Transcript Enzyme review

Enzyme review
Made by Bushmelev Eugene
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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 lessactive encoded by ADH1B*1/*1increase the risk of esophageal squamous c
ell 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 ALD
H2 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, France
5. National Institute of Public Health, University of
Southern Denmark, Copenhagen, Denmark
References
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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)
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)
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)
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)
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
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www.gopubmed.org
www.pdb.org
www.uniprot.org/uniprot/P00558
http://www.ebi.ac.uk/pdbsum/3c39