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  1. GLUCONEOGENESIS Dr. Gamal Gabr, College of Pharmacy

  2. GLUCONEOGENESIS • Gluconeogenesis, the formation of new glucose molecules from non-carbohydrate precursors, occurs primarily in the liver. • Precursor molecules include lactate, pyruvate, glycerol, and certain α-keto acids (molecules derived from amino acids). • When liver glycogen is depleted (e.g., owing to prolonged fasting or vigorous exercise), the gluconeogenesis pathway provides the body with adequate glucose. • Brain and red blood cells rely exclusively on glucose as their energy source. Dr. Gamal Gabr, College of Pharmacy

  3. Gluconeogenesis Reactions • The reaction sequence in gluconeogenesis is largely the reverse of glycolysis. • three glycolytic reactions (the reactions catalyzed by hexokinase, PFK-1, and pyruvate kinase) are irreversible. • In gluconeogenesis, alternate reactions catalyzed by different enzymes are used to bypass these reactions. Dr. Gamal Gabr, College of Pharmacy

  4. Gluconeogenesis Reactions Dr. Gamal Gabr, College of Pharmacy

  5. Gluconeogenesis Reactions • 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 substrates 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). Dr. Gamal Gabr, College of Pharmacy

  6. Gluconeogenesis Reactions • 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. Dr. Gamal Gabr, College of Pharmacy

  7. Gluconeogenesis Regulation • The rate of gluconeogenesis is affected by substrate availability, allosteric effectors, and hormones. • Gluconeogenesis is stimulated by high concentrations of lactate, glycerol, and amino acids. • A high-fat diet, starvation, and prolonged fasting make large quantities of these molecules available. • The four key enzymes in gluconeogenesis (pyruvate carboxylase, PEP carboxykinase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase) are affected to varying degrees by allosteric modulators. • For example, fructose-1,6-bisphosphatase is activated by citrate and inhibited by AMP and fructose-2,6-bisphosphate. Dr. Gamal Gabr, College of Pharmacy

  8. Gluconeogenesis Regulation Dr. Gamal Gabr, College of Pharmacy