Glycolysis

• Glucose enters glycolysis as a six-carbon sugar (glucose) and exits as three-carbon sugars (pyruvic acid).
• The net gain from glycolysis is two ATP molecules per glucose molecule.
• Glycolysis is the first step in cellular respiration, which converts glucose into pyruvate.
• In aerobic conditions, pyruvate can be further oxidized to produce more energy through the citric acid cycle and electron transport chain.
• Fermentation produces lactic acid when oxygen levels are low, such as during intense exercise.
• Glycolysis occurs in the cytoplasm, while fermentation can occur in either the cytoplasm or mitochondria.
• Lactic acid buildup causes muscle fatigue and soreness.
• In aerobic conditions, pyruvate is further oxidized to carbon dioxide through the citric acid cycle and electron transport chain.
• Glucagon reduces the concentration of fructose 2,6-bisphosphate
• Fructose 2,6-bisphosphate is the most important regulatory factor for controlling PFK
• Fructose 2,6-bisphosphate allosterically inhibits phosphofructokinase and activates fructose 1,6-bisphosphatase, favoring increased gluconeogenesis
• 2,3 DPG combines with hemoglobin and reduces Hb affinity with oxygen
• In the presence of 2,3-BPG, oxyhemoglobin unloads more oxygen to the tissues
• Cori’s cycle:

  • Lactate created by anaerobic glycolysis in muscles is transported to the liver
  • Transformed to glucose in the liver
  • Glucose is metabolized back to lactate in the muscles
  • Important in the regeneration of NAD+ required in glycolysis
• Rate-limiting step in glycolysis:

  • Phosphorylation of Fructose 6-phosphate to fructose 1,6-bisphosphate by phosphofructokinase (PFK)
  • PFK is an allosteric enzyme regulated by allosteric effectors
• Isocitrate is formed from citrate via cis-aconitate in the matrix of the mitochondria by aconitase
• Lactic acid produced in red blood cells is converted to pyruvate during gluconeogenesis
• PEP is formed from pyruvate in gluconeogenesis by pyruvate carboxylase converting pyruvate to oxaloacetate and then phosphoenolpyruvate carboxykinase converting oxaloacetate to PEP
• Components of the electron transport chain:

  • Complex I
  • Complex II
  • Coenzyme Q
  • Complex III
  • Cytochrome C
  • Complex IV
• Inhibitors of the electron transport chain:

  • Rotenone inhibits NADH and coenzyme Q
  • Antimycin inhibits the site between cytochrome b and c1
  • Carbon monoxide, cyanide, and azide inhibit cytochrome oxidase
• Substrate-level phosphorylation is the synthesis of a nucleotide from a non-nucleotide molecule
• Oxidative phosphorylation is the phosphorylation of ADP to ATP using free energy produced from redox reactions in the electron transport chain
• Glucose 6-phosphate dehydrogenase deficiency leads to red blood cell lysis due to impaired NADPH synthesis
• Activation of glucose for glycogenesis involves the synthesis of UDP-glucose stimulated by insulin
• Fate of pyruvate:

  • Under anaerobic conditions, pyruvate is reduced to lactate
  • Under aerobic conditions, pyruvate is oxidized to acetyl CoA
• Branching enzyme in glycogen synthesis is glucosyl-4-6 transferase
• Debranching enzyme cleaves branches of glycogen using glycosyl 4:4 transferase and glucosidase
• Insulin stimulates glycolysis and inhibits gluconeogenesis
• Glucagon reduces fructose 2,6-bisphosphate concentration, favoring gluconeogenesis
• Cytosolic glycerol 3-phosphate dehydrogenase oxidizes NADH to NAD+ in the glycerol phosphate shuttle, generating 2 ATP in the ETC
• PPP provides NADPH in erythrocytes for detoxification and regeneration of glutathione
• Two oxidative reactions in the uronic acid pathway:

  • Formation of UDP-glucuronate
  • Oxidation of L-Gulonate
  • Ascorbate is not produced in humans due to the absence of L-gulonolactone oxidase
• The glycerol phosphate shuttle plays a critical role in several aspects:
• Energy production:

  • Particularly significant in tissues with high energy requirements, like skeletal muscles and the brain
  • Facilitates the indirect transfer of electrons from NADH to the electron transport chain, ultimately contributing to ATP generation
• NAD+/NADH balance:

  • Helps maintain the optimal balance between NAD+ and NADH within the cell
  • Essential for the smooth functioning of glycolysis, as NAD+ is required for the continuous conversion of glucose into pyruvate
• Alternative pathway:

  • Serves as an alternative pathway for NADH oxidation when the malate-aspartate shuttle is inactive
  • The malate-aspartate shuttle is another mechanism for transporting electrons across the mitochondrial membrane
• The conversion of fructose 1,6 bisphosphate to fructose 6-phosphate is the second bypass in a metabolic pathway
• The reversal of the reaction catalyzed by phosphofructokinase is effected by fructose 1,6 bisphosphatase
• Fructose 1,6 bisphosphatase:

  • Is Mg2+ dependent
  • Promotes the irreversible hydrolysis of the C-1 phosphate, resulting in the conversion of Fructose 1,6-bisphosphate to Fructose 6-phosphate + Pi
• The conversion of glucose 6-phosphate to free glucose is the third pass in the metabolic pathway