Regulation of Glycolysis Enzymes

Protein Digestion and Absorption

• Pepsin:
  • An endopeptidase active at pH 1-2
  • Cleaves peptide bonds after aromatic AAs from N-terminus
• Pancreatic peptidases:
  • Endopeptidases: trypsin, chymotrypsin (cleaves aromatic AAs), and elastase (cleaves small AAs)
  • Important for protein digestion and absorption

Carbohydrate Metabolism

Glycolysis

• The full oxidation of glucose yields a significant amount of energy
• A catabolic process converting glucose to pyruvate via many enzymes
• Takes place in the cytosol of every cell, especially in the brain and muscles
• Divided into two phases: preparatory and payoff phases
• Preparatory phase: glucose => glyceraldehyde 3-phosphate + dihydroxyacetone phosphate
• Committed step: fructose 6-phosphate converted into fructose 1,6-bisphosphate
• Payoff phase: glyceraldehyde 3-phosphate + dihydroxyacetone phosphate converted into pyruvate
• Rate-limiting steps: glucose converted into glucose 6-phosphate by hexokinase, and fructose 6-phosphate converted into fructose 1,6-bisphosphate by phosphofructokinase-1
• Energy-yielding steps: glyceraldehyde-3-P oxidation, ATP synthesis by phosphoglycerate kinase, and ATP synthesis in the last step of glycolysis
• Fate of pyruvate: converted into acetyl-CoA in aerobic conditions, and into lactate in anaerobic conditions
• Regulation of glycolysis: hexokinase, glucokinase, and phosphofructokinase-1 are regulated by various molecules, including insulin, glucose, and ATP

Gluconeogenesis

• The synthesis of glucose from non-carbohydrate precursors
• Takes place primarily in the liver and to a small extent in the renal cortex and enterocytes
• Follows the same pathway as glycolysis, except for reversible reactions and no ATP generation
• Animals can produce glucose from lactate, amino acids, and glycerol

Glycogen Metabolism

• Place of action: primarily in the liver and muscles, in the cytosol
• Function of glycogen in muscles: energy source
• Function of glycogen in liver: regulates blood glucose levels
• Glycogenesis: making glycogen from glucose
• Glycogenolysis: breakdown of glycogen for quick energy release
• Regulation of glycogen synthesis and degradation: glycogen phosphorylase and glycogen synthase are regulated by allosteric and hormonal mechanisms

Anaerobic Glycolysis and Buffer Systems

• Anaerobic glycolysis = lactic acid fermentation
• Reduction of pyruvate into lactate under anaerobic conditions
• Occurs in vigorously contracting muscles and erythrocytes
• Lactate levels are a predictor for cancer patient survival
• Regulation of anaerobic glycolysis: stimulated by increased NADH/H+, anaerobic conditions, and breakdown of ethanol; inhibited by high lactate levels
• Buffer systems maintain blood pH levels
• Acidosis: blood pH < 7.45
• Hemoglobin buffer system deals with O2 and CO2 levels in erythrocytes