ALDH2

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ALDH2

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Aldehyde dehydrogenase 2 family (mitochondrial)

PDB rendering based on 1a4z.

Available structures
PDB	1CW3, 1NZW, 1NZX, 1NZZ, 1O00, 1O01, 1O02, 1O04, 1O05, 1ZUM, 2ONM, 2ONN, 2ONO, 2ONP, 2VLE, 3INJ, 3INL

Identifiers

Symbols

ALDH2; ALDH-E2; ALDHI; ALDM; MGC1806

External IDs

OMIM: 100650 MGI: 99600 HomoloGene: 55480 GeneCards: ALDH2 Gene

EC number

1.2.1.3

Gene Ontology
Molecular function	• aldehyde dehydrogenase (NAD) activity • aldehyde dehydrogenase [NAD(P)+ activity] • electron carrier activity • oxidoreductase activity • identical protein binding
Cellular component	• mitochondrion • mitochondrial matrix
Biological process	• liver development • carbohydrate metabolic process • alcohol metabolic process • ethanol oxidation • xenobiotic metabolic process • synaptic transmission • response to lipopolysaccharide • response to progesterone stimulus • cellular response to hormone stimulus • response to testosterone stimulus • response to nicotine • neurotransmitter biosynthetic process • response to hyperoxia • cellular response to fatty acid
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 12:
112.2 – 112.25 Mb

Chr 5:
122.02 – 122.04 Mb

PubMed search

[1]

[2]

Aldehyde dehydrogenase 2 family (mitochondrial), also known as ALDH2, is a human gene found on chromosome 12.^[1]^[2]

Contents

1 Function
2 Isoforms
3 Clinical significance
4 Interactions
5 See also
6 References
7 Further reading
8 External links

Function

The enzyme encoded by this gene belongs to the aldehyde dehydrogenase family of enzymes that catalyze the chemical transformation from acetaldehyde to acetic acid. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism.

acetaldehyde
acetic acid
Chemical structure of the ALDH2 activator Alda-1.

Isoforms

Two major liver isoforms of this enzyme, cytosolic and mitochondrial, can be distinguished by their electrophoretic mobilities, kinetic properties, and subcellular localizations. The ALDH2 gene encodes a mitochondrial isoform, which has a low K_m for acetaldehydes, and is localized in mitochondrial matrix; in contrast the ALDH1 gene codes for the cytosolic isoform.^[3]

Clinical significance

Most Caucasians have two major isozymes, while approximately 50% of Asians have one normal copy of the ALDH2 gene and one mutant copy that encodes an inactive mitochondrial isoenzyme. A remarkably higher frequency of acute alcohol intoxication among Asians than among Caucasians has been repeatedly shown to be related to the very much reduced activity of the mutant ALDH2-2 isoenzyme.^[3] There has been a steady increase over the past 10 years in the number of Japanese alcoholics who manage to overcome their genetically determined aversion to alcoholism from the dominant effects of an ALDH2-2 mutation.^[4] This trend demonstrates that, even among those least likely to succumb to alcoholism, there are social pressures to drink.^[4]

An activator of ALDH2 enzymatic activity, Alda-1 (N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide), has been shown to reduce ischemia-induced cardiac damage caused by myocardial infarction.^[5]

Interactions

ALDH2 has been shown to interact with GroEL.^[6]

