enzyme review

Enzyme review Made by Bushmelev Eugene

Common • Name: Alcohol dehydrogenase 1B (ADH1B)• Code: EC 1.1.1.1• Organism: Homo Sapiens • Classification: Oxidoreductase • Structural weight: 39855 • Sequence status: complete

Annotation• Members of this enzyme family metabolize a wide variety of

substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. This encoded protein, consisting of several homo- and heterodimers of alpha, beta, and gamma subunits, exhibits high activity for ethanol oxidation and plays a major role in ethanol catabolism. Three genes encoding alpha, beta and gamma subunits are tandemly organized in a genomic segment as a gene cluster.

• Catalytic activity: An alcohol + NAD+ = an aldehyde or ketone + NADH

Pic 1 – Graphic reaction

Substrates

• primary alcohol (Etanol)

Pic 2 – Strucrure of etanol

Pic 3 – A 3D-balls diagram of etanol

Substrates • secondary alcohol ((R)-Benzoin)

Pic 4 – Strucrure of (R)-Benzoin

Pic 5 – A 3D-balls diagram of (R)-Benzoin

Pic 6 – LIGPLOT of interactions involving ligand

Structure of ADH1B

Pic 7 – Secondary structure

Structure of ADH1B

Pic 8 – Globular structure

Pic 9 – A skeleton diagram Pic 10 – A space filling diagram

Is it useful? Disease relevance of ADH1B

• The inactive ALDH2 encoded by ALDH2*1/*2 and the less-active encoded by ADH1B*1/*1increase the risk of esophageal squamous cell carcinoma

• Alcohol dehydrogenase 1Bbreast cancer risk by age 50 years in a German• Likewise, the proportion of persons with positive results for differed signifi

cantly dependingon the in both the ALDH2(1)/ALDH2(1) and ALDH2(1)/ALDH2(2)

• On the other hand, there were significant differences in the ADH2 and ALDH2 polymorphisms between healthy controls and esophageal cancer patients.

• Promoter activity of human ADH3, but not ADH1 or ADH2, was shown to be activated byretinoic acid in transient tranfection assays of Hep3B human hepatoma cells.

Analytical, diagnostic and therapeutic context of ADH1B

• Genotoxic effects of alcohol in human peripheral lymphocytes modulated by ADH1B andALDH2 gene polymorphisms.

• Therefore, we determined the genotypes of the ADH2, ADH3, and ALDH2 loci of alcoholic and nonalcoholic Chinese men living in Taiwan, using leukocyte DNA amplified by the PCR and allele-specific oligonucleotides .

• ADH2 promoter DNA fragments containing various lengths of 5'-flanking sequences were fused upstream from the gene encoding chloramphenicol acetyltransferase (cat) and transfected into the HepG2 human hepatoma cell line.

• While fibroblasts cultured from a skin biopsy from one Japanese individual revealed a heterodimer (ADH2 2-1) of alcohol dehydrogenase, skin extract from another Japanese showed a homodimer (ADH2 2-2).

• The influences of estimated body water, recent drinking history, recent smoking history, polymorphism at the ADH2 and ADH3 loci, family history of alcoholism, and percentageNative American heritage on alcohol elimination rate were determined using multipleregression analyses .

Methods

• PCR; • Amplification; • Cloning;

Publications

Pic 11 – Publications from Gopubmed

World map

Pic 12 – Worldmap from Gopubmed

Universities and academies

1. Indiana University School of Medicine and the Richard Roudebush Veteran's Affairs Medical Center, Indianapolis, Indiana, USA.

2. Shenyang Pharmaceutical University, Shenyang, China.

3. King's Health Partners, Guy's Hospital, London , UK 4. International Agency for Research on Cancer

(IARC), Lyon, France5. National Institute of Public Health, University of

Southern Denmark, Copenhagen, Denmark

References 1. Genetic polymorphisms of alcohol and aldehyde dehydrogenases, and drinking,

smoking and diet in Japanese men with oral and pharyngeal squamous cell carcinoma. Asakage, T., Yokoyama, A., Haneda, T., Yamazaki, M., Muto, M., Yokoyama, T., Kato, H., Igaki, H., Tsujinaka, T., Kumagai, Y., Yokoyama, M., Omori, T., Watanabe, H. Carcinogenesis (2007)

2. No alcoholism-protection effects of ADH1B*2 allele in antisocial alcoholics among Han Chinese in Taiwan. Lu, R.B., Ko, H.C., Lee, J.F., Lin, W.W., Huang, S.Y., Wang, T.J., Wu, Y.S., Lu, T.E., Chou, Y.H. Alcohol. Clin. Exp. Res. (2005)

3. Genotoxic effects of alcohol in human peripheral lymphocytes modulated by ADH1B and ALDH2 gene polymorphisms. Ishikawa, H., Ishikawa, T., Yamamoto, H., Fukao, A., Yokoyama, K. Mutat. Res. (2007)

4. Interactive effects of lifetime alcohol consumption and alcohol and aldehyde dehydrogenase polymorphisms on esophageal cancer risks. Chen, Y.J., Chen, C., Wu, D.C., Lee, C.H., Wu, C.I., Lee, J.M., Goan, Y.G., Huang, S.P., Lin, C.C., Li, T.C., Chou, Y.P., Wu, M.T. Int. J. Cancer (2006)

5. Alcohol elimination in Native American Mission Indians: an investigation of interindividual variation. Wall, T.L., Garcia-Andrade, C., Thomasson, H.R., Cole, M., Ehlers, C.L. Alcohol. Clin. Exp. Res. (1996)

Other references

• www.gopubmed.org• www.pdb.org• www.uniprot.org/uniprot/P00558• http://www.ebi.ac.uk/pdbsum/3c39