Glucose Metabolism

• Conditions for liver cell to promote glycolysis or gluconeogenesis:

  • Glycolysis: insulin (high blood sugar) and PFK-1
  • Gluconeogenesis: glucagon (low blood sugar), epinephrine, and PFBase-1
• Glycolysis uses glucose to make energy in the form of ATP, producing pyruvate; Gluconeogenesis occurs when the liver is low in glycogen, especially after sleeping or fasting
• Enzymes shared between glycolysis and gluconeogenesis are enolase, phosphoglycerate mutase, phosphoglycerate kinase, glyceraldehyde-3-phosphate dehydrogenase, triose phosphate isomerase, aldolase, and phosphoglucose isomerase; unique enzymes ensure these pathways don't occur simultaneously
• Pyruvate carboxylase converts pyruvate to oxaloacetate using a biotin cofactor, requiring transport into the mitochondria; the reaction occurs in the mitochondria, converting 3C to 4C
• Biotin is a cofactor for pyruvate carboxylase, facilitating the transfer of a carboxyl group in the reaction
• OAA to PEP conversion occurs in the cytosol under aerobic metabolism due to the NADH/NAD+ ratio; in anaerobic conditions, it happens in the mitochondria
• Precursors for gluconeogenesis include glycerol, amino acids, lactate, and carbon fixation; amino acids and lactate are the main C sources
• Glycolysis and gluconeogenesis are reciprocally regulated based on energy needs in the cell; PFK-1 and insulin trigger glycolysis, while FBPase-1 and glucagon trigger gluconeogenesis
• Glucose-6-phosphatase localizes to the lumen of the endoplasmic reticulum in hepatocytes, renal cells, and epithelial cells of the small intestines
• F2,6BP acts as an activator of PFK-1 (glycolysis) and a negative regulator of FBPase-1 (gluconeogenesis); its levels are regulated by insulin and glucagon signaling
• The Cori pathway converts lactate from muscle cells to glucose in the liver through gluconeogenesis, involving pyruvate and lactate conversions
• Glycogen is a stored form of glucose; having multiple non-reducing ends on glycogen makes it more efficient for rebuilding or removal
• Glycogen granules consist of 20-40 glycogen core complexes, each with glycogenin protein and ~50,000 Glu molecules with -1,4 linkage in the main chain and -1,6 branches
• Enzymes for glycogenolysis include glycogen phosphorylase, phosphoglucomutase, and glycogen debranching enzyme; G1P in muscle is kept locally, while in the liver, it is distributed throughout the body
• Enzymes for glycogen synthesis include phosphoglucomutase, UDP-glucose pyrophosphorylase, glycogen synthase, and glycogen branching enzyme
• Glycogenin is an anchor protein for the glycogen core complex, possessing glycosyltransferase and synthase activities
• Glycogen metabolism is regulated by glucose levels, with glycogen phosphorylase and synthase being allosterically regulated; phosphorylation activates glycogen phosphorylase and deactivates glycogen synthase
• Carbohydrate metabolism is regulated by insulin (glycogen synthesis) and glucagon/epinephrine (glycogen breakdown) based on glucose levels
• Phosphorylation activates glycogen phosphorylase and deactivates glycogen synthase
• Insulin promotes glycogen synthesis, while glucagon/epinephrine stimulate glycogen breakdown