Summary: Iron-containing alcohol dehydrogenase
Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.
This is the Wikipedia entry entitled "Alcohol dehydrogenase". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at email@example.com and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
Alcohol dehydrogenase Edit Wikipedia article
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
Alcohol dehydrogenases (ADH) (EC 184.108.40.206) 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 otherwise are toxic, and they also participate in generation of useful aldehyde, ketone, or alcohol groups during 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+.
- 1 Evolution
- 2 Discovery
- 3 Properties
- 4 Oxidation of alcohol
- 5 Active site
- 6 Structural zinc site
- 7 Types
- 8 Applications
- 9 Clinical significance
- 10 See also
- 11 References
- 12 External links
Genetic evidence from comparisons of multiple organisms showed that a glutathione-dependent formaldehyde dehydrogenase, identical to a class III alcohol dehydrogenase (ADH-3/ADH5), is presumed to be the ancestral enzyme for the entire ADH family. Early on in evolution, an effective method for eliminating both endogenous and exogenous formaldehyde was important and this capacity has conserved the ancestral ADH-3 through time. Gene duplication of ADH-3, followed by series of mutations, the other ADHs evolved.
The ability to produce ethanol from sugar (which is the basis of how alcoholic beverages are made) is believed to have initially evolved in yeast. Though this feature is not adaptive from an energy point of view, by making alcohol in such high concentrations so that they would be toxic to other organisms, yeast cells could effectively eliminate their competition. Since rotting fruit can contain more than 4% of ethanol, animals eating the fruit needed a system to metabolize exogenous ethanol. This was thought to explain the conservation of ethanol active ADH in other species than yeast, though ADH-3 is now known to also have a major role in nitric oxide signaling.
In humans, sequencing of the ADH1B gene (responsible for production of an alcohol dehydrogenase polypeptide) shows two variants, in which there is an SNP (single nucleotide polymorphism) that leads to either a Histidine or an Arginine residue in the enzyme catalyzing the conversion of ethanol into acetaldehyde. In the Histidine variant, the enzyme is much more effective at the aforementioned conversion. The enzyme responsible for the conversion of acetaldehyde to acetate, however, remains unaffected, which leads to differential rates of substrate catalysis and causes a buildup of toxic acetaldehyde, causing cell damage. In humans, various haplotypes arising from this mutation are more concentrated in regions near Eastern China, a region also known for its low alcohol tolerance and dependence.
A study was conducted in order to find a correlation between allelic distribution and alcoholism, and the results suggest that the allelic distribution arose along with rice cultivation in the region between 12,000 and 6,000 years ago. In regions where rice was cultivated, rice was also fermented into ethanol. The results of increased alcohol availability led to alcoholism and abuse by those able to acquire it, resulting in lower reproductive fitness. Those with the variant allele have little tolerance for alcohol, thus lowering chance of dependence and abuse. The hypothesis posits that those individuals with the His variant enzyme were sensitive enough to the effects of alcohol that differential reproductive success arose and the corresponding alleles were passed through the generations.
Classical Darwinian evolution would act to select against the detrimental form of the enzyme (Arg variant) because of the lowered reproductive success of individuals carrying the allele. The result would be a higher frequency of the allele responsible for the His-variant enzyme in regions that had been under selective pressure the longest. The distribution and frequency of the His variant follows the spread of rice cultivation to inland regions of Asia, with higher frequencies of the His variant in regions that have cultivated rice the longest. The geographic distribution of the alleles seems to therefore be a result of natural selection against individuals with lower reproductive success, namely, those who carried the Arg variant allele and were more susceptible to alcoholism.
The first-ever isolated alcohol dehydrogenase (ADH) was purified in 1937 from Saccharomyces cerevisiae (brewer's yeast). Many aspects of the catalytic mechanism for the horse liver ADH enzyme were investigated by Hugo Theorell and coworkers. ADH was also one of the first oligomeric enzymes that had its amino acid sequence and three-dimensional structure determined.