References

^ Yoshida A, Ikawa M, Hsu LC, Tani K (1985). "Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases". Alcohol 2 (1): 103–6. doi:10.1016/0741-8329(85)90024-2. PMID 4015823.
^ Hsu LC, Tani K, Fujiyoshi T, Kurachi K, Yoshida A (June 1985). "Cloning of cDNAs for human aldehyde dehydrogenases 1 and 2". Proc. Natl. Acad. Sci. U.S.A. 82 (11): 3771–5. doi:10.1073/pnas.82.11.3771. PMC 397869. PMID 2987944. http://www.pnas.org/content/82/11/3771.abstract.
^ ^a ^b "Entrez Gene: ALDH2 aldehyde dehydrogenase 2 family (mitochondrial)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=217.
^ ^a ^b Higuchi S, Matsushita S, Imazeki H, Kinoshita T, Takagi S, Kono H (March 1994). "Aldehyde dehydrogenase genotypes in Japanese alcoholics". Lancet 343 (8899): 741–2. doi:10.1016/S0140-6736(94)91629-2. PMID 7907720.
^ Chen C-H, Budas, GR, Churchill EN, Disatnik M-H, Hurley TD, Mochly-Rosen D (September 2008). "Activation of Aldehyde Dehydrogenase-2 Reduces Ischemic Damage to the Heart". Science 321 (5895): 1493–1495. doi:10.1126/science.1158554. PMC 2741612. PMID 18787169. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2741612.
^ Lee KH, Kim HS, Jeong HS, Lee YS (October 2002). "Chaperonin GroESL mediates the protein folding of human liver mitochondrial aldehyde dehydrogenase in Escherichia coli". Biochem. Biophys. Res. Commun. 298 (2): 216–24. doi:10.1016/S0006-291X(02)02423-3. PMID 12387818.

Yoshida A (1993). "Molecular genetics of human aldehyde dehydrogenase.". Pharmacogenetics 2 (4): 139–47. doi:10.1097/00008571-199208000-00001. PMID 1306115.
Chao YC, Liou SR, Tsai SF, Yin SJ (1994). "Dominance of the mutant ALDH2(2) allele in the expression of human stomach aldehyde dehydrogenase-2 activity.". Proc. Natl. Sci. Counc. Repub. China B 17 (3): 98–102. PMID 8290656.
Seitz HK, Meier P (2007). "The role of acetaldehyde in upper digestive tract cancer in alcoholics.". Translational research : the journal of laboratory and clinical medicine 149 (6): 293–7. doi:10.1016/j.trsl.2006.12.002. PMID 17543846.
Crabb DW, Edenberg HJ, Bosron WF, Li TK (1989). "Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant.". J. Clin. Invest. 83 (1): 314–6. doi:10.1172/JCI113875. PMC 303676. PMID 2562960. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=303676.
Hsu LC, Bendel RE, Yoshida A (1988). "Genomic structure of the human mitochondrial aldehyde dehydrogenase gene.". Genomics 2 (1): 57–65. doi:10.1016/0888-7543(88)90109-7. PMID 2838413.
Hsu LC, Tani K, Fujiyoshi T, et al. (1985). "Cloning of cDNAs for human aldehyde dehydrogenases 1 and 2.". Proc. Natl. Acad. Sci. U.S.A. 82 (11): 3771–5. doi:10.1073/pnas.82.11.3771. PMC 397869. PMID 2987944. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=397869.
Braun T, Grzeschik KH, Bober E, et al. (1986). "The structural gene for the mitochondrial aldehyde dehydrogenase maps to human chromosome 12.". Hum. Genet. 73 (4): 365–7. doi:10.1007/BF00279102. PMID 3017845.
Braun T, Bober E, Singh S, et al. (1987). "Isolation and sequence analysis of a full length cDNA clone coding for human mitochondrial aldehyde dehydrogenase.". Nucleic Acids Res. 15 (7): 3179. doi:10.1093/nar/15.7.3179. PMC 340920. PMID 3562250. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=340920.
Braun T, Bober E, Singh S, et al. (1987). "Evidence for a signal peptide at the amino-terminal end of human mitochondrial aldehyde dehydrogenase.". FEBS Lett. 215 (2): 233–6. doi:10.1016/0014-5793(87)80152-7. PMID 3582651.
Agarwal DP, Goedde HW (1987). "Human aldehyde dehydrogenase isozymes and alcohol sensitivity.". Isozymes Curr. Top. Biol. Med. Res. 16: 21–48. PMID 3610592.
Hempel J, Höög JO, Jörnvall H (1987). "Mitochondrial aldehyde dehydrogenase. Homology of putative targeting sequence to that of carbamyl phosphate synthetase I revealed by correlation of cDNA and protein data.". FEBS Lett. 222 (1): 95–8. doi:10.1016/0014-5793(87)80198-9. PMID 3653404.
Yoshida A, Ikawa M, Hsu LC, Tani K (1985). "Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases.". Alcohol 2 (1): 103–6. doi:10.1016/0741-8329(85)90024-2. PMID 4015823.
Hempel J, Kaiser R, Jörnvall H (1985). "Mitochondrial aldehyde dehydrogenase from human liver. Primary structure, differences in relation to the cytosolic enzyme, and functional correlations.". Eur. J. Biochem. 153 (1): 13–28. doi:10.1111/j.1432-1033.1985.tb09260.x. PMID 4065146.
Yoshida A, Huang IY, Ikawa M (1984). "Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals.". Proc. Natl. Acad. Sci. U.S.A. 81 (1): 258–61. doi:10.1073/pnas.81.1.258. PMC 344651. PMID 6582480. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=344651.
Xiao Q, Weiner H, Johnston T, Crabb DW (1995). "The aldehyde dehydrogenase ALDH2*2 allele exhibits dominance over ALDH2*1 in transduced HeLa cells.". J. Clin. Invest. 96 (5): 2180–6. doi:10.1172/JCI118272. PMC 185867. PMID 7593603. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=185867.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Novoradovsky A, Tsai SJ, Goldfarb L, et al. (1996). "Mitochondrial aldehyde dehydrogenase polymorphism in Asian and American Indian populations: detection of new ALDH2 alleles.". Alcohol. Clin. Exp. Res. 19 (5): 1105–10. doi:10.1111/j.1530-0277.1995.tb01587.x. PMID 8561277.
Xiao Q, Weiner H, Crabb DW (1997). "The mutation in the mitochondrial aldehyde dehydrogenase (ALDH2) gene responsible for alcohol-induced flushing increases turnover of the enzyme tetramers in a dominant fashion.". J. Clin. Invest. 98 (9): 2027–32. doi:10.1172/JCI119007. PMC 507646. PMID 8903321. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=507646.

