In gluconeogenesis, which occurs when blood sugar levels are low and liver glycogen is depleted, 7 of the 10 reactions of glycolysis are reversed. Three irreversible glycolytic reactions are bypassed by alternative reactions. The major s ubstrates for gluconeogenesis are certain amino acids (derived from muscle), lactate (formed in muscle and red blood cells), and glycerol (produced from the degradation of triacylglycerols). In contrast to the reactions of glycolysis, which occur only in cytoplasm, the gluconeogenesis reactions catalyzed by pyruvate carboxylase and, in some species, PEP carboxykinase occur within the mitochondria. The reaction catalyzed by glucose-6-phosphatase takes place in the endoplasmic reticulum. Note that gluconeogenesis and glycolysis do not occur simultaneously. In glycolysis, pyruvate is converted either to acetyl-CoA (not shown) or to lactate.