ADH1B

Last updated
ADH1B
Protein ADH1B PDB 1deh.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases ADH1B , ADH2, HEL-S-117, alcohol dehydrogenase 1B (class I), beta polypeptide
External IDs OMIM: 103720 HomoloGene: 133563 GeneCards: ADH1B
Orthologs
SpeciesHumanMouse
Entrez

125

n/a

Ensembl

ENSG00000196616

n/a

UniProt

P00325

n/a

RefSeq (mRNA)

NM_001286650
NM_000668

n/a

RefSeq (protein)

NP_000659
NP_001273579

n/a

Location (UCSC) Chr 4: 99.3 – 99.35 Mb n/a
PubMed search [2] n/a
Wikidata
View/Edit Human

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

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 [5] [6] 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. [7]

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 . [8]

Variants

A single nucleotide polymorphism (SNP) in ADH1B is rs1229984, that changes arginine to histidine at residue 47 of the mature protein; [9] 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. [10] [11] [12] The atypical genotype produces a more active enzyme and is associated with rice domestication. [13]

Another SNP is rs2066702 [Arg370Cys]. [14] originally called position 369. This SNP is at high frequencies in populations from Africa, and also reduces risk for alcohol dependence. [15]

Role in pathology

A marked decrease of ADH1B mRNA was detected in corneal fibroblasts taken from persons suffering from keratoconus. [16]

See also

Related Research Articles

<span class="mw-page-title-main">Alcohol dehydrogenase</span> Group of dehydrogenase enzymes

Alcohol dehydrogenases (ADH) (EC 1.1.1.1) are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NADH. In humans and many other animals, they serve to break down alcohols that are otherwise toxic, and they also participate in the generation of useful aldehyde, ketone, or alcohol groups during the biosynthesis of various metabolites. In yeast, plants, and many bacteria, some alcohol dehydrogenases catalyze the opposite reaction as part of fermentation to ensure a constant supply of NAD+.

<span class="mw-page-title-main">Acetaldehyde dehydrogenase</span> Class of enzymes

Acetaldehyde dehydrogenases are dehydrogenase enzymes which catalyze the conversion of acetaldehyde into acetyl-CoA. This can be summarized as follows:

<span class="mw-page-title-main">Alcohol tolerance</span> Bodily responses to the functional effects of ethanol in alcoholic beverages

Alcohol tolerance refers to the bodily responses to the functional effects of ethanol in alcoholic beverages. This includes direct tolerance, speed of recovery from insobriety and resistance to the development of alcohol use disorder.

<span class="mw-page-title-main">Aldehyde dehydrogenase</span> Group of enzymes

Aldehyde dehydrogenases are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes to carboxylic acids. The oxygen comes from a water molecule. To date, nineteen ALDH genes have been identified within the human genome. These genes participate in a wide variety of biological processes including the detoxification of exogenously and endogenously generated aldehydes.

Ethanol, an alcohol found in nature and in alcoholic drinks, is metabolized through a complex catabolic metabolic pathway. In humans, several enzymes are involved in processing ethanol first into acetaldehyde and further into acetic acid and acetyl-CoA. Once acetyl-CoA is formed, it becomes a substrate for the citric acid cycle ultimately producing cellular energy and releasing water and carbon dioxide. Due to differences in enzyme presence and availability, human adults and fetuses process ethanol through different pathways. Gene variation in these enzymes can lead to variation in catalytic efficiency between individuals. The liver is the major organ that metabolizes ethanol due to its high concentration of these enzymes.

<span class="mw-page-title-main">ALDH2</span> Enzyme

Aldehyde dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the ALDH2 gene located on chromosome 12. ALDH2 belongs to the aldehyde dehydrogenase family of enzymes. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. ALDH2 has a low Km for acetaldehyde, and is localized in mitochondrial matrix. The other liver isozyme, ALDH1, localizes to the cytosol.

In enzymology, a retinol dehydrogenase (RDH) (EC 1.1.1.105) is an enzyme that catalyzes the chemical reaction

In enzymology, a S-(hydroxymethyl)glutathione dehydrogenase (EC 1.1.1.284) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Formaldehyde dehydrogenase</span>

In enzymology, a formaldehyde dehydrogenase (EC 1.2.1.46) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">ADH1C</span> Protein-coding gene in the species Homo sapiens

Alcohol dehydrogenase 1C is an enzyme that in humans is encoded by the ADH1C gene.

<span class="mw-page-title-main">Formate–tetrahydrofolate ligase</span>

In enzymology, a formate—tetrahydrofolate ligase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">ADH5</span> Protein-coding gene in the species Homo sapiens

Alcohol dehydrogenase class-3 is an enzyme that in humans is encoded by the ADH5 gene.

<span class="mw-page-title-main">ADH4</span> Protein-coding gene in the species Homo sapiens

Alcohol dehydrogenase 4 is an enzyme that in humans is encoded by the ADH4 gene.

<span class="mw-page-title-main">ADH1A</span> Protein-coding gene in the species Homo sapiens

Alcohol dehydrogenase 1A is an enzyme that in humans is encoded by the ADH1A gene.

