An inherited neurologic disorder, characterized by spinocerebellar degeneration,
ID: 254141 • Letter: A
Question
An inherited neurologic disorder, characterized by spinocerebellar degeneration, is associated with low activity of pyruvate dehydrogenase and ?-ketoglutarate dehydrogenase. (It is not clear whether this is directly or only indirectly involved in the pathogenesis of this disease.)
i. What protein do pyruvate dehydrogenase and ?-ketoglutarate dehydrogenase have in common that might be therefore simultaneously affected by a single inherited defect? ii. What would be the effect of this deficiency on glycolysis (increased, decreased, the same), lactate fermentation and the cellular concentration of ATP (increased, decreased, the same)? Explain.
b) After only four minutes without oxygen, a person starts to suffer from brain damage. Explain in terms of the effect of the lack of oxygen on oxidative phosphorylation, the electron transport system, and the tricarboxylic acid cycle. What molecule is deficient? How/why do these effects lead to brain damage?
Explanation / Answer
i) Pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase have in common E1 alpha subunit, a complex of pyruvate dehydrogenase, that might be affected by a single inherited defect. This protein leads to pyruvate dehydrogenase deficiency, which is a congenital degenerative metabolic disease resulting from a mutation of the pyruvate dehydrogenase complex located on X chromosome.
ii) In glycolysis, one molecule of glucose is converted into two pyruvate molecule, which requires 2 ATP molecule, which is useless if pyruvate dehydrogenase complex.
Similarly, lactate fermentation is also affected by the deficiency of this enzyme.
Malfunctioning of citric acid cycle due to its deficiency deprives the body of energy and leads to abnormal buildup of lactate.