The redistribution of carbon label by the reactions involved in glycolysis, gluconeogenesis and the tricarboxylic acid cycle in rat liver

A scheme is presented that shows how the reactions involved in gluconeogenesis, glycolysis and the tricarboxylic acid cycle are linked in rat liver. Equations are developed that show how label is redistributed in aspartate, glutamate and phosphopyruvate when it is introduced as specifically labelled pyruvate or glucose either at a constant rate (steady-state theory) or at a variable rate (non-steady-state theory). For steady-state theory the fractions of label introduced as specifically labelled pyruvate that are incorporated into glucose and carbon dioxide are also given, and for both theories the specific radioactivities of aspartate and glutamate relative to the specific radioactivity of the substrate. The theories allow for entry of label into the tricarboxylic acid cycle via both oxaloacetate and acetyl-CoA, for (14)CO(2) fixation and for loss of label from the tricarboxylic acid cycle in glutamate, but not for losses in citrate. They also allow for incomplete symmetrization of label in oxaloacetate due to incomplete equilibration with fumarate both in the extramitochondrial part of the cell and in the mitochondrion on entry of oxaloacetate into the tricarboxylic acid cycle. In the latter case failure both of oxaloacetate to equilibrate with malate and of malate to equilibrate with fumarate are considered.