1. The disease beriberi, which results from a dietary deficiency of vitamin B1 (Thiamine) is characterized by neurological and cardiac symptoms, as well as increased levels of pyruvate and alpha- ketoglutarate in the blood. How does a deficiency of thiamine account for the increased levels of pyruvate and alpha- ketoglutarate?
2. Patients in shock experience decreased delivery of oxygen to tissues, decreased activity of the pyruvate dehydrogenase complex, and increased anaerobic metabolism. Excess pyruvate is converted to lactate, which accumulates in tissues and in the blood, causing lactic acidosis.
a. Since oxygen is not a reactant or a product in the citric acid cycle, why do low levels of oxygen decrease the activity of the pyruvate dehydrogenase complex?
b. To alleviate lactic acidosis, shock patients are sometimes given dichloroacetate, which inhibits pyruvate dehydrogenase kinase. How does this treatment affect the activity of the pyruvate dehydrogenase complex?
3. The reaction for which the enzyme pyruvate kinase is named never occurs in the cell. Briefly discuss this.