The alcohol dehydrogenases comprise a group of several isozymes that catalyse the oxidation of primary and secondary alcohols to aldehydes and ketones, respectively, and also can catalyse the reverse reaction. In mammals this is a redox (reduction/oxidation) reaction involving the coenzyme nicotinamide adenine dinucleotide (NAD+).
Oxidation of alcohol
Mechanism of action in humans
- Binding of the coenzyme NAD+
- Binding of the alcohol substrate by coordination to zinc
- Deprotonation of His-51
- Deprotonation of nicotinamide ribose
- Deprotonation of Thr-48
- Deprotonation of the alcohol
- Hydride transfer from the alkoxide ion to NAD+, leading to NADH and a zinc bound aldehyde or ketone
- Release of the product aldehyde.
The mechanism in yeast and bacteria is the reverse of this reaction. These steps are supported through kinetic studies.
The substrate is coordinated to the zinc and this enzyme has two zinc atoms per subunit. One is the active site, which is involved in catalysis. In the active site, the ligands are Cys-46, Cys-174, His-67, and one water molecule. The other subunit is involved with structure. In this mechanism, the hydride from the alcohol goes to NAD+. Crystal structures indicate that the His-51 deprotonates the nicotinamide ribose, which deprotonates Ser-48. Finally, Ser-48 deprotonates the alcohol, making it an aldehyde. From a mechanistic perspective, if the enzyme adds hydride to the re face of NAD+, the resulting hydrogen is incorporated into the pro-R position. Enzymes that add hydride to the re face are deemed Class A dehydrogenases.
The active site of human ADH1 (PDB:1HSO) consists of a zinc atom, His-67, Cys-174, Cys-46, Thr-48, His-51, Ile-269, Val-292, Ala-317, and Leu-319. In the commonly studied horse liver isoform, Thr-48 is a Ser, and Leu-319 is a Phe. The zinc coordinates the substrate (alcohol). The zinc is coordinated by Cys-46, Cys-174, and His-67. Leu-319, Ala-317, His-51, Ile-269 and Val-292 stabilize NAD+ by forming hydrogen bonds. His-51 and Ile-269 form hydrogen bonds with the alcohols on nicotinamide ribose. Phe-319, Ala-317 and Val-292 form hydrogen bonds with the amide on NAD+.
Structural zinc site
Mammalian alcohol dehydrogenases also have a structural zinc site. This Zn ion plays a structural role and is crucial for protein stability. The structures of the catalytic and structural zinc sites in horse liver alcohol dehydrogenase (HLADH) as revealed in crystallographic structures, which has been studied computationally with quantum chemical as well as with classical molecular dynamics methods. The structural zinc site is composed of four closely spaced cysteine ligands (Cys97, Cys100, Cys103, and Cys111 in the amino acid sequence) positioned in an almost symmetric tetrahedron around the Zn ion. A recent study showed that the interaction between zinc and cysteine is governed by primarily an electrostatic contribution with an additional covalent contribution to the binding.
In humans, ADH exists in multiple forms as a dimer and is encoded by at least seven different genes. There are five classes (I-V) of alcohol dehydrogenase, but the hepatic form that is used primarily in humans is class 1. Class 1 consists of α, β, and γ subunits that are encoded by the genes ADH1A, ADH1B, and ADH1C. The enzyme is present at high levels in the liver and the lining of the stomach. It catalyzes the oxidation of ethanol to acetaldehyde (ethanal):
- CH3CH2OH + NAD+ → CH3CHO + NADH + H+
Another evolutionary purpose may be metabolism of the endogenous alcohol vitamin A (retinol), which generates the hormone retinoic acid, although the function here may be primarily the elimination of toxic levels of retinol.