PDB gallery

1a4z: ALDEHYDE DEHYDROGENASE FROM BOVINE MITOCHONDRIA COMPLEX WITH NAD (REDUCED) AND SAMARIUM (III)

1ag8: ALDEHYDE DEHYDROGENASE FROM BOVINE MITOCHONDRIA

1cw3: HUMAN MITOCHONDRIAL ALDEHYDE DEHYDROGENASE COMPLEXED WITH NAD+ AND MN2+

1nzw: Cys302Ser mutant of human mitochondrial aldehyde dehydrogenase complexed with NADH and Mg2+

1nzx: Human mitochondrial aldehyde dehydrogenase complexed with NAD+ in the presence of low Mg2+

1nzz: Human mitochondrial aldehyde dehydrogenase complexed with NADH in the presence of low Mg2+

1o00: Human mitochondrial aldehyde dehydrogenase complexed with NAD+ and Mg2+ showing dual NAD(H) conformations

1o01: Human mitochondrial aldehyde dehydrogenase complexed with crotonaldehyde, NAD(H) and Mg2+

1o02: Human mitochondrial aldehyde dehydrogenase complexed with NADH in the presence of Mg2+

1o04: Cys302Ser mutant of human mitochondrial aldehyde dehydrogenase complexed with NAD+ and Mg2+

1o05: Apo form of human mitochondrial aldehyde dehydrogenase

1of7:

1zum: Human Mitochondrial Aldehyde Dehydrogenase Asian Variant, ALDH2*2, Apo Form

