Glycolysis + TCA

• Glycolysis

  Pathway that converts glucose to pyruvate
• TCA cycle


  Tricarboxylic acid cycle (also known as Krebs cycle)
• Acetyl-CoA


  Molecule that carries acetyl group to TCA cycle
• Energy balance sheet


  1. 2 ATPs used to prime glycolysis

  2. 4 ATPs produced from glycolytic pathway

  3. 6 ATPs from re-oxidation of 2 NADHs

  4. 8 ATPs net gained from conversion of glucose to pyruvate
• Glycolysis


  1. Hexose sugar phosphorylated at both ends

  2. Conversion to GAP

  3. Oxidation and phosphorylation with Pi

  4. Results in triose phosphorylated at both ends

  5. 4 ATP generated
• Cofactor (coenzyme)


  • Binds to apoenzyme and changes structure to allow catalysis
  • Needs to regenerate to participate in reaction again
• Structure of NAD binding site of alcohol dehydrogenase from Pseudomonas aeruginosa
• Glyceraldehyde-3-phosphate dehydrogenase

  1. NAD+ reduced to NADH

  2. Glyceraldehyde-3-phosphate oxidised to 1,3-bisphosphoglycerate

  3. Phosphorylation is endergonic but coupled to NAD+ reduction
• Glyceraldehyde-3-phosphate dehydrogenase

  1. Formation of covalent thioether bond with substrate

  2. Oxidation of thioether to thioester using NAD+

  3. Cleavage of thioester bond drives endergonic phosphorylation
• Glycolysis requires continual supply of NAD+
• Aerobic conditions


  • Oxidation of NADH by electron transport chain
  • Pyruvate enters TCA cycle
• Anaerobic conditions


  • Conversion of pyruvate to lactate
  • All pyruvate must be converted to lactate for ATP synthesis to continue
• Anaerobic respiration leading to lactate


  1. Carboxylate|Carbonyl|Methyl

  2. Carboxylate|Hydroxyl|Methyl

  3. Lactate dehydrogenase
• Red blood cells lack mitochondria so can only use lactic acid pathway
• Anaerobic respiration leading to alcohol


  1. Pyruvate decarboxylase

  2. Alcohol dehydrogenase

  3. Acetaldehyde
• Under anaerobic conditions, only 2 ATP produced per glucose
• Prokaryotic vs Eukaryotic

  • Prokaryotic: Glycolysis in cytoplasm, TCA in cytoplasm, ETC in cell membrane, Fermentation in cytoplasm
  • Eukaryotic: Glycolysis in cytoplasm, TCA in mitochondria, ETC in mitochondrial membrane, Fermentation in cytoplasm
• Fate of Pyruvate - Aerobic conditions (eukaryotic)


  1. Pyruvate enters mitochondria via MPC

  2. Pyruvate converted to acetyl-CoA in mitochondrial matrix
• Porins


  Proteins in outer mitochondrial membrane that allow small molecules like pyruvate to enter intermembrane space
• Mitochondrial pyruvate carrier (MPC)


  Transports pyruvate across impermeable inner mitochondrial membrane
• Pyruvate dehydrogenase complex


  1. Oxidative decarboxylation of pyruvate to acetyl-CoA

  2. NAD+ reduced to NADH

  3. CO2 released
• Coenzyme A (CoA)


  • Acetyl carrying group that forms thioesters
  • Involved in both catabolic and anabolic processes
• Multi-enzyme complex

  Group of enzymes associated in a particular metabolic pathway
• Pyruvate oxidation steps


  1. Carboxyl group snipped off, releasing CO2

  2. Two-carbon molecule oxidised, reducing NAD+ to NADH

  3. Oxidised two-carbon molecule (acetyl group) attached to CoA to form acetyl-CoA
• Two pyruvates from glycolysis converted to two acetyl-CoA, releasing two CO2 and generating two NADH
• In eukaryotes, pyruvate dehydrogenase is located in the mitochondrial matrix
• Glycolysis occurs in the cytoplasm of cells and does not require oxygen.
• The net result of glycolysis is the production of two molecules of pyruvate, which can be further oxidized to produce ATP.
• Pyruvic acid is produced from glucose during glycolysis.
• The citric acid cycle takes place in the mitochondria and requires oxygen.
• Oxidative phosphorylation occurs in the mitochondria and requires oxygen.