Alcohol dehydrogenase is also involved in the toxicity of other types of alcohol: For instance, it oxidizes methanol to produce formaldehyde and ethylene glycol to ultimately yield glycolic and oxalic acids. Humans have at least six slightly different alcohol dehydrogenases. Each is a dimer (i.e., consists of two polypeptides), with each dimer containing two zinc ions Zn2+. One of those ions is crucial for the operation of the enzyme: It is located at the catalytic site and holds the hydroxyl group of the alcohol in place.
Alcohol dehydrogenase activity varies between men and women, between young and old, and among populations from different areas of the world. For example, young women are unable to process alcohol at the same rate as young men because they do not express the alcohol dehydrogenase as highly, although the inverse is true among the middle-aged. The level of activity may not be dependent only on level of expression but also on allelic diversity among the population.
Yeast and bacteria
Unlike humans, yeast and bacteria (except lactic acid bacteria, and E. coli in certain conditions) do not ferment glucose to lactate. Instead, they ferment it to ethanol and CO2. The overall reaction can be seen below:
- Glucose + 2 ADP + 2 Pi → 2 ethanol + 2 CO2 + 2 ATP + 2 H2O
In yeast and many bacteria, alcohol dehydrogenase plays an important part in fermentation: Pyruvate resulting from glycolysis is converted to acetaldehyde and carbon dioxide, and the acetaldehyde is then reduced to ethanol by an alcohol dehydrogenase called ADH1. The purpose of this latter step is the regeneration of NAD+, so that the energy-generating glycolysis can continue. Humans exploit this process to produce alcoholic beverages, by letting yeast ferment various fruits or grains. It is interesting to note that yeast can produce and consume their own alcohol.
The main alcohol dehydrogenase in yeast is larger than the human one, consisting of four rather than just two subunits. It also contains zinc at its catalytic site. Together with the zinc-containing alcohol dehydrogenases of animals and humans, these enzymes from yeasts and many bacteria form the family of "long-chain"-alcohol dehydrogenases.
Brewer's yeast also has another alcohol dehydrogenase, ADH2, which evolved out of a duplicate version of the chromosome containing the ADH1 gene. ADH2 is used by the yeast to convert ethanol back into acetaldehyde, and it is expressed only when sugar concentration is low. Having these two enzymes allows yeast to produce alcohol when sugar is plentiful (and this alcohol then kills off competing microbes), and then continue with the oxidation of the alcohol once the sugar, and competition, is gone.
In plants, ADH catalyses the same reaction as in yeast and bacteria to ensure that there is a constant supply of NAD+. Maize has two versions of ADH - ADH1 and ADH2, Arabidopsis thaliana contains only one ADH gene. The structure of Arabidopsis ADH is 47%-conserved, relative to ADH from horse liver. Structurally and functionally important residues, such as the seven residues that provide ligands for the catalytic and noncatalytic zinc atoms, however, are conserved, suggesting that the enzymes have a similar structure. ADH is constitutively expressed at low levels in the roots of young plants grown on agar. If the roots lack oxygen, the expression of ADH increases significantly. Its expression is also increased in response to dehydration, to low temperatures, and to abscisic acid, and it plays an important role in fruit ripening, seedlings development, and pollen development. Differences in the sequences of ADH in different species have been used to create phylogenies showing how closely related different species of plants are. It is an ideal gene to use due to its convenient size (2–3 kb in length with a ~1000 nucleotide coding sequence) and low copy number.
|Iron-containing alcohol dehydrogenase|
bacillus stearothermophilus glycerol dehydrogenase complex with glycerol
A third family of alcohol dehydrogenases, unrelated to the above two, are iron-containing ones. They occur in bacteria and fungi. In comparison to enzymes the above families, these enzymes are oxygen-sensitive. Members of the iron-containing alcohol dehydrogenase family include:
- Saccharomyces cerevisiae alcohol dehydrogenase 4 (gene ADH4)
- Zymomonas mobilis alcohol dehydrogenase 2 (gene adhB)
- Escherichia coli propanediol oxidoreductase EC 220.127.116.11 (gene fucO), an enzyme involved in the metabolism of fucose and which also seems to contain ferrous ion(s).
