ALDH2: Difference between revisions

Line 87:

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~~ ==

== Inhibitors and activators ==

ALDH2 can be selectively inhibited by Daidzin, as ALDH1 by Antabuse (disulfiram, DS, tetraethylthiuram disulfide), an early alcoholic treatment, as it causes accumulation of acetaldehyde resulting in heavier hangover symptoms. Daidzin is more specific to ALDH2 than to ALDH1, this could be due to a smaller substrate-binding cleft than of ALDH1. The daidzin binding sites are spread over all four subunits. The fully bound daidzin is buried from 90%. The isoflavon ring structure conducts extensive Van der Waals contacts with the surrounding residues, including long contact with Cys302. Cys302 was identified as an important catalyst group. The separation of Daidzin O4′-hydroxyl oxygen from Cys302 sulfur atoms is 3.7 Å, and there is no covalent interaction. Despite the general similarity of the ALDH2 apo and daidzin structures, the conformation has been locally altered. The lateral chain of Cys302 moves 2.5 Å from the site to avoid close contact with the O4′-phenoxy ring of Daidzin. Other isoflavonoid derivatives show some inhibitory impact on ALDH2, although prunetin does not result in structural changes as it binds only one subunit per tetramer. Studies of structural activity indicate that the 7-O position can be replaced by several straight chain alkyls with terminal polar functions such as -OH, -COOH, or -NH<sub>2</sub>. It was observed that longer ethyl group has better hydrophobic interactions resulting in better binding, longer chains can result in lesser affinity due to more complex formation of both polar and nonpolar interactions at the same time<ref>DOI: 10.1021/jm800488j</ref>.

== References ==

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@@ Line 87: / Line 87: @@
 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 ==
+== Inhibitors and activators ==
+ALDH2 can be selectively inhibited by Daidzin, as ALDH1 by Antabuse (disulfiram, DS, tetraethylthiuram disulfide), an early alcoholic treatment, as it causes accumulation of acetaldehyde resulting in heavier hangover symptoms. Daidzin is more specific to ALDH2 than to ALDH1, this could be due to a smaller substrate-binding cleft than of ALDH1. The daidzin binding sites are spread over all four subunits. The fully bound daidzin is buried from 90%. The isoflavon ring structure conducts extensive Van der Waals contacts with the surrounding residues, including long contact with Cys302. Cys302 was identified as an important catalyst group. The separation of Daidzin O4′-hydroxyl oxygen from Cys302 sulfur atoms is 3.7 Å, and there is no covalent interaction. Despite the general similarity of the ALDH2 apo and daidzin structures, the conformation has been locally altered. The lateral chain of Cys302 moves 2.5 Å from the site to avoid close contact with the O4′-phenoxy ring of Daidzin. Other isoflavonoid derivatives show some inhibitory impact on ALDH2, although prunetin does not result in structural changes as it binds only one subunit per tetramer. Studies of structural activity indicate that the 7-O position can be replaced by several straight chain alkyls with terminal polar functions such as -OH, -COOH, or -NH<sub>2</sub>. It was observed that longer ethyl group has better hydrophobic interactions resulting in better binding, longer chains can result in lesser affinity due to more complex formation of both polar and nonpolar interactions at the same time<ref>DOI: 10.1021/jm800488j</ref>.
 == References ==
 <references/>