ALDH2

Aldehyde dehydrogenase 2 family (mitochondrial), also known as ALDH2, is a human gene found on chromosome 12.cite journal | author = Yoshida A, Ikawa M, Hsu LC, Tani K | title = Molecular abnormality and cDNA cloning of human aldehyde dehydrogenases | journal = Alcohol | volume = 2 | issue = 1 | pages = 103–6 | year = 1985 | pmid = 4015823 | doi = 10.1016/0741-8329(85)90024-2 | url = | issn = ] cite journal | author = Hsu LC, Tani K, Fujiyoshi T, Kurachi K, Yoshida A | title = Cloning of cDNAs for human aldehyde dehydrogenases 1 and 2 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 82 | issue = 11 | pages = 3771–5 | year = 1985 | month = June | pmid = 2987944 | pmc = 397869 | doi = | url = http://www.pnas.org/content/82/11/3771.abstract | issn = ]

Function

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

Isoforms

Two major liver isoforms of this enzyme, cytosolic and mitochondrial, can be distinguished by their electrophoretic mobilities, kinetic properties, and subcellular localizations. This gene encodes a mitochondrial isoform, which has a low K_m for acetaldehydes, and is localized in mitochondrial matrix.cite web | title = Entrez Gene: ALDH2 aldehyde dehydrogenase 2 family (mitochondrial)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=217| accessdate = ]

Clinical significance

Most Caucasians have two major isozymes, while approximately 50% of Asians have only the cytosolic isozyme, missing the mitochondrial isozyme. A remarkably higher frequency of acute alcohol intoxication among Asians than among Caucasians could be related to the absence of the mitochondrial isozyme.

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.cite journal | author = Chen C-H, Budas, GR, Churchill EN, Disatnik M-H, Hurley TD, Mochly-Rosen D | title = Activation of Aldehyde Dehydrogenase-2 Reduces Ischemic Damage to the Heart | journal = Science | volume = 321 | issue = 5895 | pages = 1493 - 1495 | year = 2008 | month = September | pmid = | pmc = | doi = 10.1126/science.1158554 | issn = ]

ee also

* Acetaldehyde dehydrogenase

References

Further reading

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

External links

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