- Clostridium acetobutylicum NADPH- and NADH-dependent butanol dehydrogenases EC 1.1.1.- (genes adh1, bdhA and bdhB), enzymes that have activity using butanol and ethanol as substrates.
- E. coli adhE, an iron-dependent enzyme that harbours three different activities: alcohol dehydrogenase, acetaldehyde dehydrogenase (acetylating) EC 18.104.22.168 and pyruvate-formate-lyase deactivase.
- Bacterial glycerol dehydrogenase EC 22.214.171.124 (gene gldA or dhaD).
- Clostridium kluyveri NAD-dependent 4-hydroxybutyrate dehydrogenase (4hbd) EC 126.96.36.199
- Citrobacter freundii and Klebsiella pneumoniae 1,3-propanediol dehydrogenase EC 188.8.131.52 (gene dhaT)
- Bacillus methanolicus NAD-dependent methanol dehydrogenase EC 184.108.40.206
- E. coli and Salmonella typhimurium ethanolamine utilization protein eutG.
- E. coli hypothetical protein yiaY.
A further class of alcohol dehydrogenases belongs to quinoenzymes and requires quinoid cofactors (e.g., pyrroloquinoline quinone, PQQ) as enzyme-bound electron acceptors. A typical example for this type of enzyme is methanol dehydrogenase of methylotrophic bacteria.
In biotransformation, alcohol dehydrogenases are often used for the synthesis of enantiomerically pure stereoisomers of chiral alcohols. Often, high chemo- and enantioselectivity can be achieved. One example is the alcohol dehydrogenase from Lactobacillus brevis (LbADH), which is described to be a versatile biocatalyst. The high chemospecificity has been confirmed also in the case of substrates presenting two potential redox sites. For instance cinnamaldehyde presents both aliphatic double bond and aldehyde function. Unlike conventional catalysts, alcohol dehydrogenases are able to selectively act only on the latter, yielding exclusively cinnamyl alcohol.
In fuel cells, alcohol dehydrogenases can be used to catalyze the breakdown of fuel for an ethanol fuel cell. Scientists at Saint Louis University have used carbon-supported alcohol dehydrogenase with poly(methylene green) as an anode, with a nafion membrane, to achieve about 50 μA/cm2.
In 1949, E. Racker defined one unit of alcohol dehydrogenase activity as the amount that causes a change in optical density of 0.001 per minute under the standard conditions of assay. Recently, the international definition of enzymatic unit (E.U.) has been more common: one unit of Alcohol Dehydrogenase will convert 1.0 µmole of ethanol to acetaldehyde per minute at pH 8.8 at 25 °C.
There have been studies showing that ADH may have an influence on the dependence on ethanol metabolism in alcoholics. Researchers have tentatively detected a few genes to be associated with alcoholism. If the variants of these genes encode slower metabolizing forms of ADH2 and ADH3, there is increased risk of alcoholism. The studies have found that mutations of ADH2 and ADH3 are related to alcoholism in Northeast Asian populations. However, research continues in order to identify the genes and their influence on alcoholism.
Drug dependence is another problem associated with ADH, which researchers think might be linked to alcoholism. One particular study suggests that drug dependence has seven ADH genes associated with it. These results may lead to treatments that target these specific genes. However, more research is necessary.
Fomepizole, a drug that inhibits alcohol dehydrogenase, can be used in the setting of acute methanol or ethylene glycol toxicity. This prevents the conversion of methanol to its toxic metabolites, formic acid and formaldehyde.
- Alcohol dehydrogenase (NAD(P)+)
- Aldehyde dehydrogenase
- Blood alcohol content for rates of metabolism
- PMID 12196016. doi:10.1021/bi0257639.; Sanghani PC, Robinson H, Bosron WF, Hurley TD (September 2002). "Human glutathione-dependent formaldehyde dehydrogenase. Structures of apo, binary, and inhibitory ternary complexes". Biochemistry. 41 (35): 10778–86.
