The Development of Gluconeogenic Function in Rat Liver

Abstract

Earlier work has shown that the incorporation of pyruvate into glucose and glycogen occurs at negligible rates in slices from fetal rat liver and that this overall pathway appears at birth. Measurement of gluconeogenic enzymes during the transition from the fetus to the newborn suggested that the absence of cytosol P-enolpyruvate carboxykinase limits gluconeogenesis in the fetus. Although a mitochondrial activity of P-enolpyruvate carboxykinase is active in fetal rat liver, it seemed unlikely that this enzyme was participating in gluconeogenesis. This was particularly obvious in fetal guinea pig liver which, like the fetal rat liver, does not have a functional gluconeogenic pathway, but contains a very active mitochondrial P-enolpyruvate carboxykinase. Purification of P-enolpyruvate carboxykinase from the cytosol fraction of rat liver permitted the conclusive demonstration that the cytosol and mitochondrial enzymes were distinct, but did not explain why fetal liver slices could not carry out gluconeogenesis.