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Patients in shock experience reduced delivery of oxygen to tissues, reduced activity of the pyruvate dehydrogenase complex, and raised anaerobic metabolism. Excess pyruvate is transformed to lactate, that accumulates in tissues and in the blood, causing the lactic acidosis.
a) Since oxygen is not a reactant or a product in the citric acid cycle, explain why do low levels of oxygen reduce the activity of the pyruvate dehydrogenase complex?
b) To alleviate the lactic acidosis, shock patients are sometimes given dichloroacetate that inhibits pyruvate dehydrogenase kinase. Explain how does this treatment influence the activity of the pyruvate dehydrogenase complex?