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Contents 1 Introduction 2 Structure 3 Function 4 Mutations 5 Treatment 6 References

Introduction

Some kind of intro, where it’s located, coding gene is located on chromosome 12 (12q24.2), 44kpbs in lenght with 13 exons^[1]…

Structure

spinqualitylabelsall models Human mitochondrial aldehyde dehydrogenase, apo form (PDB entry 3N80) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Homotetramer functioning as dimer of dimers. [2]

Function

Detoxifying of toxic aldehydes, involved in many pathways such as ethanol breakdown, lipid metabolization, role in oxidative stress of cell.

Mutations

spinqualitylabelsall models Human Mitochondrial Aldehyde Dehydrogenase Asian Variant, ALDH2*2, complexed with agonist Alda-1 (PDB entry 3INL) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image There are seven mutations observed in different ethnicities with higher relative prevalence, there is more cancer issued mutations[3]. Most studied of them is East Asian mutation (ALDH2*2) connected with alcohol flushing syndrome and other diseases[2]. ALDH2*2 alcohol flushing response is semidominant, thus heterozygotic individuals show lesser phenotype. After moderate consumption of alcohol, individuals affected by alcohol suffer from heavier hangover symptoms, homozygotes, even extreme one such as tachycardia, hypotension, nausea, and vomiting. Heterozygotes have reported subjectively more intense and more pleasant rection to alcohol than individuals with ALDH2*1/2*1[4]. There are fewer people with at least one copy of ALDH2*2 who suffer from liver cirrhosis, thus is concluded that this mutation can serve as protection against excessive alcohol consumption. This fact depends on cultural differences and relationship with alcohol as the protective effect is somehow weaker in African or European populations, as there can be social pressure to drink more alcohol in social activities, even in Eastern cultures people with flushing cannot escape or reject such alcoholism[5]. ALDH2 designation Mutation Location AA change Major ethnicity Allele frequency Relative activity WT (ALDH2*1) ALDH2*2 E504K[6] 504 Glu → Lys East Asian 26.6% 0% ALDH2*3 I41V single-carbon change in the AA side chain [2] African 0.6% 60% ALDH2*4 P92T[7] 92 Pro → Thr Latino 2.5% 32% ALDH2*5 T244M[8] 244 Thr → Met South Asian 0.7% 38% ALDH2*6 V304M[9] 304 Val → Met Latino 2.4% 11% ALDH2*7 R338W[10] 338 Arg → Trp Finnish 1.2% 23%

Treatment

References

1. ↑ Wenzel P, Hink U, Oelze M, Schuppan S, Schaeuble K, Schildknecht S, Ho KK, Weiner H, Bachschmid M, Munzel T, Daiber A. Role of reduced lipoic acid in the redox regulation of mitochondrial aldehyde dehydrogenase (ALDH-2) activity. Implications for mitochondrial oxidative stress and nitrate tolerance. J Biol Chem. 2007 Jan 5;282(1):792-9. doi: 10.1074/jbc.M606477200. Epub 2006 Nov , 13. PMID:17102135 doi:http://dx.doi.org/10.1074/jbc.M606477200
2. ↑ ^{2.0 2.1 2.2} Chen CH, Ferreira JCB, Joshi AU, Stevens MC, Li SJ, Hsu JH, Maclean R, Ferreira ND, Cervantes PR, Martinez DD, Barrientos FL, Quintanares GHR, Mochly-Rosen D. Novel and prevalent non-East Asian ALDH2 variants; Implications for global susceptibility to aldehydes' toxicity. EBioMedicine. 2020 May;55:102753. doi: 10.1016/j.ebiom.2020.102753. Epub 2020 May, 8. PMID:32403082 doi:http://dx.doi.org/10.1016/j.ebiom.2020.102753
3. ↑ ALDH2 Gene - Somatic Mutations in Cancer https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=ALDH2
4. ↑ doi: https://dx.doi.org/10.1111/j.1530-0277.1992.tb01907
5. ↑ Wang Q, Chang B, Li X, Zou Z. Role of ALDH2 in Hepatic Disorders: Gene Polymorphism and Disease Pathogenesis. J Clin Transl Hepatol. 2021 Feb 28;9(1):90-98. doi: 10.14218/JCTH.2020.00104., Epub 2021 Jan 4. PMID:33604259 doi:http://dx.doi.org/10.14218/JCTH.2020.00104
6. ↑ E504K https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451499
7. ↑ P92T https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99454838
8. ↑ T244M https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99452531
9. ↑ V304M https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451318
10. ↑ R338W https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99455550