in class practice questions

Zellweger syndrome is rare genetic condition caused by a mutation in the Pex5 gene. Infants

born with this mutation die less than 1 year after birth because the peroxisome is unable to

breakdown lipids, and they accumulate to lethally high levels. Predict the reason for the

complications caused by this disease.

1. Peroxisome proteins are unable to unbind from the ribosome.

2. The peroxisome membrane is unable to form large enough channels.

3. Peroxisome proteins are unable to enter the organelle.

4. Peroxisome proteins are unable to fold properly in the ER.

Peroxisome proteins are unable to enter the organelle.

explain the answer to this question: Zellweger syndrome is rare genetic condition caused by a mutation in the Pex5 gene. Infants born with this mutation die less than 1 year after birth because the peroxisome is unable to breakdown lipids, and they accumulate to lethally high levels. Predict the reason for the -\complications caused by this disease.

The PEX5 gene encodes the peroxisomal targeting signal 1 (PTS1) receptor. This receptor protein is responsible for recognizing newly synthesized peroxisomal matrix proteins (like the enzymes that break down lipids) in the cytosol and shuttling/importing them across the membrane into the peroxisome.

If the PEX5 gene is mutated:

The import machinery fails, so peroxisomal enzymes remain stranded in the cytosol instead of entering the organelle.

Without its functional lipid-degrading enzymes inside, the peroxisome cannot breakdown long-chain fatty acids (lipids), leading to their toxic accumulation and the severe symptoms of Zellweger syndrome

88% of cases of Pyruvate Dehydrogenase Complex Deficiency (PDCD) are caused by a mutation in the MTS of the pyruvate dehydrogenase-alpha polypeptide. Use the graphic below to decide which method would be most effective in treating this condition.

1. A thiamine rich diet to compensate for the low binding by pyruvate dehydrogenase.

2. A ketogenic diet to reduce the amount of pyruvate produced.

3. A plasma transfusion enriched with chaperone proteins.

4. Gene therapy for a Timm to better bind to the MTS

A ketogenic diet to reduce the amount of pyruvate produced.

explain the answer to this question: 88% of cases of Pyruvate Dehydrogenase Complex Deficiency (PDCD) are caused by a mutation in the MTS of the pyruvate dehydrogenase-alpha polypeptide. Use the graphic below to decide which method would be most effective in treating this condition.

The Problem: The prompt notes that the mutation occurs in the MTS (Mitochondrial Targeting Signal) of the pyruvate dehydrogenase subunit. This means pyruvate dehydrogenase fails to import properly into the mitochondria. As shown in your diagram, when pyruvate dehydrogenase is non-functional, pyruvate cannot be converted into Acetyl-CoA and gets diverted into Lactate via lactate dehydrogenase, causing dangerous lactic acid buildup while starving the Krebs Cycle of fuel.

Why a Ketogenic Diet Works: A ketogenic diet is high in fats and low in carbohydrates. Fatty acid breakdown bypasses pyruvate dehydrogenase entirely, generating Acetyl-CoA directly to fuel the Krebs Cycle. It also minimizes carbohydrate intake, drastically reducing pyruvate generation and preventing severe lactic acidosis.

How would you know if a polypeptide has been extruded (that is, pushed or forced) into a membrane-bound organelle

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