The citrate is either exported to the cytosol for lipid biosynthesis or it may be metabolised by the other Krebs cycle enzymes. Very rapid fat oxidation may generate copious supplies of NADH and acetyl CoA which can overload the above system, with the result that almost all the oxaloacetate is reduced to malate and diverted into gluconeogensis. This effect is important during prolonged fasting and in uncontrolled diabetes. It may lead to the pathological condition of ketoacidosis. However, acetoacetate and hydroxybutyrate are common metabolites in healthy people and important fuels for the heart and brain.
Pyruvate kinase is required for glycolysis.
This makes it very difficult to reverse the pyruvate kinase reaction in one step during gluconeogenesis. This coordinates metabolism at the start and finish of the glycolytic pathway and ensures that liver cells do not attempt both glycolysis and gluconeogenesis at the same time. Acetyl-CoA carboxylase is expressed mainly in liver and adipose tissue where it generates the malonyl CoA that is required for lipogenesis. It requires biotin as a cofactor and closely resembles pyruvate carboxylase and propionyl CoA carboxylase. OMIM entry for liver.