Exploring How the ALDH2*2 Mutation Affects Aldehyde Metabolism During Malaria Infection
Additional Funding Sources
The project described was supported by the Research Experience for Undergraduates Program Site: Molecular and organismal evolution at the University of Idaho under Award No. 1757826. The project was also supported by the University of Idaho through the College of Agricultural and Life Sciences and the University of Idaho Summer Research Experiences for Undergraduates Program.
Presentation Date
7-2019
Abstract
Aldehyde dehydrogenases (ALDH) are an important group of enzymes involved in the ethanol detoxification process. Aldehyde dehydrogenase 2 (ALDH2) is abundant in the liver where it catalyzes the conversion of acetaldehyde to acetic acid. The ALDH2*2 mutation replaces a glutamate with a lysine at position 487 which is in the active site, thereby inhibiting enzyme activity and resulting in an accumulation of harmful aldehydes. This mutation occurs naturally in 600 million people of Asian descent and is associated with ‘Asian flushing syndrome’. The genomes of malaria parasites in the genus Plasmodium do not encode proteins in the ALDH family of proteins, suggesting that malaria parasites rely on the host to detoxify aldehydes. Here we evaluated the effect of the ALDH2*2 mutation on aldehyde metabolism in mice with malaria. Wild type mice and mice with the ALDH2*2 mutation were monitored during infection with Plasmodium yoelii for blood aldehyde levels, ALDH enzyme activity as well as markers of liver damage. Hypotheses regarding host-parasite interactions and selection pressures for the development of host defenses as well as the potential to use this biology to develop novel therapeutic strategies for malaria are presented.
Exploring How the ALDH2*2 Mutation Affects Aldehyde Metabolism During Malaria Infection
Aldehyde dehydrogenases (ALDH) are an important group of enzymes involved in the ethanol detoxification process. Aldehyde dehydrogenase 2 (ALDH2) is abundant in the liver where it catalyzes the conversion of acetaldehyde to acetic acid. The ALDH2*2 mutation replaces a glutamate with a lysine at position 487 which is in the active site, thereby inhibiting enzyme activity and resulting in an accumulation of harmful aldehydes. This mutation occurs naturally in 600 million people of Asian descent and is associated with ‘Asian flushing syndrome’. The genomes of malaria parasites in the genus Plasmodium do not encode proteins in the ALDH family of proteins, suggesting that malaria parasites rely on the host to detoxify aldehydes. Here we evaluated the effect of the ALDH2*2 mutation on aldehyde metabolism in mice with malaria. Wild type mice and mice with the ALDH2*2 mutation were monitored during infection with Plasmodium yoelii for blood aldehyde levels, ALDH enzyme activity as well as markers of liver damage. Hypotheses regarding host-parasite interactions and selection pressures for the development of host defenses as well as the potential to use this biology to develop novel therapeutic strategies for malaria are presented.
Comments
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