ALDH2

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Aldehyde dehydrogenase 2 family (mitochondrial)

PDB rendering based on 1a4z.
Available structures
PDBOrtholog search: PDBe, RCSB
Identifiers
SymbolsALDH2; ALDH-E2; ALDHI; ALDM
External IDsOMIM100650 MGI99600 HomoloGene55480 ChEMBL: 1935 GeneCards: ALDH2 Gene
EC number1.2.1.3
RNA expression pattern
PBB GE ALDH2 201425 at tn.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez21711669
EnsemblENSG00000111275ENSMUSG00000029455
UniProtP05091P47738
RefSeq (mRNA)NM_000690NM_009656
RefSeq (protein)NP_000681NP_033786
Location (UCSC)Chr 12:
112.2 – 112.25 Mb
Chr 5:
121.57 – 121.59 Mb
PubMed search[1][2]
 
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Aldehyde dehydrogenase 2 family (mitochondrial)

PDB rendering based on 1a4z.
Available structures
PDBOrtholog search: PDBe, RCSB
Identifiers
SymbolsALDH2; ALDH-E2; ALDHI; ALDM
External IDsOMIM100650 MGI99600 HomoloGene55480 ChEMBL: 1935 GeneCards: ALDH2 Gene
EC number1.2.1.3
RNA expression pattern
PBB GE ALDH2 201425 at tn.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez21711669
EnsemblENSG00000111275ENSMUSG00000029455
UniProtP05091P47738
RefSeq (mRNA)NM_000690NM_009656
RefSeq (protein)NP_000681NP_033786
Location (UCSC)Chr 12:
112.2 – 112.25 Mb
Chr 5:
121.57 – 121.59 Mb
PubMed search[1][2]

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

Function[edit]

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.

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Metabolism of alcohol (ethanol) to acetaldehyde (ethanal) and then acetic acid (ethanoic acid)

Isoforms[edit]

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 Km for acetaldehydes, and is localized in mitochondrial matrix; in contrast the ALDH1 gene codes for the cytosolic isoform.[3]

Clinical significance[edit]

Most Europeans have two major isozymes, while approximately 50% of Northeast 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 Northeast Asians than among Europeans 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[edit]

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

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ Hsu LC, Tani K, Fujiyoshi T, Kurachi K, Yoshida A (June 1985). "Cloning of cDNAs for human aldehyde dehydrogenases 1 and 2". Proceedings of the National Academy of Sciences of the United States of America 82 (11): 3771–5. doi:10.1073/pnas.82.11.3771. PMC 397869. PMID 2987944. 
  3. ^ a b "Entrez Gene: ALDH2 aldehyde dehydrogenase 2 family (mitochondrial)". 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. 


Further reading[edit]

  • 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. 
  • 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.". Proceedings of the National Academy of Sciences of the United States of America 82 (11): 3771–5. doi:10.1073/pnas.82.11.3771. PMC 397869. PMID 2987944. 
  • 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. 
  • 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.". Proceedings of the National Academy of Sciences of the United States of America 81 (1): 258–61. doi:10.1073/pnas.81.1.258. PMC 344651. PMID 6582480. 
  • 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. 
  • 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. 

External links[edit]