ALDH2
From Proteopedia
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== 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 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"/>. | + | 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"/>. |
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{| class="wikitable" | {| class="wikitable" | ||
|- | |- | ||
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|- | |- | ||
| '''''ALDH''2*2''' | | '''''ALDH''2*2''' | ||
| - | | E504K<ref>E504K https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451499</ref> | + | | E504K<ref>Mutation overview page ALDH2 - p.E504K (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451499</ref> |
| 504 | | 504 | ||
| Glu → Lys<br /> | | Glu → Lys<br /> | ||
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|- | |- | ||
| '''''ALDH''2*4''' | | '''''ALDH''2*4''' | ||
| - | | P92T<ref>P92T https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99454838</ref> | + | | P92T<ref>Mutation overview page ALDH2 - p.P92T (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99454838</ref> |
| 92 | | 92 | ||
| Pro → Thr | | Pro → Thr | ||
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|- | |- | ||
| '''''ALDH''2*5''' | | '''''ALDH''2*5''' | ||
| - | | T244M<ref>T244M https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99452531</ref> | + | | T244M<ref>Mutation overview page ALDH2 - p.T244M (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99452531</ref> |
| 244 | | 244 | ||
| Thr → Met | | Thr → Met | ||
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|- | |- | ||
| '''''ALDH''2*6''' | | '''''ALDH''2*6''' | ||
| - | | V304M<ref>V304M https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451318</ref> | + | | V304M<ref>Mutation overview page ALDH2 - p.V304M (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451318</ref> |
| 304 | | 304 | ||
| Val → Met | | Val → Met | ||
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|- | |- | ||
| '''''ALDH''2*7''' | | '''''ALDH''2*7''' | ||
| - | | R338W<ref>R338W https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99455550</ref> | + | | R338W<ref>Mutation overview page ALDH2 - p.R338W (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99455550</ref> |
| 338 | | 338 | ||
| Arg → Trp | | Arg → Trp | ||
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| 23% | | 23% | ||
|} | |} | ||
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| + | == Alcohol liver disease == | ||
| + | |||
| + | ''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.x</ref>. There are fewer people with at least one copy of ''ALDH''2*2 who suffer from liver cirrhosis. Therefore, is concluded that this mutation can serve as protection against alcohol abuse. 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 name="HP">DOI:10.14218/jcth.2020.00104</ref>. Generally, individuals with the ALDH2 polymorphism experience less hepatic oxidative stress due to lesser alcohol consumption, by cumulating unprocessed acetaldehyde. Consequently, artificial regulation of ALH2 may be used as potential therapeutic intervention for alcoholism <ref>DOI:10.1073/ pnas.1908137116</ref>. | ||
</StructureSection> | </StructureSection> | ||
| + | |||
| + | == Non-alcoholic liver diseases == | ||
| + | Although ALHD2 misfunction can play a protective role against, on the other hand, it can increase the number of non-alcoholic fatty liver disease (NAFLD) among carriers of ALDH2*2. This can be the result of the missing ALDH2 enzyme for preserving mitochondrial respiratory function or for the cleavage of aldehydes, which can be byproducts of fat metabolism<ref name="HP"/>. . | ||
| + | |||
| + | There are concerns about metabolic interaction between retinol and ethanol metabolism. As I can result in inhibition of immunological feedback to some viral infections such as viral hepatitis. Among ALDH2*2 patients has increased probability of developing liver cirrhosis<ref name="HP"/>. | ||
| + | |||
| + | Hepatocellular carcinoma is suspected of connection with ALHD2 deficiency as it could be result of habitual alcohol drinking, non-alcoholic fatty liver disease or HBV. Due to the oxidative base of ethanol metabolism and the occurrence of the ALDH2 enzyme in mitochondria, is cocluded a correlation between low ALDH2 activity and liver cancer<ref name="HP"/>. | ||
| + | |||
== Treatment == | == Treatment == | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 21:24, 27 April 2022
Contents |
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
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Function
Detoxifying of toxic aldehydes, involved in many pathways such as ethanol breakdown, lipid metabolization, role in oxidative stress of cell.
Mutations
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Non-alcoholic liver diseases
Although ALHD2 misfunction can play a protective role against, on the other hand, it can increase the number of non-alcoholic fatty liver disease (NAFLD) among carriers of ALDH2*2. This can be the result of the missing ALDH2 enzyme for preserving mitochondrial respiratory function or for the cleavage of aldehydes, which can be byproducts of fat metabolism[10]. .
There are concerns about metabolic interaction between retinol and ethanol metabolism. As I can result in inhibition of immunological feedback to some viral infections such as viral hepatitis. Among ALDH2*2 patients has increased probability of developing liver cirrhosis[10].
Hepatocellular carcinoma is suspected of connection with ALHD2 deficiency as it could be result of habitual alcohol drinking, non-alcoholic fatty liver disease or HBV. Due to the oxidative base of ethanol metabolism and the occurrence of the ALDH2 enzyme in mitochondria, is cocluded a correlation between low ALDH2 activity and liver cancer[10].
Treatment
References
- ↑ 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
- ↑ 2.0 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
- ↑ ALDH2 Gene - Somatic Mutations in Cancer https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=ALDH2
- ↑ Mutation overview page ALDH2 - p.E504K (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451499
- ↑ Mutation overview page ALDH2 - p.P92T (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99454838
- ↑ Mutation overview page ALDH2 - p.T244M (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99452531
- ↑ Mutation overview page ALDH2 - p.V304M (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99451318
- ↑ Mutation overview page ALDH2 - p.R338W (Substitution - Missense) https://cancer.sanger.ac.uk/cosmic/mutation/overview?id=99455550
- ↑ Wall TL, Thomasson HR, Schuckit MA, Ehlers CL. Subjective feelings of alcohol intoxication in Asians with genetic variations of ALDH2 alleles. Alcohol Clin Exp Res. 1992 Oct;16(5):991-5. doi:, 10.1111/j.1530-0277.1992.tb01907.x. PMID:1443441 doi:http://dx.doi.org/10.1111/j.1530-0277.1992.tb01907.x
- ↑ 10.0 10.1 10.2 10.3 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
- ↑ Guillot A, Ren T, Jourdan T, Pawlosky RJ, Han E, Kim SJ, Zhang L, Koob GF, Gao B. Targeting liver aldehyde dehydrogenase-2 prevents heavy but not moderate alcohol drinking. Proc Natl Acad Sci U S A. 2019 Dec 17;116(51):25974-25981. doi:, 10.1073/pnas.1908137116. Epub 2019 Dec 2. PMID:31792171 doi:http://dx.doi.org/10.1073/pnas.1908137116
