ADH1B
Alcohol dehydrogenase 1B is an enzyme that in humans is encoded by the ADH1B gene.[2]
The protein encoded by this gene is a member of the alcohol dehydrogenase family. 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.[3]
The human gene is located on chromosome 4 in 4q22.
Previously ADH1B was called ADH2.
There are more genes in the family of alcohol and aldehyde dehydrogenase genes.
These genes are now referred to as ADH1A, ADH1C, and ADH4, ADH5, ADH6 and ADH7.[4]
Variants
A single nucleotide polymorphism (SNP) in ADH1B is rs1229984, that changes arginine to histidine at residue 47.[5]
The 'typical' variant of this has been referred to as ADH2(1) or ADH2*1 while the 'atypical' has been referred to as, e.g., ADH2(2), ADH2*2, ADH1B*47his, or ADH1B arg47-to-his.
This SNP may be related to alcohol consumption with the atypical genotype having reduced risk of alcoholism.[6]
Another SNP is Arg369Cys.[7]
Role in pathology
A marked decrease of ADH1B mRNA was detected in corneal fibroblasts taken from persons suffering from keratoconus.[8]
See also
References
External links
Further reading
- Harada S (2001). "[Classification of alcohol metabolizing enzymes and polymorphisms--specificity in Japanese]". Nihon Arukōru Yakubutsu Igakkai zasshi (Japanese journal of alcohol studies & drug dependence). 36 (2): 85–106. PMID 11398342.
- Green RF, Stoler JM (2007). "Alcohol dehydrogenase 1B genotype and fetal alcohol syndrome: a HuGE minireview.". Am. J. Obstet. Gynecol. 197 (1): 12–25. PMID 17618743. doi:10.1016/j.ajog.2007.02.028.
- Lange LG, Sytkowski AJ, Vallee BL (1976). "Human liver alcohol dehydrogenase: purification, composition, and catalytic features.". Biochemistry. 15 (21): 4687–93. PMID 9982. doi:10.1021/bi00666a023.
- Hurley TD, Bosron WF, Hamilton JA, Amzel LM (1991). "Structure of human beta 1 beta 1 alcohol dehydrogenase: catalytic effects of non-active-site substitutions.". Proc. Natl. Acad. Sci. U.S.A. 88 (18): 8149–53. PMC 52464
. PMID 1896463. doi:10.1073/pnas.88.18.8149.
- Stewart MJ, McBride MS, Winter LA, Duester G (1990). "Promoters for the human alcohol dehydrogenase genes ADH1, ADH2, and ADH3: interaction of CCAAT/enhancer-binding protein with elements flanking the ADH2 TATA box.". Gene. 90 (2): 271–9. PMID 2169444. doi:10.1016/0378-1119(90)90190-3.
- Winter LA, Stewart MJ, Shean ML, et al. (1990). "A hormone response element upstream from the human alcohol dehydrogenase gene ADH2 consists of three tandem glucocorticoid receptor binding sites.". Gene. 91 (2): 233–40. PMID 2210383. doi:10.1016/0378-1119(90)90093-7.
- Carr LG, Edenberg HJ (1990). "cis-acting sequences involved in protein binding and in vitro transcription of the human alcohol dehydrogenase gene ADH2.". J. Biol. Chem. 265 (3): 1658–64. PMID 2295648.
- Yasunami M, Kikuchi I, Sarapata D, Yoshida A (1990). "The human class I alcohol dehydrogenase gene cluster: three genes are tandemly organized in an 80-kb-long segment of the genome.". Genomics. 7 (2): 152–8. PMID 2347582. doi:10.1016/0888-7543(90)90535-3.
- Hurley TD, Edenberg HJ, Bosron WF (1990). "Expression and kinetic characterization of variants of human beta 1 beta 1 alcohol dehydrogenase containing substitutions at amino acid 47.". J. Biol. Chem. 265 (27): 16366–72. PMID 2398055.
- Carr LG, Xu Y, Ho WH, Edenberg HJ (1989). "Nucleotide sequence of the ADH2(3) gene encoding the human alcohol dehydrogenase beta 3 subunit.". Alcohol. Clin. Exp. Res. 13 (4): 594–6. PMID 2679216. doi:10.1111/j.1530-0277.1989.tb00383.x.
- Tsukahara M, Yoshida A (1989). "Chromosomal assignment of the alcohol dehydrogenase cluster locus to human chromosome 4q21-23 by in situ hybridization.". Genomics. 4 (2): 218–20. PMID 2737681. doi:10.1016/0888-7543(89)90304-2.