- Gutheil WG, Holmquist B, Vallee BL (Jan 1992). "Purification, characterization, and partial sequence of the glutathione-dependent formaldehyde dehydrogenase from Escherichia coli: a class III alcohol dehydrogenase". Biochemistry. 31 (2): 475–81. PMID 1731906. doi:10.1021/bi00117a025.
- Danielsson O, Jörnvall H (Oct 1992). ""Enzymogenesis": classical liver alcohol dehydrogenase origin from the glutathione-dependent formaldehyde dehydrogenase line". Proceedings of the National Academy of Sciences of the United States of America. 89 (19): 9247–51. PMC . PMID 1409630. doi:10.1073/pnas.89.19.9247.
- Persson B, Hedlund J, Jörnvall H (Dec 2008). "Medium- and short-chain dehydrogenase/reductase gene and protein families : the MDR superfamily". Cellular and Molecular Life Sciences. 65 (24): 3879–94. PMC . PMID 19011751. doi:10.1007/s00018-008-8587-z.
- Staab CA, Hellgren M, Höög JO (Dec 2008). "Medium- and short-chain dehydrogenase/reductase gene and protein families : Dual functions of alcohol dehydrogenase 3: implications with focus on formaldehyde dehydrogenase and S-nitrosoglutathione reductase activities". Cellular and Molecular Life Sciences. 65 (24): 3950–60. PMID 19011746. doi:10.1007/s00018-008-8592-2.
- Godoy L, Gonzàlez-Duarte R, Albalat R (2006). "S-Nitrosogluthathione reductase activity of amphioxus ADH3: insights into the nitric oxide metabolism". International Journal of Biological Sciences. 2 (3): 117–24. PMC . PMID 16763671. doi:10.7150/ijbs.2.117.
- Whitfield, John B. "ADH and ALDH genotypes in relation to alcohol metabolic rate and sensitivity" (PDF). Alcohol and Alcoholism.[permanent dead link]
- Peng Y, Shi H, Qi XB, Xiao CJ, Zhong H, Ma RL, Su B (2010). "The ADH1B Arg47His polymorphism in east Asian populations and expansion of rice domestication in history". BMC Evolutionary Biology. 10: 15. PMC . PMID 20089146. doi:10.1186/1471-2148-10-15.
- Eng, Mimi Y. (2007-01-01). Alcohol Research and Health. U.S. Government Printing Office. ISSN 1535-7414.
- Negelein E, Wulff HJ (1937). Biochem. Z. 293: 351.
- Theorell H, McKEE JS (Oct 1961). "Mechanism of action of liver alcohol dehydrogenase". Nature. 192 (4797): 47–50. PMID 13920552. doi:10.1038/192047a0.
- Jörnvall H, Harris JI (Apr 1970). "Horse liver alcohol dehydrogenase. On the primary structure of the ethanol-active isoenzyme". European Journal of Biochemistry / FEBS. 13 (3): 565–76. PMID 5462776. doi:10.1111/j.1432-1033.1970.tb00962.x.
- Brändén CI, Eklund H, Nordström B, Boiwe T, Söderlund G, Zeppezauer E, Ohlsson I, Akeson A (Aug 1973). "Structure of liver alcohol dehydrogenase at 2.9-angstrom resolution". Proceedings of the National Academy of Sciences of the United States of America. 70 (8): 2439–42. PMC . PMID 4365379. doi:10.1073/pnas.70.8.2439.
- Hellgren M (2009). Enzymatic studies of alcohol dehydrogenase by a combination of in vitro and in silico methods, Ph.D. thesis (PDF). Stockholm, Sweden: Karolinska Institutet. p. 70. ISBN 978-91-7409-567-8.
