ALDH2

ALDH2
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "ALDH2".

content

Aldehyde dehydrogenase 2 family (mitochondrial)

PDB rendering based on 1a4z.

Available structures: 1a4z, 1ag8, 1cw3, 1nzw, 1nzx, 1nzz, 1o00, 1o01, 1o02, 1o04, 1o05, 1of7, 1zum, 2onm, 2onn, 2ono, 2onp

Identifiers

ALDH2; ALDH-E2; ALDHI; ALDM; MGC1806

External IDs

OMIM: 100650 MGI: 99600 HomoloGene: 55480

Gene ontology
Molecular function:	• aldehyde dehydrogenase (NAD) activity • aldehyde dehydrogenase [NAD(P)+ activity] • electron carrier activity • oxidoreductase activity
Cellular component:	• mitochondrion
Biological process:	• carbohydrate metabolic process • alcohol metabolic process • metabolic process

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

ENSG00000111275

ENSMUSG00000029455

Refseq

NM_000690 (mRNA)
NP_000681 (protein)

NM_009656 (mRNA)
NP_033786 (protein)

Location

Chr 12: 110.69 - 110.73 Mb

Chr 5: 121.83 - 121.85 Mb

Pubmed search

Aldehyde dehydrogenase 2 family (mitochondrial), also known as ALDH2, is a human gene found on chromosome 12.¹²

Contents

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

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.

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. This gene encodes a mitochondrial isoform, which has a low K_m for acetaldehydes, and is localized in mitochondrial matrix.³

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.³

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.⁴

See also

Acetaldehyde dehydrogenase

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. PMID 2987944. PMC: 397869, http://www.pnas.org/content/82/11/3771.abstract.
^ ^a ^b "Entrez Gene: ALDH2 aldehyde dehydrogenase 2 family (mitochondrial)".
^ 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.

Further reading

Yoshida A (1993). "Molecular genetics of human aldehyde dehydrogenase.". Pharmacogenetics 2 (4): 139–47. 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. PMID 2562960.
Hsu LC, Bendel RE, Yoshida A (1988). "Genomic structure of the human mitochondrial aldehyde dehydrogenase gene.". Genomics 2 (1): 57–65. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. PMID 8903321.

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 acceptor	Aldehyde dehydrogenase: Acetaldehyde dehydrogenase (ALDH2) - Long-chain-aldehyde dehydrogenase Glyceraldehyde 3-phosphate dehydrogenase

1.2.4 - disulfide acceptor	Oxoglutarate dehydrogenase - Pyruvate dehydrogenase - Branched-chain alpha-keto acid dehydrogenase complex

v • d • e Mitochondrial enzymes and transporters

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)

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)

Other/to be sorted	Cholesterol side-chain cleavage enzyme

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, MT1X)

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