Question

typical exam questions

1. why does a low km enzyme work better in vivo?
2. what happens if alddhmt is defective?
3. why do some people flush after alcohol?
4. which enzyme produces acetaldehyde?
5. which enzyme detoxifies acetaldehyde?
6. why is alddhcyto insufficient?
7. how does disulfiram work?
8. what is the toxic intermediate?
9. what is the role of nad⁺?
10. how does this relate to enzyme kinetics?

Explanation:

1. Low $K_m$ means high substrate affinity, so enzymes function well at the low substrate concentrations present in living organisms.
2. Mitochondrial aldehyde dehydrogenase (AldDHmt) deficiency leads to impaired acetaldehyde breakdown, causing buildup of this toxic metabolite.
3. Alcohol flush occurs when AldDHmt is defective: acetaldehyde accumulates, triggering vasodilation of facial blood vessels.
4. Alcohol dehydrogenase (ADH) catalyzes the conversion of ethanol to acetaldehyde.
5. Mitochondrial aldehyde dehydrogenase (AldDHmt) is the primary enzyme that detoxifies acetaldehyde by converting it to acetate.
6. Cytosolic aldehyde dehydrogenase (AldDHcyto) has low affinity for acetaldehyde (high $K_m$) and low activity, so it cannot effectively clear acetaldehyde when levels rise.
7. Disulfiram inhibits AldDHmt, preventing acetaldehyde breakdown. This leads to toxic buildup, causing unpleasant symptoms that deter alcohol consumption.
8. Acetaldehyde is the toxic intermediate produced during alcohol metabolism.
9. $NAD^+$ acts as a coenzyme (electron acceptor) for ADH and AldDH, accepting hydrogen atoms during the oxidation of ethanol and acetaldehyde.
10. Alcohol metabolism enzymes follow Michaelis-Menten kinetics: $K_m$ values determine their affinity for substrates, and defects in enzymes (like low-Activity AldDHmt) alter reaction rates and metabolite buildup, which aligns with enzyme kinetic principles of substrate affinity and catalytic efficiency.

Answer:

1. It has high substrate affinity, works at low [substrate].
2. Acetaldehyde accumulates, causing toxic effects.
3. Defective AldDHmt causes acetaldehyde buildup, vasodilation.
4. Alcohol dehydrogenase (ADH)
5. Mitochondrial aldehyde dehydrogenase (AldDHmt)
6. Low acetaldehyde affinity, low catalytic activity.
7. Inhibits AldDHmt, blocks acetaldehyde breakdown.
8. Acetaldehyde
9. Electron acceptor coenzyme for metabolic enzymes.
10. Enzyme $K_m$ and activity determine metabolite clearance, matching Michaelis-Menten kinetics.