- Sofer W, Martin PF (1987). "Analysis of alcohol dehydrogenase gene expression in Drosophila". Annual Review of Genetics. 21: 203–25. PMID 3327463. doi:10.1146/annurev.ge.21.120187.001223.
- Hammes-Schiffer S, Benkovic SJ (2006). "Relating protein motion to catalysis". Annual Review of Biochemistry. 75: 519–41. PMID 16756501. doi:10.1146/annurev.biochem.75.103004.142800.
- Brandt EG, Hellgren M, Brinck T, Bergman T, Edholm O (Feb 2009). "Molecular dynamics study of zinc binding to cysteines in a peptide mimic of the alcohol dehydrogenase structural zinc site". Physical Chemistry Chemical Physics. 11 (6): 975–83. PMID 19177216. doi:10.1039/b815482a.
- Sultatos LG, Pastino GM, Rosenfeld CA, Flynn EJ (Mar 2004). "Incorporation of the genetic control of alcohol dehydrogenase into a physiologically based pharmacokinetic model for ethanol in humans". Toxicological Sciences. 78 (1): 20–31. PMID 14718645. doi:10.1093/toxsci/kfh057.
- Farrés J, Moreno A, Crosas B, Peralba JM, Allali-Hassani A, Hjelmqvist L, Jörnvall H, Parés X (Sep 1994). "Alcohol dehydrogenase of class IV (sigma sigma-ADH) from human stomach. cDNA sequence and structure/function relationships". European Journal of Biochemistry / FEBS. 224 (2): 549–57. PMID 7925371. doi:10.1111/j.1432-1033.1994.00549.x.
- Kovacs B, Stöppler MC. "Alcohol and Nutrition". MedicineNet, Inc. Archived from the original on 23 June 2011. Retrieved 2011-06-07.
- Duester G (Sep 2008). "Retinoic acid synthesis and signaling during early organogenesis". Cell. 134 (6): 921–31. PMC . PMID 18805086. doi:10.1016/j.cell.2008.09.002.
- Hellgren M, Strömberg P, Gallego O, Martras S, Farrés J, Persson B, Parés X, Höög JO (Feb 2007). "Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolism". Cellular and Molecular Life Sciences. 64 (4): 498–505. PMID 17279314. doi:10.1007/s00018-007-6449-8.
- Parlesak A, Billinger MH, Bode C, Bode JC (2002). "Gastric alcohol dehydrogenase activity in man: influence of gender, age, alcohol consumption and smoking in a caucasian population". Alcohol and Alcoholism. 37 (4): 388–93. PMID 12107043. doi:10.1093/alcalc/37.4.388.
- Cox, Michael; Nelson, David R.; Lehninger, Albert L (2005). Lehninger Principles of Biochemistry. San Francisco: W. H. Freeman. p. 180. ISBN 0-7167-4339-6.
- Leskovac V, Trivić S, Pericin D (Dec 2002). "The three zinc-containing alcohol dehydrogenases from baker's yeast, Saccharomyces cerevisiae". FEMS Yeast Research. 2 (4): 481–94. PMID 12702265. doi:10.1111/j.1567-1364.2002.tb00116.x.
- Coghlan A (23 December 2006). "Festive special: The brewer's tale - life". New Scientist. Archived from the original on 15 September 2008. Retrieved 2009-04-27.
- Chang C, Meyerowitz EM (Mar 1986). "Molecular cloning and DNA sequence of the Arabidopsis thaliana alcohol dehydrogenase gene". Proceedings of the National Academy of Sciences of the United States of America. 83 (5): 1408–12. PMC . PMID 2937058. doi:10.1073/pnas.83.5.1408.
- Chung HJ, Ferl RJ (Oct 1999). "Arabidopsis alcohol dehydrogenase expression in both shoots and roots is conditioned by root growth environment". Plant Physiology. 121 (2): 429–36. PMC . PMID 10517834. doi:10.1104/pp.121.2.429.
