Alcohol dehydrogenase 1B is an enzyme that in humans is encoded by the ADH1Bgene.[5][6]
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 (beverage alcohol), retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. The encoded protein, known as ADH1B or beta-ADH, can form homodimers and heterodimers with ADH1A and ADH1C subunits, exhibits high activity for ethanol oxidation[7][8] and plays a major role in ethanol catabolism (oxidizing ethanol into acetaldehyde). The acetaldehyde is further metabolized to acetate by aldehyde dehydrogenase genes. Three genes encoding the closely related alpha, beta and gamma subunits are tandemly organized in a genomic segment as a gene cluster.[9]
The human gene is located on chromosome 4 in 4q22.
Previously ADH1B was called ADH2. There are more genes in the family of alcohol dehydrogenase. These genes are now referred to as ADH1A, ADH1C, and ADH4, ADH5, ADH6 and ADH7.[10]
Variants
A single nucleotide polymorphism (SNP) in ADH1B is rs1229984, that changes arginine to histidine at residue 47 of the mature protein;[11] standard nomenclature now includes the initiating methionine, so the position is officially 48. 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*48His. This SNP is associated with the risk for alcohol dependence, alcohol use disorders and alcohol consumption, with the atypical genotype having reduced risk of alcoholism.[12][13][14]
Another SNP is rs2066702 [Arg370Cys].[15] originally called position 369. This SNP is at high frequencies in populations from Africa, and also reduces risk for alcohol dependence.[16]
^Matsuo Y, Yokoyama R, Yokoyama S (August 1989). "The genes for human alcohol dehydrogenases beta 1 and beta 2 differ by only one nucleotide". European Journal of Biochemistry. 183 (2): 317–20. doi:10.1111/j.1432-1033.1989.tb14931.x. PMID2547609.
^Burnell JC, Carr LG, Dwulet FE, Edenberg HJ, Li TK, Bosron WF (August 1987). "The human beta 3 alcohol dehydrogenase subunit differs from beta 1 by a Cys for Arg-369 substitution which decreases NAD(H) binding". Biochemical and Biophysical Research Communications. 146 (3): 1127–33. PMID3619918.
Harada S (April 2001). "[Classification of alcohol metabolizing enzymes and polymorphisms--specificity in Japanese]". Nihon Arukoru Yakubutsu Igakkai Zasshi=Japanese Journal of Alcohol Studies & Drug Dependence. 36 (2): 85–106. PMID11398342.
Stewart MJ, McBride MS, Winter LA, Duester G (June 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. doi:10.1016/0378-1119(90)90190-3. PMID2169444.
Winter LA, Stewart MJ, Shean ML, Dong Y, Poellinger L, Okret S, Gustafsson JA, Duester G (July 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. doi:10.1016/0378-1119(90)90093-7. PMID2210383.
Carr LG, Edenberg HJ (January 1990). "cis-acting sequences involved in protein binding and in vitro transcription of the human alcohol dehydrogenase gene ADH2". The Journal of Biological Chemistry. 265 (3): 1658–64. PMID2295648.
Yasunami M, Kikuchi I, Sarapata D, Yoshida A (June 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. doi:10.1016/0888-7543(90)90535-3. PMID2347582.
Hurley TD, Edenberg HJ, Bosron WF (September 1990). "Expression and kinetic characterization of variants of human beta 1 beta 1 alcohol dehydrogenase containing substitutions at amino acid 47". The Journal of Biological Chemistry. 265 (27): 16366–72. PMID2398055.
Carr LG, Xu Y, Ho WH, Edenberg HJ (August 1989). "Nucleotide sequence of the ADH2(3) gene encoding the human alcohol dehydrogenase beta 3 subunit". Alcoholism, Clinical and Experimental Research. 13 (4): 594–6. doi:10.1111/j.1530-0277.1989.tb00383.x. PMID2679216.
Tsukahara M, Yoshida A (February 1989). "Chromosomal assignment of the alcohol dehydrogenase cluster locus to human chromosome 4q21-23 by in situ hybridization". Genomics. 4 (2): 218–20. doi:10.1016/0888-7543(89)90304-2. PMID2737681.
Duester G, Smith M, Bilanchone V, Hatfield GW (February 1986). "Molecular analysis of the human class I alcohol dehydrogenase gene family and nucleotide sequence of the gene encoding the beta subunit". The Journal of Biological Chemistry. 261 (5): 2027–33. PMID2935533.
Hedén LO, Höög JO, Larsson K, Lake M, Lagerholm E, Holmgren A, Vallee BL, Jörnvall H, von Bahr-Lindström H (January 1986). "cDNA clones coding for the beta-subunit of human liver alcohol dehydrogenase have differently sized 3'-non-coding regions". FEBS Letters. 194 (2): 327–32. doi:10.1016/0014-5793(86)80111-9. PMID3000832.
Xu YL, Carr LG, Bosron WF, Li TK, Edenberg HJ (April 1988). "Genotyping of human alcohol dehydrogenases at the ADH2 and ADH3 loci following DNA sequence amplification". Genomics. 2 (3): 209–14. doi:10.1016/0888-7543(88)90004-3. PMID3397059.
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
