Definition: Gluconeogenesis is the process of de novo synthesis of glucose from non-sugar precursors. Gluconeogenesis does not include the conversion of galactose or fructose into glucose or the generation of glucose from glycogen via glycogenolysis. Process: The pathway of gluconeogenesis mainly occurs in the kidney cortex and liver and to a smaller extent in the small intestine. The major substrates for gluconeogenesis include pyruvate, lactate, glycerol, odd chain fatty acids, propionate and amino acids except for lysine and leucine. The majority of the pathway is simply a reversible reaction of glycolysis. The enzymes for gluconeogenesis are present in the cytosol, mitochondria and endoplasmic reticulum (ER) of the tissues in which this pathway is present. Net gluconeogenesis occurs during starvation and after a meal high in fat and protein without carbohydrate.