Question

9.) (4 pts) A thiamine deficiency causes the disease beriberi. The symptoms are pain in the limbs, weakness of the muscles and distorted skin sensations. The heart becomes enlarged and the cardiac output diminishes. (a) Which of the metabolic pathways that we have studied would be affected by a thiamine deficiency? List the affected enzymes. Pyruvate dehydrogenasc (b) A deficiency of thiamine elevates the blood levels of pyruvate and a-ketoglutarate. How are these effects related to the deficiency? boldog

Answer 1

Answer (a)

Affected enzymes:

Pyruvate dehydrogenase

α-ketogluterate dehydrogenase

Transketolase

Pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase require thiamine as a cofactor in the Kreb’s cycle.

Transketolase is an important enzyme in the Pentose phosphate pathway (PPP) that requires thiamine as a cofactor.

Answer (b)

Thiamine is the precursor of the cofactor thiamine pyrophosphate (TPP). Thiamine pyrophosphate ( active form of thiamine) is a prosthetic group of three enzymes: Pyruvate dehydrogenase, α-ketogluterate dehydrogenase, Transketolase.

Deficiency of thiamine causes pyruvate and α-ketogluterate to accumulate in blood because they cannot be metabolized by these enzymes.

Thiamine (precursor) -------------> TPP ( Cofactor for) --------------> Pyruvate dehydrogenase, α-ketogluterate dehydrogenase, Transketolase ( Metabolizes)------------> pyruvate and α-ketogluterate

Thiamine deficiency ----------------> No TPP ----------------> No Pyruvate dehydrogenase, α-ketogluterate dehydrogenase, Transketolase -------------> No metabolism of pyruvate and α-ketogluterate ------------> Increased level of pyruvate and α-ketogluterate in blood.