We often think of gluconeogenesis as starting with pyruvate, but other carbon sources than pyruvate can be used to make glucose via gluconeogenesis. Some of these molecules and their points of entry into gluconeogenesis are shown in Figure 16.4.

Note that breakdown products of fat metabolism (glycerol, propionyl-CoA), protein degradation (alanine, other amino acids), and anaerobic glycolysis (lactate) are substrates for gluconeogenesis. Notably, the primary breakdown product of fat, acetyl-CoA , is not shown, because it cannot be effectively used by animals in gluconeogenesis. Some of the substrates are summarized as follows:

Lactate - the most significant gluconeogenesis precursor. Lactate is produced when insufficient oxygen is present to maintain aerobic glycolysis. Lactate in exercising muscle is released into the blood where it travels to the liver for participation in gluconeogenesis. The newly synthesized glucose reenters the blood and travels back to the muscle where it is needed. This cycle, called the Cori cycle, is shown in Figure 16.5.

Amino Acids - Alanine and 17 other amino acids from proteins yield gluconeogenic precursors in their catabolic pathways. Only leucine and lysine do not produce gluconeogenic precursors. Amino acids which produce gluconeogenic precursors are called glucogenic. During starvation or fasting, catabolism of muscle proteins occurs as a means of generating sufficient precursors for gluconeogenesis that are not available in the diet.

Glycerol - the backbone of the fats and glycerophospholipids. Aside from propionyl-CoA produced by oxidation of rare, odd-chain fatty acids, glycerol is the only portion of the fat molecule that can be made into glucose by animals.

Propionate - Oxidation of fatty acids containing an odd number of carbons ultimately yields a three carbon molecule, propionyl-CoA. Propionyl-CoA is converted to succinyl-CoA in an unusual set of reactions shown here. Succinyl-CoA can ultimately be converted to the gluconeogenic intermediate, oxaloacetate.