The pyruvate dehydrogenase complex catalyzes the reaction py

The pyruvate dehydrogenase complex catalyzes the reaction pyruvate-->acetyl-Coa. Individuals who express defective form of pyruvate dehydrogenase complex constantly feel tired. What is the basis for this?

Solution

Pyruvate dehydrogenase complex deficiency is a common neurogenerative disorder due to a mutation on E1 subunit of the X-linked alpha gene. it disrupts the conversion of pyruvate t acetyl co A which is a major step in the citric acid cycle, one of the important pathways for energy from carbohydrate metabolism. defects in this enzyme build up lactate levels leading to lactic acidosis with non-specific symptoms such as illness, tired, lethargy, tachypnea and poor feeding. Neurological symptoms are observed during infancy leading to delayed neurological developments, ataxia, microcephaly and mental retardation which is termed as leighs syndrome.

Lactic acidosis shows increased production of lactate from pyruvate by lactate dehydrogenase. These lactate increase in tissues rapidly along with protons than the rate by which they are removed. So, there is an impairment in the functioning of cells and tissues. Mitochondrial defects are observed leading to insufficient ATP synthesis.