You are the physician examining a 6-year-old boy who has been experiencing progressive muscle weakness. You perform assays on muscle biopsy tissue from this patient and find that mitochondrial oxidation of succinate is normal but that pyruvate
Oxidation is severely impaired. Mitochondrial extracts demonstrate that the activity of the pyruvate dehydrogenase complex (PDHc) is normal as is the activity of malate dehydrogenase. These results are consistent with the patient harboring a defect in which of the following mitochondrial components?

Question

Quizplus · Accepted Answer

The normal oxidation of succinate indicates that complex II is functioning properly. However, the impaired oxidation of pyruvate suggests a defect in complex I, which is involved in the initial step of the electron transport chain where electrons from NADH (produced from pyruvate oxidation) are transferred.  Since the PDHc activity of the patient's mitochondria was shown to be normal but the NADH produced by this reaction could not be reoxidized via electron transport, it suggests that the defect causing the muscle weakness is in mitochondrial complex I. Succinate oxidation was normal indicating that electron flow to complex II is not impaired, further strengthening the argument that the defect lies in complex I. If ATP synthase were defective neither pyruvate nor succinate oxidation would be normal.

You Are the Physician Examining a 6-Year-Old Boy Who Has