Hi, I need some assistance with the following questions:
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?
1. Thiamine is needed as an essential co-factor for the pyruvate dehydrogenase complex. The catalytic activity of the complex actually consists of three enzymes: pyruvate dehydrogenase, dihydrolipoamide acyltransferase and dihydrolipoamide dehydrogenase. Five non-protein co-factors are required for the enzymes to be catalytically active. They are: NAD+, CoA, TPP, lipoic acid and FAD.
TPP stands for thiamine pyrophosphate. Without this co-factor, the enzyme is inactive. Thiamine pyrophosphate is made from thiamine (B1). Therefore, with insufficient thiamine, the pyruvate dehydrogenase complex will not function well, and as a result, pyruvate will accumulate.
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