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Breaking down the structure of the enzyme ALDH2: 1 tequila, 2 tequila…..ASIAN FLUSH!

Breaking down the structure of the enzyme ALDH2: 1 tequila, 2 tequila…..ASIAN FLUSH!. Human Mitochondrial Aldehyde Dehydrogenase (ALDH2). ALDH2 catalyzes the conversion of acetaldehyde, an intermediate product of ethanol, into acetic acid. *. *. ASIAN FLUSH Demographics.

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Breaking down the structure of the enzyme ALDH2: 1 tequila, 2 tequila…..ASIAN FLUSH!

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  1. Breaking down the structure of the enzyme ALDH2: 1 tequila, 2 tequila…..ASIAN FLUSH!

  2. Human Mitochondrial Aldehyde Dehydrogenase (ALDH2) • ALDH2 catalyzes the conversion of acetaldehyde, an intermediate product of ethanol, into acetic acid. * *

  3. ASIAN FLUSH Demographics • Approximately 40% of East Asians have a reduced ALDH2 function, due to the mutation of Glu to Lys at amino acid 487. • Results in high levels of acetaldehyde in the blood • Symptoms include facial flushing, light headedness, palpitations, nausea, and general “hangover” symptoms occur .

  4. Genetics • Homozygotes of the Glu487Lys mutation have zero ALDH2 activity • Heterozygotes of same mutation have reduced ALDH2 activity • The mutation is a partial dominant • Drugs to treat alcohol abusers mimic the Asian Flush phenotype

  5. ALDH2 dimer with key connections at E487 E487 NAD+

  6. NAD+ Binding Site Glu487Lys Superimposed wild type and Flushing isoform ALDH2 (A chain only)

  7. Conclusions • Homozygotes of the Glu487Lys mutation have zero ALDH2 activity • Heterozygotes of same mutation have reduced ALDH2 activity • Active site sequence is evolutionarily conserved • The position of the mutation (E487K) could disrupt interactions between protein monomers • The mutation causes structural changes within the protein that could disrupt interactions with NAD+ as well.

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