<span class="mw-page-title-main">ADH7</span> Protein-coding gene in the species Homo sapiens

Alcohol dehydrogenase class 4 mu/sigma chain is an enzyme that in humans is encoded by the ADH7 gene.

<span class="mw-page-title-main">GABRA2</span> Protein in humans

Gamma-aminobutyric acid receptor subunit alpha-2 is a protein in humans that is encoded by the GABRA2 gene.

<span class="mw-page-title-main">ADH6</span> Protein-coding gene in the species Homo sapiens

Alcohol dehydrogenase 6 is an enzyme that in humans is encoded by the ADH6 gene.

<span class="mw-page-title-main">GABRG3</span> Protein-coding gene in the species Homo sapiens

GABAA receptor-γ3, also known as GABRG3, is a protein which in humans is encoded by the GABRG3 gene.

<span class="mw-page-title-main">Short-term effects of alcohol consumption</span> Overview of the short-term effects of the consumption of alcoholic beverages

The short-term effects of alcohol consumption range from a decrease in anxiety and motor skills and euphoria at lower doses to intoxication (drunkenness), to stupor, unconsciousness, anterograde amnesia, and central nervous system depression at higher doses. Cell membranes are highly permeable to alcohol, so once it is in the bloodstream, it can diffuse into nearly every cell in the body.

<span class="mw-page-title-main">Alcohol intolerance</span> Medical condition

Alcohol intolerance is due to a genetic polymorphism of the aldehyde dehydrogenase enzyme, which is responsible for the metabolism of acetaldehyde. This polymorphism is most often reported in patients of East Asian descent. Alcohol intolerance may also be an associated side effect of certain drugs such as disulfiram, metronidazole, or nilutamide. Skin flushing and nasal congestion are the most common symptoms of intolerance after alcohol ingestion. It may also be characterized as intolerance causing hangover symptoms similar to the "disulfiram-like reaction" of aldehyde dehydrogenase deficiency or chronic fatigue syndrome. Severe pain after drinking alcohol may indicate a more serious underlying condition.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000196616 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ↑ Smith M (Mar 1986). "Genetics of Human Alcohol and Aldehyde Dehydrogenases". Advances in Human Genetics 15. Vol. 15. pp. 249–90. doi:10.1007/978-1-4615-8356-1_5. ISBN   978-1-4615-8358-5. PMID   3006456.
  4. ↑ Hurley TD, Edenberg HJ (2012). "Genes encoding enzymes involved in ethanol metabolism". Alcohol Research. 34 (3): 339–44. PMC   3756590 . PMID   23134050.
  5. ↑ 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. doi: 10.1016/S0021-9258(17)46232-6 . PMID   2398055.
  6. ↑ Hurley TD, Edenberg HJ (2012). "Genes encoding enzymes involved in ethanol metabolism". Alcohol Research. 34 (3): 339–44. PMC   3756590 . PMID   23134050.
  7. ↑ "Entrez Gene: ADH1B alcohol dehydrogenase IB (class I), beta polypeptide" . Retrieved 2019-12-19.
  8. ↑ Hurley TD, Edenberg HJ (2012). "Genes encoding enzymes involved in ethanol metabolism". Alcohol Research. 34 (3): 339–44. PMC   3756590 . PMID   23134050.
  9. ↑ 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 . PMID   2547609.
  10. ↑ Hurley TD, Edenberg HJ (2012). "Genes encoding enzymes involved in ethanol metabolism". Alcohol Research. 34 (3): 339–44. PMC   3756590 . PMID   23134050.
  11. ↑ Thomasson HR, Edenberg HJ, Crabb DW, Mai XL, Jerome RE, Li TK, Wang SP, Lin YT, Lu RB, Yin SJ (April 1991). "Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men". American Journal of Human Genetics. 48 (4): 677–81. PMC   1682953 . PMID   2014795.
  12. ↑ 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 (April 2012). "ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry". Molecular Psychiatry. 17 (4): 445–50. doi:10.1038/mp.2011.124. PMC   3252425 . PMID   21968928.
  13. ↑ Peng Y, et al. (2010). "The ADH1B Arg47His polymorphism in East Asian populations and expansion of rice domestication in history". BMC Evolutionary Biology. 10 (1): 15. Bibcode:2010BMCEE..10...15P. doi: 10.1186/1471-2148-10-15 . PMC   2823730 . PMID   20089146.
  14. ↑ 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): 1227–33. doi:10.1016/0006-291x(87)90779-0. PMID   3619918.
  15. ↑ Walters RK, Adams MJ, Adkins AE, Aliev F, Bacanu SA, Batzler A, et al. (2018-03-10). "Trans-ancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders". bioRxiv: 257311. doi: 10.1101/257311 . hdl: 1871.1/c28775f1-af5b-4205-93cc-8fc89d2429b3 .
  16. ↑ Mootha VV, Kanoff JM, Shankardas J, Dimitrijevich S (2009). "Marked reduction of alcohol dehydrogenase in keratoconus corneal fibroblasts". Molecular Vision. 15: 706–12. PMC   2666775 . PMID   19365573.

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