[20 pts] Alcohol Flushing Syndrome Humans with the alcohol flushing syndrome (AFS) tend to flush red...

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[20 pts] Alcohol Flushing Syndrome Humans with the "alcohol flushing syndrome" (AFS) tend to flush red after consuming ethanol. When an individual with AFS consumes alcohol, acetaldehyde accumulates in their blood. Acetaldehyde causes blood vessels to dilate, causing the skin to flush red. Genetically, individuals with AFS carry an inherited mutation in the gene encoding the mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2). This mutation severely compromises the catalytic properties of ALDH2, which ultimately causes the acetaldehyde accumulation. 1.1. [4 pts] The human pathway for metabolizing alcohol starts with the enzyme alcohol dehydrogenase, which catalyzes the conversion of ethanol (C2H5OH) to acetaldehyde (CH3CHO). This is followed by aldehyde dehydrogenase 2 (ALDH2, the enzyme of interest in this problem), which catalyzes the conversion of acetaldehyde and HS-CoA to acetyl-CoA (CH3CO-S-COA). The TCA cycle then takes over and oxidizes the acetyl-CoA to CO2. Draw two diagrams of this pathway-one for an individual without AFS and another for an individual with AFS. On the basis of your diagrams, explain how ALDH2 deficiency combined with ethanol input into the bloodstream could culminate in the accumulation of acetaldehyde in the blood. This subquestion is based on material covered in lecture L410. 1.2. [3 pts] Determine whether NADH or NAD* is consumed in the two chemical reactions from ethanol to acetyl-CoA described in 1.1. Note that if NADH is consumed, NAD+ is regenerated and vice versa. Show your work. This part of the problem is based on material covered in lecture L410. This subquestion is based on material covered in lecture L410. 1.3. [3 pts] Individuals without AFS have a glutamic acid at position 487 on the ALDH2 protein, whereas individuals with AFS have a lysine at this position. Using what you determined in 1.2, provide a plausible chemical explanation justifying why the properties of the enzyme could be so drastically altered by this single amino acid substitution. Keep in mind that the enzyme has two substrates, one of which is acetaldehyde and the other is NADH or NAD* (as you determined in 1.2). This subquestion is based on material covered in lecture L210. [20 pts] Alcohol Flushing Syndrome Humans with the "alcohol flushing syndrome" (AFS) tend to flush red after consuming ethanol. When an individual with AFS consumes alcohol, acetaldehyde accumulates in their blood. Acetaldehyde causes blood vessels to dilate, causing the skin to flush red. Genetically, individuals with AFS carry an inherited mutation in the gene encoding the mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2). This mutation severely compromises the catalytic properties of ALDH2, which ultimately causes the acetaldehyde accumulation. 1.1. [4 pts] The human pathway for metabolizing alcohol starts with the enzyme alcohol dehydrogenase, which catalyzes the conversion of ethanol (C2H5OH) to acetaldehyde (CH3CHO). This is followed by aldehyde dehydrogenase 2 (ALDH2, the enzyme of interest in this problem), which catalyzes the conversion of acetaldehyde and HS-CoA to acetyl-CoA (CH3CO-S-COA). The TCA cycle then takes over and oxidizes the acetyl-CoA to CO2. Draw two diagrams of this pathway-one for an individual without AFS and another for an individual with AFS. On the basis of your diagrams, explain how ALDH2 deficiency combined with ethanol input into the bloodstream could culminate in the accumulation of acetaldehyde in the blood. This subquestion is based on material covered in lecture L410. 1.2. [3 pts] Determine whether NADH or NAD* is consumed in the two chemical reactions from ethanol to acetyl-CoA described in 1.1. Note that if NADH is consumed, NAD+ is regenerated and vice versa. Show your work. This part of the problem is based on material covered in lecture L410. This subquestion is based on material covered in lecture L410. 1.3. [3 pts] Individuals without AFS have a glutamic acid at position 487 on the ALDH2 protein, whereas individuals with AFS have a lysine at this position. Using what you determined in 1.2, provide a plausible chemical explanation justifying why the properties of the enzyme could be so drastically altered by this single amino acid substitution. Keep in mind that the enzyme has two substrates, one of which is acetaldehyde and the other is NADH or NAD* (as you determined in 1.2). This subquestion is based on material covered in lecture L210.

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11 Step 1 C2H6Oethanol NAD C2H4Oacetaldehyde NADH H this reaction is catalyzed by alcohol dehydrogen... View the full answer