- Thompson CE, Fernandes CL, de Souza ON, de Freitas LB, Salzano FM (May 2010). "Evaluation of the impact of functional diversification on Poaceae, Brassicaceae, Fabaceae, and Pinaceae alcohol dehydrogenase enzymes". Journal of Molecular Modeling. 16 (5): 919–28. PMID 19834749. doi:10.1007/s00894-009-0576-0.
- Järvinen P, Palmé A, Orlando Morales L, Lännenpää M, Keinänen M, Sopanen T, Lascoux M (Nov 2004). "Phylogenetic relationships of Betula species (Betulaceae) based on nuclear ADH and chloroplast matK sequences". American Journal of Botany. Amjbot.org. 91 (11): 1834–45. PMID 21652331. doi:10.3732/ajb.91.11.1834. Archived from the original on 26 May 2010.
- Williamson VM, Paquin CE (Sep 1987). "Homology of Saccharomyces cerevisiae ADH4 to an iron-activated alcohol dehydrogenase from Zymomonas mobilis". Molecular & General Genetics. 209 (2): 374–81. PMID 2823079. doi:10.1007/bf00329668.
- Conway T, Sewell GW, Osman YA, Ingram LO (Jun 1987). "Cloning and sequencing of the alcohol dehydrogenase II gene from Zymomonas mobilis". Journal of Bacteriology. 169 (6): 2591–7. PMC . PMID 3584063.
- Conway T, Ingram LO (Jul 1989). "Similarity of Escherichia coli propanediol oxidoreductase (fucO product) and an unusual alcohol dehydrogenase from Zymomonas mobilis and Saccharomyces cerevisiae". Journal of Bacteriology. 171 (7): 3754–9. PMC . PMID 2661535.
- Walter KA, Bennett GN, Papoutsakis ET (Nov 1992). "Molecular characterization of two Clostridium acetobutylicum ATCC 824 butanol dehydrogenase isozyme genes". Journal of Bacteriology. 174 (22): 7149–58. PMC . PMID 1385386.
- Kessler D, Leibrecht I, Knappe J (Apr 1991). "Pyruvate-formate-lyase-deactivase and acetyl-CoA reductase activities of Escherichia coli reside on a polymeric protein particle encoded by adhE". FEBS Letters. 281 (1-2): 59–63. PMID 2015910. doi:10.1016/0014-5793(91)80358-A.
- Truniger V, Boos W (Mar 1994). "Mapping and cloning of gldA, the structural gene of the Escherichia coli glycerol dehydrogenase". Journal of Bacteriology. 176 (6): 1796–800. PMC . PMID 8132480.
- de Vries GE, Arfman N, Terpstra P, Dijkhuizen L (Aug 1992). "Cloning, expression, and sequence analysis of the Bacillus methanolicus C1 methanol dehydrogenase gene". Journal of Bacteriology. 174 (16): 5346–53. PMC . PMID 1644761.
- Leuchs S, Greiner L (2011). "Alcohol dehydrogenase from Lactobacillus brevis: A versatile catalyst for enenatioselective reduction" (PDF). CABEQ: 267–281.[permanent dead link]
- Zucca P, Littarru M, Rescigno A, Sanjust E (May 2009). "Cofactor recycling for selective enzymatic biotransformation of cinnamaldehyde to cinnamyl alcohol". Bioscience, Biotechnology, and Biochemistry. 73 (5): 1224–6. PMID 19420690. doi:10.1271/bbb.90025.
- Moore CM, Minteer SD, Martin RS (Feb 2005). "Microchip-based ethanol/oxygen biofuel cell". Lab on a Chip. 5 (2): 218–25. PMID 15672138. doi:10.1039/b412719f.
- Racker E (1950). "Crystalline alcohol dehydrogenase from baker's yeast". J. Biol. Chem. 184 (1): 313–9. PMID 15443900.
- "Enzymatic Assay of Alcohol Dehydrogenase (EC 220.127.116.11)". Sigma Aldrich. Retrieved 13 July 2015.
