A 26 years old patient initially presented with a history of fatigability dating back to early childhood. Even very mild exercise resulted in a rapid exhaustion. After 4 minutes on a bicycle ergometer, the patient’s blood lactate concentration rose from 0.8mM to 10mM;it dropped slowly after the end of the exercise but was still elevated 90 minutes later.
A muscle biopsy was obtained and mitochondria isolated from it. The rates of oxygen utilization by these mitochondria with various substrate in the presence of ADP, together with compatible values for mitochondria from a normal volunteer, are shown below.
Oxygen consumption (nanoatoms/min/mg protein)
Substrate Patient Control
Pyruvate 17 92
Glutamate 17 68
Succinate 50 55
(a) Describe the observed differences between the patient’s and control mitochondria.
(b) From the data presented, suggested a possible site for the defect in the patient’s muscles. Suggest two other substrates which might be tested to substantiate your conclusion, and the expected results with these substrates.
(c) Describe the mechanism which would lead to excessive lactate production when the patient exercised.
(d) Why did the patient become fatigued so rapidly?
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