ADH1B explained

Alcohol dehydrogenase 1B is an enzyme that in humans is encoded by the ADH1B gene.^{[1] [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 (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^{[3] [4]} 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.^[5]

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.^[6]

Variants

A single nucleotide polymorphism (SNP) in ADH1B is rs1229984, that changes arginine to histidine at residue 47 of the mature protein;^[7] 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.^{[8] [9] [10]} The atypical genotype produces a more active enzyme and is associated with rice domestication.^[11]

Another SNP is rs2066702 [Arg370Cys].^[12] originally called position 369. This SNP is at high frequencies in populations from Africa, and also reduces risk for alcohol dependence.^[13]

Role in pathology

A marked decrease of ADH1B mRNA was detected in corneal fibroblasts taken from persons suffering from keratoconus.^[14]

See also

• Alcohol dehydrogenase
• Aldehyde dehydrogenase

Further reading

• Harada S . [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 . April 2001 . 11398342 .
• Green RF, Stoler JM . Alcohol dehydrogenase 1B genotype and fetal alcohol syndrome: a HuGE minireview . American Journal of Obstetrics and Gynecology . 197 . 1 . 12–25 . July 2007 . 17618743 . 10.1016/j.ajog.2007.02.028 .
• Lange LG, Sytkowski AJ, Vallee BL . Human liver alcohol dehydrogenase: purification, composition, and catalytic features . Biochemistry . 15 . 21 . 4687–93 . October 1976 . 9982 . 10.1021/bi00666a023 .
• Hurley TD, Bosron WF, Hamilton JA, Amzel LM . Structure of human beta 1 beta 1 alcohol dehydrogenase: catalytic effects of non-active-site substitutions . Proceedings of the National Academy of Sciences of the United States of America . 88 . 18 . 8149–53 . September 1991 . 1896463 . 52464 . 10.1073/pnas.88.18.8149 . 1991PNAS...88.8149H . free .
• Stewart MJ, McBride MS, Winter LA, Duester G . 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 . June 1990 . 2169444 . 10.1016/0378-1119(90)90190-3 .
• Winter LA, Stewart MJ, Shean ML, Dong Y, Poellinger L, Okret S, Gustafsson JA, Duester G . 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 . July 1990 . 2210383 . 10.1016/0378-1119(90)90093-7 .
• Carr LG, Edenberg HJ . 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 . January 1990 . 10.1016/S0021-9258(19)40066-5 . 2295648 . free .
• Yasunami M, Kikuchi I, Sarapata D, Yoshida A . 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 . June 1990 . 2347582 . 10.1016/0888-7543(90)90535-3 .
• Hurley TD, Edenberg HJ, Bosron WF . 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 . September 1990 . 10.1016/S0021-9258(17)46232-6 . 2398055 . free .
• Carr LG, Xu Y, Ho WH, Edenberg HJ . Nucleotide sequence of the ADH2(3) gene encoding the human alcohol dehydrogenase beta 3 subunit . Alcoholism: Clinical and Experimental Research . 13 . 4 . 594–6 . August 1989 . 2679216 . 10.1111/j.1530-0277.1989.tb00383.x .
• Tsukahara M, Yoshida A . Chromosomal assignment of the alcohol dehydrogenase cluster locus to human chromosome 4q21-23 by in situ hybridization . Genomics . 4 . 2 . 218–20 . February 1989 . 2737681 . 10.1016/0888-7543(89)90304-2 .
• Duester G, Smith M, Bilanchone V, Hatfield GW . 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 . February 1986 . 10.1016/S0021-9258(17)35892-1 . 2935533 . free .
• Ikuta T, Szeto S, Yoshida A . Three human alcohol dehydrogenase subunits: cDNA structure and molecular and evolutionary divergence . Proceedings of the National Academy of Sciences of the United States of America . 83 . 3 . 634–8 . February 1986 . 2935875 . 322918 . 10.1073/pnas.83.3.634 . 1986PNAS...83..634I . free .
• Ikuta T, Fujiyoshi T, Kurachi K, Yoshida A . Molecular cloning of a full-length cDNA for human alcohol dehydrogenase . Proceedings of the National Academy of Sciences of the United States of America . 82 . 9 . 2703–7 . May 1985 . 2986130 . 397633 . 10.1073/pnas.82.9.2703 . 1985PNAS...82.2703I . free .
• Hedén LO, Höög JO, Larsson K, Lake M, Lagerholm E, Holmgren A, Vallee BL, Jörnvall H, von Bahr-Lindström H . 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 . January 1986 . 3000832 . 10.1016/0014-5793(86)80111-9 . 39171264 .
• Xu YL, Carr LG, Bosron WF, Li TK, Edenberg HJ . Genotyping of human alcohol dehydrogenases at the ADH2 and ADH3 loci following DNA sequence amplification . Genomics . 2 . 3 . 209–14 . April 1988 . 3397059 . 10.1016/0888-7543(88)90004-3 .

