ALDH2: Difference between revisions
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== Introduction == | == Introduction == | ||
Some kind of intro, where it’s located, coding gene is located on chromosome 12 (12q24.2), 44kpbs in lenght with 13 exons <ref>DOI:10.1074/jbc.M606477200</ref>… | Some kind of intro, where it’s located, coding gene is located on chromosome 12 (12q24.2), 44kpbs in lenght with 13 exons<ref>DOI:10.1074/jbc.M606477200</ref>… | ||
== Structure == | == Structure == | ||
<StructureSection load='3N80' size='350' side='right' caption='Human mitochondrial aldehyde dehydrogenase, apo form (PDB entry [http://doi.org/10.2210/pdb3N80/pdb 3N80])' scene=''> | <StructureSection load='3N80' size='350' side='right' caption='Human mitochondrial aldehyde dehydrogenase, apo form (PDB entry [http://doi.org/10.2210/pdb3N80/pdb 3N80])' scene=''> | ||
Homotetramer ... | Homotetramer functioning as dimer of dimers. <ref name="nov2020">DOI: 10.1016/j.ebiom.2020.102753</ref> | ||
</StructureSection> | </StructureSection> | ||
== Function == | == Function == | ||
| Line 9: | Line 9: | ||
== Mutations == | == Mutations == | ||
<StructureSection load='3INL' size='350' side='right' caption='Human Mitochondrial Aldehyde Dehydrogenase Asian Variant, ALDH2*2, complexed with agonist Alda-1 (PDB entry [http://doi.org/10.2210/pdb3INL/pdb 3INL])' scene=''> | <StructureSection load='3INL' size='350' side='right' caption='Human Mitochondrial Aldehyde Dehydrogenase Asian Variant, ALDH2*2, complexed with agonist Alda-1 (PDB entry [http://doi.org/10.2210/pdb3INL/pdb 3INL])' scene=''> | ||
There are seven mutations observed in different | There are seven mutations observed in different ethnicities with higher relative prevalence, there is more cancer issued mutations<ref>''ALDH''2 Gene - Somatic Mutations in Cancer https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=ALDH2</ref>. Most studied of them is East Asian mutation (''ALDH''2*2) connected with alcohol flushing syndrome and other diseases<ref name="nov2020"/>. ''ALDH''2*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 ''ALDH''2*1/2*1<ref>DOI:10.1111/j.1530-0277.1992.tb01907</ref>. There are fewer people with at least one copy of ''ALDH''2*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<ref>DOI:10.14218/jcth.2020.00104</ref>. | ||
{| class="wikitable" | {| class="wikitable" | ||
|- | |- | ||
! '' | ! ''ALDH''2 designation | ||
! Mutation | ! Mutation | ||
! Location | ! Location | ||
! AA change | ! AA change | ||
! Major ethnicity | ! Major ethnicity | ||
! Allele frequency | |||
! Relative activity | ! Relative activity | ||
|- | |- | ||
| '''WT ('' | | '''WT (''ALDH''2*1)''' | ||
| | | | ||
| | | | ||
| Line 27: | Line 28: | ||
| | | | ||
|- | |- | ||
| ''''' | | '''''ALDH''2*2''' | ||
| E504K <ref>E504K https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451499</ref> | | E504K<ref>E504K https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451499</ref> | ||
| 504 | | 504 | ||
| Glu → Lys<br /> | | Glu → Lys<br /> | ||
| East Asian | | East Asian | ||
| 0 % | | 26.6% | ||
| 0% | |||
|- | |- | ||
| ''''' | | '''''ALDH''2*3''' | ||
| I41V | | I41V | ||
| | | colspan="2" | single-carbon change in the AA side chain <ref name="nov2020"/> | ||
| | |||
| African | | African | ||
| 60 % | | 0.6% | ||
| 60% | |||
|- | |- | ||
| ''''' | | '''''ALDH''2*4''' | ||
| P92T <ref>P92T https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99454838</ref> | | P92T<ref>P92T https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99454838</ref> | ||
| 92 | | 92 | ||
| Pro → Thr | | Pro → Thr | ||
| Latino | | Latino | ||
| 32 % | | 2.5% | ||
| 32% | |||
|- | |- | ||
| ''''' | | '''''ALDH''2*5''' | ||
| T244M <ref>T244M https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99452531</ref> | | T244M<ref>T244M https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99452531</ref> | ||
| 244 | | 244 | ||
| Thr → Met | | Thr → Met | ||
| South Asian | | South Asian | ||
| 38 % | | 0.7% | ||
| 38% | |||
|- | |- | ||
| ''''' | | '''''ALDH''2*6''' | ||
| V304M <ref>V304M https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451318</ref> | | V304M<ref>V304M https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451318</ref> | ||
| 304 | | 304 | ||
| Val → Met | | Val → Met | ||
| Latino | | Latino | ||
| 11 %<br /> | | 2.4% | ||
| 11%<br /> | |||
|- | |- | ||
| ''''' | | '''''ALDH''2*7''' | ||
| R338W <ref>R338W https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99455550</ref> | | R338W<ref>R338W https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99455550</ref> | ||
| 338 | | 338 | ||
| Arg → Trp | | Arg → Trp | ||
| Finnish | | Finnish | ||
| 23 % | | 1.2% | ||
| 23% | |||
|} | |} | ||
</StructureSection> | </StructureSection> | ||
== | == Treatment == | ||
== References == | == References == | ||
<references/> | <references/> | ||