- Sher KJ, Grekin ER, Williams NA (2005). "The development of alcohol use disorders". Annual Review of Clinical Psychology. 1: 493–523. PMID 17716097. doi:10.1146/annurev.clinpsy.1.102803.144107.
- Luo X, Kranzler HR, Zuo L, Wang S, Schork NJ, Gelernter J (Feb 2007). "Multiple ADH genes modulate risk for drug dependence in both African- and European-Americans". Human Molecular Genetics. 16 (4): 380–90. PMC . PMID 17185388. doi:10.1093/hmg/ddl460.
- International Programme on Chemical Safety (IPCS): Methanol (PIM 335), , retrieved on March 1, 2008
- Velez LI, Shepherd G, Lee YC, Keyes DC (September 2007). "Ethylene glycol ingestion treated only with fomepizole" (PDF). J Med Toxicol. 3 (3): 125–8. PMID 18072148. doi:10.1007/BF03160922.[permanent dead link]
|Wikimedia Commons has media related to Alcohol dehydrogenase.|
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Iron-containing alcohol dehydrogenase Provide feedback
No Pfam abstract.
Internal database links
|SCOOP:||AIRC ANF_receptor DHQ_synthase Fe-ADH_2 Glyco_trans_4_4 Peripla_BP_5 Peripla_BP_6 PFK|
|Similarity to PfamA using HHSearch:||DHQ_synthase Fe-ADH_2|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001670
Alcohol dehydrogenase (EC) (ADH) catalyzes the reversible oxidation of ethanol to acetaldehyde with the concomitant reduction of NAD. Currently three, structurally and catalytically, different types of alcohol dehydrogenases are known:
- Zinc-containing 'long-chain' alcohol dehydrogenases.
- Insect-type, or 'short-chain' alcohol dehydrogenases.
- Iron-containing alcohol dehydrogenases.
Iron-containing ADH's have been found in yeast (gene ADH4) [PUBMED:3584063], as well as in Zymomonas mobilis (gene adhB) [PUBMED:2823079]. These two iron-containing ADH's are closely related to the following enzymes:
- Escherichia coli propanediol oxidoreductase (EC) (gene fucO) [PUBMED:2661535], an enzyme involved in the metabolism of fucose and which also seems to contain ferrous ion(s).
- Clostridium acetobutylicum NADPH- and NADH-dependent butanol dehydrogenases (EC) (genes adh1, bdhA and bdhB) [PUBMED:1385386], an enzyme which has activity using butanol and ethanol as substrates.
- E. coli adhE [PUBMED:2015910], an iron-dependent enzyme which harbor three different activities: alcohol dehydrogenase, acetaldehyde dehydrogenase (acetylating) (EC) and pyruvate-formate-lyase deactivase.
- Bacterial glycerol dehydrogenase (EC) (gene gldA or dhaD) [PUBMED:8132480].
- Clostridium kluyveri NAD-dependent 4-hydroxybutyrate dehydrogenase (4hbd) (EC).
- Citrobacter freundii and Klebsiella pneumoniae 1,3-propanediol dehydrogenase (EC) (gene dhaT).
- Bacillus methanolicus NAD-dependent methanol dehydrogenase (EC) [PUBMED:1644761].
- E. coli and Salmonella typhimurium ethanolamine utilization protein eutG.
- E. coli hypothetical protein yiaY.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||metal ion binding (GO:0046872)|
|oxidoreductase activity (GO:0016491)|
|Biological process||oxidation-reduction process (GO:0055114)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
If you find these logos useful in your own work, please consider citing the following article:
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Number in seed:||219|
|Number in full:||10400|
|Average length of the domain:||351.90 aa|
|Average identity of full alignment:||25 %|
|Average coverage of the sequence by the domain:||83.16 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||18|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
There is 1 interaction for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Fe-ADH domain has been found. There are 75 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
Loading structure mapping...