BeriBeri is a neurological and cardiovascular disease that is the result of thia

Question

BeriBeri is a neurological and cardiovascular disease that is the result of thiamine deficiency. The disease can result in lactic acidosis and elevated alpha-ketoglutarate levels in the blood. Interestingly both mercury and arsenite poisoning can lead to symptoms and blood work that mirror BeriBeri. Both mercury and arsenite have high reactivity for free sulfhydryls and form covalent bonds with them. Given this information explain how a thiamine deficiency or mercury/arsenite poisoning lead to lactic acidosis. A full answer will describe the mechanism of their (thiamine deficiency and mercury/arsenite poisoning) action.

Explanation / Answer

The disturbance of pyruvate metabolism is the cause of lactic acidosis and elevated alpha-keto-glutarate levels in the blood. Thiamine is a vitamin that play an important role in carbohydrate metabolism. In the condition of thiamine deficiency, pyruvate metabolism is affected that led the accumulation of pyruvate that finally metabolized to lactate and result in lactic acidosis.

In arsenic poisoning, the pyruvate dehydrogenase complex inhibition by allosteric modulation in pyruvate metabolism. This enzyme, complex catalyzes the reaction Pyruvate + CoA-SH + NAD+ PDH Acetyl-Co-A + NADH + CO2 . Inhibition of pyruvate metabolism, lead to the accumulation of pyruvate that finally metabolized to lactate and result in lactic acidosis. High level of lactic acid in the body that result in excessive low pH in blood.

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