Accounting of Energy Molecules & Oxidative Phosphorylation part 5

Energy Harvesting from Glucose

  • The overall goal is to harvest energy from glucose to produce ATP through glycolysis, pyruvate oxidation, citric acid cycle, and oxidative phosphorylation.

Glycolysis

  • A six-carbon glucose molecule is split into two pyruvate molecules.
  • Net yield: 2 ATP molecules (through substrate-level phosphorylation).
  • 2 NADH molecules are produced.
  • NADH produced in glycolysis cannot directly cross the inner mitochondrial membrane.
  • Electrons from NADH are transferred to electron shuttles.
  • Electron shuttles reduce either NAD+ to NADH or FAD to FADH2, depending on the shuttle.

Pyruvate Oxidation

  • Each pyruvate molecule loses one carbon, forming a two-carbon acetyl group that attaches to Coenzyme A (CoA), making Acetyl CoA.
  • 2 NADH molecules are generated.

Citric Acid Cycle (Krebs Cycle)

  • Acetyl CoA feeds into the cycle. The CoA is released, and the acetyl group combines with oxaloacetate.
  • 2 ATP molecules are produced directly.
  • The cycle generates NADH and FADH2 (reduced forms of NAD+ and FAD).
  • NADH and FADH2 carry high-energy electrons to the electron transport chain.

Oxidative Phosphorylation

  • The electron transport chain (ETC) is located in the inner mitochondrial membrane.
  • Electrons from NADH and FADH2 are transferred through the ETC.
  • Electron transfer is coupled with proton pumping, creating a high proton concentration in the intermembrane space compared to the matrix.
  • The proton gradient drives ATP synthase, which produces the bulk of ATP.
  • The number of protons pumped per electron from NADH and FADH2 is not precisely defined, but NADH generally contributes to more proton pumping than FADH2.
  • The majority of ATP is generated through the electron transport chain and ATP synthase.

Mitochondrial Function

  • Oxygen enters the mitochondria to act as the final electron acceptor in the ETC.
  • Carbon dioxide (CO2) generated during the citric acid cycle and pyruvate oxidation exits the mitochondria.
  • Fatty acids can be converted into acetyl groups and enter the citric acid cycle, providing energy from fats.

ATP Production and Usage

  • NADH is oxidized to NAD+ when it donates electrons to the first complex of the ETC.
  • Three of the ETC complexes pump protons across the inner membrane during electron transfer, building the proton gradient.
  • Protons flow down their concentration gradient through ATP synthase, driving ATP production.
  • ATP is transported out of the mitochondria into the cytosol to power cellular processes.
  • The cell maintains an ATP concentration about 10 times higher than ADP.
  • ATP is hydrolyzed to ADP and a phosphate group, releasing energy.
  • ADP and phosphate are transported back into the mitochondrial matrix for ATP regeneration by ATP synthase.
  • A typical ATP molecule is shuttled out of and back into the mitochondrion for recharging more than once per minute.

Fermentation

  • Fermentation occurs when oxygen is insufficient to serve as the final electron acceptor in the electron transport chain.
  • Without oxygen, the electron carriers (NADH and FADH2) cannot release their electrons, leading to a backup in the citric acid cycle and a halt in ATP production via oxidative phosphorylation.
  • Glycolysis does not require oxygen and can continue even when oxygen is limited.
  • Glycolysis requires NAD+ to continue operating (specifically in reaction 6, where glyceraldehyde-3-phosphate is converted).
  • Fermentation regenerates NAD+ from NADH, allowing glycolysis to continue producing a small amount of ATP through substrate-level phosphorylation.

Lactic Acid Fermentation

  • In human muscle cells, lactic acid fermentation occurs when oxygen is scarce.
  • The enzyme lactate dehydrogenase transfers electrons from NADH to pyruvate, producing lactate and regenerating NAD+.

Alcohol Fermentation

  • Yeast performs alcohol fermentation, producing ethanol and CO2.
  • Pyruvate is converted to acetaldehyde, releasing CO2.
  • Acetaldehyde accepts electrons from NADH, forming ethanol and regenerating NAD+.

Metabolic Integration

  • Glycolysis is an interconnected pathway where molecules can be shunted off to build other molecules.
  • Catabolic pathways funnel electrons from various organic molecules into cellular respiration.

Alternative Energy Sources

  • Proteins can be broken down into amino acids.
  • Amino groups are removed (deamination).
  • The remaining molecules are converted into pyruvate, acetyl CoA, or other intermediates of the citric acid cycle.
  • Fats are a major energy source.
  • Glycerol can be converted into glyceraldehyde-3-phosphate (an intermediate in glycolysis).
  • Fatty acid tails are broken down into two-carbon acetyl groups, which enter the citric acid cycle.
  • Fatty acids yield more ATP than glucose due to the large number of acetyl groups that can be generated from their long hydrocarbon tails.

Anabolic Pathways

  • The body uses small molecules (from food or intermediates in glycolysis and the citric acid cycle) to build larger substances.

Summary of Reactants and Products

Glycolysis:

  • Reactants: Glucose, ADP, NAD+
  • Products: Pyruvate (2 molecules), ATP (2 net molecules), NADH (2 molecules)

Pyruvate Oxidation:

  • Reactants: Pyruvate, Coenzyme A, NAD+
  • Products: Acetyl CoA, CO2, NADH

Citric Acid Cycle:

  • Reactants: Acetyl CoA, Oxaloacetate, NAD+, FAD, ADP
  • Products: Citric Acid, CO2, NADH, FADH2, ATP

Electron Transport Chain:

  • Reactants: NADH, FADH2, Oxygen, ADP
  • Products: NAD+, FAD, Water, ATP

Conclusion

  • Knowing the initial reactants and final products of each stage is important for understanding cellular respiration.