Notes and References

1. Book: Smith M . Genetics of Human Alcohol and Aldehyde Dehydrogenases . Advances in Human Genetics 15 . 15 . 249–90 . Mar 1986 . 3006456 . 10.1007/978-1-4615-8356-1_5 . 978-1-4615-8358-5 .
2. Hurley TD, Edenberg HJ . Genes encoding enzymes involved in ethanol metabolism . Alcohol Research . 34 . 3 . 339–44 . 2012 . 23134050 . 3756590 .
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 . 10.1016/S0021-9258(17)46232-6 . 2398055 . free .
4. Hurley TD, Edenberg HJ . Genes encoding enzymes involved in ethanol metabolism . Alcohol Research . 34 . 3 . 339–44 . 2012 . 23134050 . 3756590 .
5. Web site: Entrez Gene: ADH1B alcohol dehydrogenase IB (class I), beta polypeptide . 2019-12-19.
6. Hurley TD, Edenberg HJ . Genes encoding enzymes involved in ethanol metabolism . Alcohol Research . 34 . 3 . 339–44 . 2012 . 23134050 . 3756590 .
7. Matsuo Y, Yokoyama R, Yokoyama S . The genes for human alcohol dehydrogenases beta 1 and beta 2 differ by only one nucleotide . European Journal of Biochemistry . 183 . 2 . 317–20 . August 1989 . 2547609 . 10.1111/j.1432-1033.1989.tb14931.x . free .
8. Hurley TD, Edenberg HJ . Genes encoding enzymes involved in ethanol metabolism . Alcohol Research . 34 . 3 . 339–44 . 2012 . 23134050 . 3756590 .
9. Thomasson HR, Edenberg HJ, Crabb DW, Mai XL, Jerome RE, Li TK, Wang SP, Lin YT, Lu RB, Yin SJ . Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men . American Journal of Human Genetics . 48 . 4 . 677–81 . April 1991 . 2014795 . 1682953 .
10. Bierut LJ, Goate AM, Breslau N, Johnson EO, Bertelsen S, Fox L, Agrawal A, Bucholz KK, Grucza R, Hesselbrock V, Kramer J, Kuperman S, Nurnberger J, Porjesz B, Saccone NL, Schuckit M, Tischfield J, Wang JC, Foroud T, Rice JP, Edenberg HJ . ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry . Molecular Psychiatry . 17 . 4 . 445–50 . April 2012 . 21968928 . 3252425 . 10.1038/mp.2011.124 .
11. Peng . Y. . etal . 2010 . The ADH1B Arg47His polymorphism in East Asian populations and expansion of rice domestication in history . BMC Evolutionary Biology . 10 . 1 . 15 . 10.1186/1471-2148-10-15 . 20089146 . 2823730 . 2010BMCEE..10...15P . free .
12. Burnell JC, Carr LG, Dwulet FE, Edenberg HJ, Li TK, Bosron WF . 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 . 1227–33 . August 1987 . 3619918 . 10.1016/0006-291x(87)90779-0 .
13. Walters RK, Adams MJ, Adkins AE, Aliev F, Bacanu SA, Batzler A, Bertelsen S, Biernacka J, Bigdeli TB, Chen LS, Clarke TK . 6 . 2018-03-10 . Trans-ancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders. bioRxiv . en . 257311 . 10.1101/257311. free . 1871.1/c28775f1-af5b-4205-93cc-8fc89d2429b3 . free .
14. Mootha VV, Kanoff JM, Shankardas J, Dimitrijevich S . Marked reduction of alcohol dehydrogenase in keratoconus corneal fibroblasts . Molecular Vision . 15 . 706–12 . 2009 . 19365573 . 2666775 .