Tuesday Apr 29, 2025 Cell Respiration I

Aerobic cellular respiration requires oxygen has 4 stages 

1. Glycolysis → 2. Fermentation (anaerobic)

2. Pyruvate oxidation 

3. Citric acid cycle 

4. Oxidative phosphorylation 

Stage 1: Glycolysis 

• Glycolysis is a series of 10 anaerobic chemical reactions that occur in the cytoplasm 

• The starting molecule for glycolysis is a six-carbon molecule glucose (C₆H₁₂O₆)

  • The end products are two three-carbon molecules pyruvate (C₃H₃O₃)

• Can be divided into 3 phases

1. Destabilization: Glucose is prepared for the next two phases by the addition of two phosphate groups 

   1. This process requires an input of two molecules of ATP

      1. Traps glucose inside cell

      2. Destabilizes molecule 

2. Cleavage: 6 carbon glucose split into two identical, 3-carbon sugars (“glyco-lysis”)

3. Pay-off phase: 

   1. Each 3-C glucose derivative is oxidized, NAD+ reduced to NADH (exergonic), coupled to addition of 2nd P to each 3-C sugar (endergonic) 

   2. Added P subsequently removed from each 3-C sugar (exergonic), coupled to phosphorylation of ADP → ATP (endergonic) via substrate-level phosphorylation

   3. Removal of 2nd P, same thing 

• Where are the reactions taking place? Cytoplasm 

• What are the inputs? Glucose, 2 ATP, 2 NAD⁺

• What are the outputs? 4 ATP, 2 NADH, 2 pyruvate 

• What is the ATP “payoff”? 2 net ATP

• Where is the potential energy stored throughout the process? 

  • Chemical bonds 

  • ATP

  • Electron carriers 

Fermentation

• Anaerobic 

• Allows glycolysis to continue in the absence of oxygen

• Pyruvate gets reduced by accepting the electrons from NADH (from glycolysis), converting the electron carrier back to its oxidized form (NAD+)

• This process “replenishes” NAD+ so it can participate in more glycolysis, and thus generate a couple more ATP

• The reduction of pyruvate converts it to either ethanol or lactic acid, depending on pathway/organism 

• Where are the reactions taking place? Cytoplasm 

• What are the inputs? 2 NADH, 2 pyruvate

• What are the outputs? 2 NAD+, 2 EtOH/lactic acid 

• What is the ATP “payoff”? 4 ATP (due to NAD+ oxidation enabling another round of glycolysis)

• Where is the potential energy stored throughout the process? 

  • Chemical bonds 

  • Electron carriers 

  • But cell can’t extract energy from them without O2

The Mitochondria

• In the presence of oxygen each pyruvate can be further broken down to extract more potential energy stored in its chemical bonds 

  • Takes place in the powerhouse of the cell

• Mitochondria have an inner membrane and an outer membrane that define two spaces 

• The space between the two membranes is called the intermembrane space, and the space inside the inner membrane is the mitochondrial matrix 

• Pyruvate oxidation is the first step that takes place inside the mitochondria (in the matrix)

Stage 2: Pyruvate Oxidation 

• The link between glycolysis and citric acid cycle 

• Both pyruvates from glycolysis are transported from cytosol into the mitochondrial matrix, where each is converted to acetyl-CoA

  • First each pyruvate is oxidized, forming CO2 and electrons transferred to NAD+, leaving one acetyl group each (redox)

  • Molecule coenzyme A attaches itself to each acetyl group, forming acetyl-CoA

  • Acetyl-CoA then enters the Citric Acid Cycle for further oxidation (x2)

• Where are the reactions taking place? Mitochondria 

• What are the inputs? 2 Pyruvate, 2 NAD+

• What are the outputs? 2 Acetyl-CoA, 2 NADH, 2 CO2

• What is the ATP “payoff”? None (this is an intermediary step)

• Where is the potential energy stored throughout the process? 

  • Chemical bonds 

  • Electron carriers 

Stage 3: Citric acid cycle 

• It is called a cycle because the starting molecule (oxaloacetate) is regenerated 

• Consists series of enzymatic reactions in the mitochondrial matrix that systematically break down (oxidize) acetyl-CoA, abstracting all electrons from its bonds (it’s completely oxidized) 

  • (so all that’s left of the original glucose molecule after the Citric Acid Cycle is 2 CO2 that we exhale) 

• All the electrons taken from acetyl-CoA get transferred to the electron carriers NADH and FADH2 (and a P1 is added to ADP to make 1 ATP via substrate-level phosphorylation) 

  • (note: for each glucose molecule there are 2 rounds of Citric Acid Cycle)

• Where are the reactions taking place? Mitochondria 

• What are the inputs? 2 Acetyl-CoA (1 per cycle)

• What are the outputs? 2 ATP, 6 NADH, 2 FADH2, 2 CO2

• What is the ATP “payoff”? 2 ATP (1 per cycle) 

• Where is the potential energy stored throughout the process? 

  • ATP 

  • Electron carriers 

Electron Carriers

• If ATP is our goal, why bother with electron carriers? (Why not just directly transfer free energy from glucose into ATP?)

• ATP is a perfectly sized packet of readily available energy that can be used right away for a rx

  • We can make it directly via substrate-level phosphorylation as way to get some quick ATP, but not that efficient 

• Thick of the electrons donated to NADH and FADH2 as more of an investment