What is the consequence of a pyruvate carboxylase deficiency in terms of lactic acidemia?

A deficiency in pyruvate carboxylase leads to lactic acidemia because it prevents the conversion of pyruvate to oxaloacetate. This results in pyruvate accumulation, which is then converted to lactic acid, causing an increase in lactate levels in the blood.

When pyruvate carboxylase is deficient, pyruvate cannot be converted to oxaloacetate, which is necessary for replenishing TCA cycle intermediates. The decrease in oxaloacetate prevents acetyl-CoA from being converted to citrate, leading to an accumulation of acetyl-CoA in the mitochondria. This elevated acetyl-CoA inhibits pyruvate dehydrogenase, causing further pyruvate accumulation in the cytoplasm. The excess pyruvate is then converted to lactic acid, resulting in lactic acidemia.