Figure 1. Schematic representation of the pathway of gluconeogenesis. The reactions catalysed by four key enzymes of gluconeogenesis – pyruvate carboxylase (PC), cytoplasmic phosphoenolpyruvate carboxykinase (PEPCK-C) or mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M), fructose-1,6-bisphosphatase (F1,6BPase) and glucose-6-phosphatase (G6Pase) (circled) – are indicated by red arrows; the opposing reactions of glycolysis catalysed by pyruvate kinase (PK), 6-phosphofructo-1-kinase (6PF1K) and glucokinase (GK) (circled) are shown by blue arrows. The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6PKF2K/F2,6BPase) is indicated by a ‘B’ (circled). The allosteric inhibition of F1,6BPase by fructose 2,6-bisphosphate (F-2,6-BP) and PK by alanine are shown by dashed green arrows with a negative sign. The allosteric activation of 6PF1K by F-2,6-BP, of PK by F-1,6-BP and of PC by acetylcoenzyme A (AcCoA) is indicated by dashed green arrows with a positive sign. In the interests of clarity and simplicity, other reactions and membrane transporters are shown by thin black arrows. Only the main substrates, alanine (Ala) and pyruvate (Pyr), as well as the key intermediates phosphoenolpyruvate (PEP), fructose 1,6-bisphosphate (F-1,6-BP), fructose 6-phosphate (F-6-P) and glucose 6-phosphate (G-6-P) are shown. The plasma membrane, endoplasmic reticulum and mitochondrial membrane are shown schematically by thin parallel lines.

Figure 2. The Cori (glucose–lactate) (red arrows) and the glucose–alanine (blue arrows) cycles. In the glucose–lactate cycle, pyruvate formed in skeletal muscle (and in a number of other tissues) is reduced to lactate, which is released into the blood, taken up by the liver, used to form glucose, which is then released to the blood and taken up by skeletal muscle and other peripheral tissues. Alanine is formed from pyruvate and glutamate in skeletal muscle and undergoes a similar cycling.