogenase. 1, 10-Phenanthroline was ineffective as an inhibitor. Oxidation of retinol was observed in retinal homogenates in the presence of NADP but no inhibition was observed with ethanol, methanol or pyrazole. We conclude that oxidation of retinol is not catalysed by soluble retinal alcohol dehydrogenase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65178/1/j.1471-4159.1971.tb00195.x.pd

Polymorphisms in Alcohol Dehydrogenase (ADH): A case study on the effects of ADH and ALDH on alcoholism among Native American population

Genetic variations in an individual affects the way alcohol is metabolized in the body. Alcohol Dehydrogenase (ADH) and Aldehyde Dehydrogenase (ALDH) are the two known enzymes that participate in alcohol metabolism. Polymorphisms of these enzymes are reported to make one more or less susceptible to alcoholism in some ethnic groups. The current study is a review of various articles highlighting the effects of ADH and ALDH on different populations. A study of 26 Native American, 21 Inuit, and 17 caucasian ethnic groups revealed the influence of ADH and ALDH on alcohol dependence. In one of the studies, different ADH allele populations were studied and found that the presence of ADH1B*1 allele led to increase in alcoholism whereas ADH1B*2 and ADH1B*3 alleles led to decrease in alcoholism. In another study, each participant was given alcohol intravenously until their blood alcohol was at approximately 125 mg.%. The rate of metabolism was calculated using body weight, concentration of alcohol, and the time it took for blood alcohol levels to reach a desired amount. The rate of decline of alcohol metabolism among Caucasian was 0.370 mg.% per minute, Native American 0.259 mg.% per minute, and the Inuit population 0.264 mg.% per minute. The study found that the Native American and Inuit rate of decline were similar, and the alcohol metabolism is much slower than the Caucasian counterparts. ADH polymorphism affects the ability to metabolize alcohol at different rates among different ethnicities

Interaction between alcohol dehydrogenase II gene, alcohol consumption, and risk for breast cancer

MaeIII Restriction Fragment Length Polymorphism in exon 3 of the alcohol dehydrogenase II was assessed in serum from 467 randomly selected German women and 278 women with invasive breast cancer to evaluate the interaction between a polymorphism of the alcohol dehydrogenase II gene, alcohol consumption and risk for breast cancer. In both groups, usual consumption of different alcoholic beverages was asked for using semiquantitative food frequency questionnaires. We used multivariable logistic regression to separately estimate the association between alcohol consumption and alcohol dehydrogenase II polymorphism in the population sample and women with breast cancer. The alcohol dehydrogenase II polymorphism was detected in 14 women from the population sample (3.0%) and in 27 women with invasive breast cancer (9.7%). Frequency of alcohol consumption was independent of the genotype in the population sample. In women with breast cancer, there was a significant inverse association between the alcohol dehydrogenase II polymorphism and frequency of alcohol consumption (adjusted case-only odds ratio over increasing frequency of alcohol consumption=0.5; P for interaction=0.02). We observed a gene-environment interaction between the alcohol dehydrogenase II polymorphism, alcohol consumption, and risk for breast cancer. Breast cancer risk associated with alcohol consumption may vary according to the alcohol dehydrogenase II polymorphism, probably due to differences in alcohol metabolism

Solution structure of a bacterial microcompartment targeting peptide and its application in the construction of an ethanol bioreactor

Targeting of proteins to bacterial microcompartments (BMCs) is mediated by an 18-amino-acid peptide sequence. Herein, we report the solution structure of the N-terminal targeting peptide (P18) of PduP, the aldehyde dehydrogenase associated with the 1,2-propanediol utilization metabolosome from Citrobacter freundii. The solution structure reveals the peptide to have a well-defined helical conformation along its whole length. Saturation transfer difference and transferred NOE NMR has highlighted the observed interaction surface on the peptide with its main interacting shell protein, PduK. By tagging both a pyruvate decarboxylase and an alcohol dehydrogenase with targeting peptides, it has been possible to direct these enzymes to empty BMCs in vivo and to generate an ethanol bioreactor. Not only are the purified, redesigned BMCs able to transform pyruvate into ethanol efficiently, but the strains containing the modified BMCs produce elevated levels of alcohol

Alcohol consumption and lifetime change in cognitive ability:a gene × environment interaction study

Studies of the effect of alcohol consumption on cognitive ability are often confounded. One approach to avoid confounding is the Mendelian randomization design. Here, we used such a design to test the hypothesis that a genetic score for alcohol processing capacity moderates the association between alcohol consumption and lifetime change in cognitive ability. Members of the Lothian Birth Cohort 1936 completed the same test of intelligence at age 11 and 70 years. They were assessed for recent alcohol consumption in later life and genotyped for a set of four single-nucleotide polymorphisms in three alcohol dehydrogenase genes. These variants were unrelated to late-life cognition or to socioeconomic status. We found a significant gene × alcohol consumption interaction on lifetime cognitive change (p = 0.007). Individuals with higher genetic ability to process alcohol showed relative improvements in cognitive ability with more consumption, whereas those with low processing capacity showed a negative relationship between cognitive change and alcohol consumption with more consumption. The effect of alcohol consumption on cognitive change may thus depend on genetic differences in the ability to metabolize alcohol

Integrating Horizontal Gene Transfer and Common Descent to Depict Evolution and Contrast It with ‘‘Common Design

Horizontal gene transfer (HGT) and common descent interact in space and time. Because events of HGT co-occur with phylogenetic evolution, it is difficult to depict evolutionary patterns graphically. Tree-like representations of life’s diversification are useful, but they ignore the significance of HGT in evolutionary history, particularly of unicellular organisms, ancestors of multicellular life. Here we integrate the reticulated-tree model, ring of life, symbiogenesis whole-organism model, and eliminative pattern pluralism to represent evolution. Using Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2), a bifunctional enzyme in the glycolytic pathway of amoeba, we illustrate how EhADH2 could be the product of both horizontally acquired features from ancestral prokaryotes (i.e. aldehyde dehydrogenase [ALDH] and alcohol dehydrogenase [ADH]), and subsequent functional integration of these enzymes into EhADH2, which is now inherited by amoeba via common descent. Natural selection has driven the evolution of EhADH2 active sites, which require specific amino acids (cysteine 252 in the ALDH domain; histidine 754 in the ADH domain), iron- and NAD1 as cofactors, and the substrates acetyl-CoA for ALDH and acetaldehyde for ADH. Alternative views invoking ‘‘common design’’ (i.e. the non-naturalistic emergence of major taxa independent from ancestry) to explain the interaction between horizontal and vertical evolution are unfounded

Benzyl Alcohol Dehydrogenase and Benzaldehyde Dehydrogenase of Acinetobacter calcoaceticus

1. Acinetobacter calcoaceticus NCIB 8250 can grow on benzyl alcohol as sole source of carbon and energy. Previous work had shown that benzyl alcohol is oxidised to benzoate by benzyl alcohol dehydrogenase and benzaldehyde dehydrogenase II. This thesis is concerned with the purification and characterisation of these two NAD+-dependent, soluble enzymes