ALDH2

Introduction

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

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   Print3D Homotetramer functioning as dimer of dimers.

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   Print3D There are seven mutations observed in different ethnicities with higher relative prevalence, there is more cancer issued mutations. Most studied of them is East Asian mutation (ALDH2*2) connected with alcohol flushing syndrome and other diseases. 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. 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. ALDH2 designation Mutation Location AA change Major ethnicity Allele frequency Relative activity WT (ALDH2*1) ALDH2*2 E504K 504 Glu → Lys East Asian 26.6% 0% ALDH2*3 I41V single-carbon change in the AA side chain African 0.6% 60% ALDH2*4 P92T 92 Pro → Thr Latino 2.5% 32% ALDH2*5 T244M 244 Thr → Met South Asian 0.7% 38% ALDH2*6 V304M 304 Val → Met Latino 2.4% 11% ALDH2*7 R338W 338 Arg → Trp Finnish 1.2% 23%

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Marek Földi, Michal Hub, Michal Harel