Biochemistry ATP Generation Mechanisms

Generating ATP

• Two Mechanisms:
  • Substrate-level Phosphorylation:
    • Occurs during glycolysis and citric acid cycle.
    • Uses enzyme/substrate interaction.
    • ADP + P → ATP
  • Oxidative Phosphorylation:
    • Takes place within the mitochondria.
    • Requires coenzymes, electrons (H), and oxygen.
    • Electron Transport Chain (ETC):
      • Electrons are shuttled, releasing energy to pump H+ ions.
      • Creates an electrical gradient across the inner mitochondrial membrane.
    • Chemiosmosis:
      • H+ ions are allowed back across the membrane, generating energy for ATP synthesis.
      • The number of H+ ions used determines the total ATP production.

Oxidation-Reduction Reactions

• Oxidation: Loss of electrons from an atom or molecule.
  • Glucose is oxidized, losing H and its electrons.
• Reduction: Gain of electrons.
  • Electron recipient is reduced.
  • Oxygen is reduced, gaining electrons to form water.
• Coenzymes:
  • FAD (Flavin Adenine Dinucleotide):
    • Derivative of Vitamin B2.
    • Accepts two hydrogen atoms from the TCA cycle.
    • Gains two electrons to become FADH2.
  • NAD (Nicotinamide Adenine Dinucleotide):
    • Derivative of Vitamin B3.
    • Accepts two hydrogen atoms.
    • Gains two electrons to become NADH.

Forming ATP

• Oxidative Phosphorylation:
  • Allows slow, gradual release of ATP to prevent cell "explosion."
  • Uses energy from electrons in the electron transport chain to form protons (H+).
• Reactive Oxygen Species (ROS):
  • High energy electrons are dangerous.
  • Form superoxides and hydrogen peroxide.
  • Contribute to aging, disease, and cancer.
  • Antioxidants bind electrons to decrease these effects.
  • Cells utilize oxygen to bind electrons to form the O2- ion, which combines with 2H+ to form H2O.

Glycolysis

• Location: Cytoplasm
• Final Products:
  • 2 molecules of pyruvic acid.
  • 2 molecules of NADH (go to mitochondria for OXPHOS).
  • 4 molecules of ATP (net gain of 2) via substrate-level phosphorylation.
• Pyruvic Acid:
  • With oxygen: continues to the Citric Acid (Krebs) Cycle.
  • Without oxygen: NADH "dumps" H+ onto pyruvic acid, forming lactic acid or ethyl alcohol.

Transition Step (Reaction)

• Location: Mitochondrial matrix.
• Converts pyruvic acid into acetyl CoA.
• Steps:
  • Removal of C and 2 O forming CO2.
  • Removal of H forming NADH.
  • Acetic acid + coenzyme A = acetyl CoA.

Citric Acid (Krebs) Cycle (CAC)

• Location: Mitochondrial matrix.
• Begins with the formation of citric acid from acetyl CoA (derived from pantothenic acid).
• Steps:
  • Acetyl CoA + oxaloacetic acid → citric acid (citrate).
  • Citric acid continues through the cycle, removing carbons to form CO2.
  • One ATP molecule is formed via substrate-level phosphorylation.
  • Each acetyl CoA produces:
    • 2 CO2 molecules
    • 3 NADH2 molecules
    • 1 FADH2 molecules
    • 1 ATP molecule.
• Per Glucose Molecule:
  • 6 CO2 molecules
  • 8 NADH molecules
  • 2 FADH2 molecules
  • 2 ATP molecules.

Oxidative Phosphorylation

• Location: Inner mitochondrial membrane.
• Directly uses oxygen.
• Consists of two processes:
  • Electron Transport Chain (ETC).
  • Chemiosmosis.

Electron Transport Chain (ETC)

• Location: Inner mitochondrial membrane.
• NADH and FADH2 deliver H+ and electrons.
• Electrons are split and shuttled, generating energy used for H+ pumping into the intermembrane space.
• Creates an H+ gradient.
• Components:
  • Cytochromes: proteins with a heme group and Fe (cyt b, cyt a).
  • Coenzyme Q: non-protein carrier.
• Energy from the electrons is used to pump H+ into the intermembrane space.

Chemiosmosis

• Location: Inner mitochondrial membrane.
• ATP synthesis occurs when H+ diffuses back into the matrix through ATP synthase.
• ATP synthase uses the energy of protons to make ATP.
• ATP Yield:
  • Each NADH provides energy to pump 10 H+ into the intermembrane space.
  • Every 4 H+ traversing ATP synthase generates 1 ATP.
• Efficiency:
  • Oxidation of each NADH = 2.5 ATP.
  • Oxidation of each FADH2 = 1.5 ATP.

Aerobic Cellular Respiration - Summary

• Total ATP Production from one glucose molecule:
  • Glycolysis:
    • 2 ATP via substrate-level phosphorylation............. 2
    • 2 NADH (ETC: X 2.5)............................. 5
  • Transition Reaction:
    • 2 NADH (ETC: X 2.5)............................. 5
  • Citric Acid Cycle:
    • 3 NADH X 2 = 6 NADH2 (ETS: X 2.5 in ETC)........... 15
    • 1 FADH2 X 2 = 2 FADH2 (ETS: X 1.5 in ETC)........... 3
    • 1 ATP X 2 via substrate-level phosphorylation)....... 2
  • Total: 32-38 ATP