2onm: Human Mitochondrial Aldehyde Dehydrogenase Asian Variant, ALDH2*2, complexed with NAD+

2onn: Arg475Gln Mutant of Human Mitochondrial Aldehyde Dehydrogenase, Apo form

2ono: Arg475Gln Mutant of Mitochondrial Aldehyde Dehydrogenase, apo form, pseudo-merohedrally twinned

2onp: Arg475Gln Mutant of Human Mitochondrial Aldehyde Dehydrogenase, complexed with NAD+

External links

MeSH ALDH2+protein,+human

This biochemistry article is a stub. You can help Wikipedia by expanding it.

v d e Aldehyde/oxo oxidoreductases (EC 1.2)

1.2.1: NAD or NADP	Aldehyde dehydrogenase: Acetaldehyde dehydrogenase (ALDH2) · Long-chain-aldehyde dehydrogenase Glyceraldehyde 3-phosphate dehydrogenase

1.2.2: cytochrome	Formate dehydrogenase (cytochrome)

1.2.3: oxygen	Aldehyde oxidase

1.2.4: disulfide	Oxoglutarate dehydrogenase · Pyruvate dehydrogenase · Branched-chain alpha-keto acid dehydrogenase complex (BCKDHA, BCKDHB, DBT, DLD)

1.2.7: iron-sulfur protein	Pyruvate synthase

B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6

v d e Mitochondrial proteins

Outer membrane	fatty acid degradation (Carnitine palmitoyltransferase I, Long fatty acyl CoA synthetase) tryptophan metabolism (Kynureninase) monoamine neurotransmitter metabolism (Monoamine oxidase)

Intermembrane space	Adenylate kinase - Creatine kinase

Inner membrane	oxidative phosphorylation (Coenzyme Q - cytochrome c reductase, Cytochrome c, NADH dehydrogenase, Succinate dehydrogenase) pyrimidine metabolism (Dihydroorotate dehydrogenase) mitochondrial shuttle (Malate-aspartate shuttle, Glycerol phosphate shuttle) other (Glutamate aspartate transporter, Glycerol-3-phosphate dehydrogenase, ATP synthase, Carnitine palmitoyltransferase II, Uncoupling protein)

Matrix	citric acid cycle (Citrate synthase, Aconitase, Isocitrate dehydrogenase, Oxoglutarate dehydrogenase, Succinyl coenzyme A synthetase, Fumarase, Malate dehydrogenase) anaplerotic reactions (Aspartate transaminase, Glutamate dehydrogenase, Pyruvate dehydrogenase complex) urea cycle (Carbamoyl phosphate synthetase I, Ornithine transcarbamylase, N-Acetylglutamate synthase) alcohol metabolism (ALDH2) PMPCB

Other/to be sorted	steroidogenesis (Cholesterol side-chain cleavage enzyme, Steroid 11-beta-hydroxylase, Aldosterone synthase), Frataxin Mitochondrial membrane transport protein (Mitochondrial permeability transition pore, Mitochondrial carrier)

Mitochondrial DNA	Complex I (MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND4L, MT-ND5, MT-ND6) - Complex III (MT-CYB) - Complex IV (MT-CO1, MT-CO2, MT-CO3) ATP synthase (MT-ATP6, MT-ATP8) tRNA (MT-TA, MT-TC, MT-TD, MT-TE, MT-TF, MT-TG, MT-TH, MT-TI, MT-TK, MT-TL1, MT-TL2, MT-TM, MT-TN, MT-TP, MT-TQ, MT-TR, MT-TS1, MT-TS2, MT-TT, MT-TV, MT-TW, MT-TY)

see also mitochondrial diseases B strc: edmb (perx), skel (ctrs), epit, cili, mito, nucl (chro)

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Wikipedia on Answers.com This article is licensed under the Creative Commons Attribution/Share-Alike License. It uses material from the Wikipedia article ALDH2. Read