TCA Cycle

A 52-year-old man with a history of chronic alcohol abuse presents with confusion, ataxia, and ophthalmoplegia. Biochemical analysis reveals severely reduced activity of α-ketoglutarate dehydrogenase complex. Which of the following is the most common cofactor deficiency responsible for this enzyme dysfunction?

All of the following TCA cycle intermediates can be replenished by anaplerotic reactions EXCEPT:

A 42-year-old woman with a 10-year history of mitochondrial cytopathy presents with progressive muscle weakness, fatigue, and recurrent episodes of lactic acidosis triggered by infection or exercise. Her serum lactate is persistently elevated (6–8 mmol/L) despite supportive care. She has been trialed on multiple cofactors without sustained benefit. Which drug is the most appropriate choice to reduce lactate accumulation by enhancing pyruvate oxidation through the TCA cycle?

A 28-year-old woman from Delhi with a 6-month history of progressive fatigue, dyspnea on exertion, and recurrent infections is found to have a serum lactate of 6 mmol/L (normal <2) and pyruvate of 0.3 mmol/L (normal <0.1) at rest. Muscle biopsy shows ragged-red fibers and electron microscopy reveals abnormal mitochondrial morphology. Genetic sequencing confirms a heteroplasmic mutation in the mitochondrial DNA-encoded NADH dehydrogenase (Complex I) gene. She is currently on standard supportive care. What is the most appropriate immediate next step in management?

Which enzyme-catalyzed step best distinguishes the oxidative decarboxylation of pyruvate (entry into TCA cycle) from the oxidative decarboxylation of isocitrate (within TCA cycle)?