TCA Cycle

A 28-year-old woman from Delhi presents with progressive fatigue, muscle weakness, and recurrent episodes of lactic acidosis since childhood. Her mother had similar symptoms. Serum lactate is elevated at 8 mmol/L (normal <2). Pyruvate is 2.5 mmol/L (normal 0.3–0.9). MRI brain shows basal ganglia hyperintensities. Genetic testing reveals mutations in the PDHA1 gene encoding pyruvate dehydrogenase complex subunit E1α. Which of the following TCA cycle intermediates would be MOST depleted in this patient?

Which enzyme catalyzes the conversion of succinyl-CoA to succinate in the TCA cycle, and what is its cofactor requirement?

Which intermediate of the TCA cycle is regenerated at the end of each cycle, and how many carbon atoms does it contain?

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?