- Duester G, Smith M, Bilanchone V, Hatfield GW (1986). "Molecular analysis of the human class I alcohol dehydrogenase gene family and nucleotide sequence of the gene encoding the beta subunit.". J. Biol. Chem. 261 (5): 2027–33. PMID 2935533.
- Ikuta T, Szeto S, Yoshida A (1986). "Three human alcohol dehydrogenase subunits: cDNA structure and molecular and evolutionary divergence.". Proc. Natl. Acad. Sci. U.S.A. 83 (3): 634–8. PMC 322918 . PMID 2935875. doi:10.1073/pnas.83.3.634.
- Ikuta T, Fujiyoshi T, Kurachi K, Yoshida A (1985). "Molecular cloning of a full-length cDNA for human alcohol dehydrogenase.". Proc. Natl. Acad. Sci. U.S.A. 82 (9): 2703–7. PMC 397633 . PMID 2986130. doi:10.1073/pnas.82.9.2703.
- Hedén LO, Höög JO, Larsson K, et al. (1986). "cDNA clones coding for the beta-subunit of human liver alcohol dehydrogenase have differently sized 3'-non-coding regions.". FEBS Lett. 194 (2): 327–32. PMID 3000832. doi:10.1016/0014-5793(86)80111-9.
- Xu YL, Carr LG, Bosron WF, et al. (1988). "Genotyping of human alcohol dehydrogenases at the ADH2 and ADH3 loci following DNA sequence amplification.". Genomics. 2 (3): 209–14. PMID 3397059. doi:10.1016/0888-7543(88)90004-3.
PDB gallery |
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1deh: CRYSTALLIZATION OF HUMAN BETA1 ALCOHOL DEHYDROGENASE (15 MG/ML) IN 50 MM SODIUM PHOSPHATE (PH 7.5), 2.0 MM NAD+ AND 1 MM 4-IODOPYRAZOLE AT 25 OC, 13% (W/V) PEG 8000 1hdx: THREE-DIMENSIONAL STRUCTURES OF THREE HUMAN ALCOHOL DEHYDROGENASE VARIANTS: CORRELATIONS WITH THEIR FUNCTIONAL DIFFERENCES 1hdy: THREE-DIMENSIONAL STRUCTURES OF THREE HUMAN ALCOHOL DEHYDROGENASE VARIANTS: CORRELATIONS WITH THEIR FUNCTIONAL DIFFERENCES 1hdz: THREE-DIMENSIONAL STRUCTURES OF THREE HUMAN ALCOHOL DEHYDROGENASE VARIANTS: CORRELATIONS WITH THEIR FUNCTIONAL DIFFERENCES 1hso: HUMAN ALPHA ALCOHOL DEHYDROGENASE (ADH1A) 1hsz: HUMAN BETA-1 ALCOHOL DEHYDROGENASE (ADH1B*1) 1ht0: HUMAN GAMMA-2 ALCOHOL DEHYDROGENSE 1htb: CRYSTALLIZATION OF HUMAN BETA3 ALCOHOL DEHYDROGENASE (10 MG/ML) IN 100 MM SODIUM PHOSPHATE (PH 7.5), 7.5 MM NAD+ AND 1 MM 4-IODOPYRAZOLE AT 25 C 1u3t: Crystal Structure of Human Alcohol Dehydrogenase Alpha-Alpha Isoform Complexed with N-Cyclopentyl-N-Cyclobutylformamide Determined to 2.5 Angstrom Resolution 1u3u: Crystal Structure of Human Alcohol Dehydrogenase Beta-1-Beta-1 Isoform Complexed with N-Benzylformamide Determined to 1.6 Angstrom Resolution 1u3v: Crystal Structure of Human Alcohol Dehydrogenase Beta-1-Beta-1 Isoform Complexed with N-Heptylformamide Determined to 1.65 Angstrom Resolution 1u3w: Crystal Structure of Human Alcohol Dehydrogenase Gamma-2-Gamma-2 Isoform Complexed with N-1-Methylheptylformamide Determined to 1.45 Angstrom Resolution 3hud: THE STRUCTURE OF HUMAN BETA 1 BETA 1 ALCOHOL DEHYDROGENASE: CATALYTIC EFFECTS OF NON-ACTIVE-SITE SUBSTITUTIONS |
