Cellular Respiration: Transition State, Citric Acid Cycle, Oxidative Phosphorylation

The Transition State: Pyruvate to Acetyl-CoA

• Location: Glycolysis occurs in the cytosol. For further steps, pyruvate must enter the mitochondria.
• Pyruvate Transport into Mitochondria:
  • Pyruvate first enters the intermembrane compartment (between the outer and inner mitochondrial membranes) via a channel protein.
  • To enter the inner mitochondrial matrix, pyruvate is transported via secondary active transport using a proton-pyruvate symporter.
    • This symporter moves two molecules ($H^+$ and pyruvate) in the same direction.
    • It uses the passive movement of protons ($H^+$) (down their concentration gradient) to actively pump pyruvate against its concentration gradient into the matrix.
    • This is secondary active transport because it does not directly use $ATP$. If $ATP$ were directly used, it would be primary active transport.
• Conversion to Acetyl-Coenzyme A (Acetyl-CoA):
  • Once in the matrix, pyruvate undergoes a conversion to acetyl-CoA.
  • Enzyme: Pyruvate dehydrogenase (name not required for memorization).
  • Process:
    1. A carboxyl group is removed from pyruvate, released as carbon dioxide ($CO_2$).
    2. The remaining two-carbon molecule (acetyl group) is oxidized.
    3. The electrons lost during oxidation are transferred to $NAD^+$ to form $NADH$ (an electron carrier).
    4. The acetyl group is then attached to Coenzyme A, forming Acetyl-Coenzyme A.
  • Net Output per pyruvate: 1 Acetyl-CoA, 1 $CO_2$, 1 $NADH$.
  • Per Glucose Molecule: Since one glucose produces two pyruvate molecules, this transition step occurs twice. Therefore, per glucose, the output is 2 Acetyl-CoA, 2 $CO_2$, and 2 $NADH$.

The Citric Acid Cycle (Krebs Cycle)

• Location: Mitochondrial matrix.
• Purpose: Further oxidize the acetyl group from acetyl-CoA, producing more electron carriers ($NADH$ and $FADH_2$) and some $GTP$.
• Key Steps:
  1. Starting Molecule: The four-carbon molecule oxaloacetate (spelled O-X-A-L-O-A-C-E-T-A-T-E).
  2. First Step/Product: Acetyl-CoA (2 carbons) combines with oxaloacetate (4 carbons) to form the six-carbon molecule citrate. Coenzyme A is released to pick up another acetyl group.
  3. Oxidation: Throughout the cycle, citrate is progressively oxidized, meaning it loses electrons. These electrons are captured by $NAD^+$ to form $NADH$ and by $FAD$ to form $FADH_2$.
  4. Carbon Loss: Over the course of the cycle, two carbon atoms are lost as $CO_2$ (the two carbons that entered as acetyl-CoA).
  5. Energy Production: The cycle produces $GTP$ (guanosine triphosphate), which is functionally equivalent to $ATP$ (adenosine triphosphate) – it's a modified RNA nucleotide where guanine replaces adenine.
• Net Output per Acetyl-CoA (and thus per cycle):
  • 2 $CO_2$
  • 3 $NADH$
  • 1 $FADH_2$
  • 1 $GTP$
• Net Output per Glucose Molecule: Since two acetyl-CoA molecules enter the cycle per glucose, all outputs listed above are doubled.

Oxidative Phosphorylation: Electron Transport Chain and Chemiosmosis

• Overall Process: This is the final stage of aerobic respiration, where the energy stored in $NADH$ and $FADH_2$ is used to produce a large amount of $ATP$.
• Three Main Steps:
  1. Oxidation of $NADH$ and $FADH_2$ (Electron Transport Chain).
  2. Pumping of protons ($H^+$) to establish an electrochemical gradient.
  3. Chemiosmosis: $ATP$ synthesis via $ATP$ synthase.

1. Electron Transport Chain (ETC)

• Location: Inner mitochondrial membrane.
• Function: A series of protein complexes that accept electrons from $NADH$ and $FADH_2$ and pass them sequentially.
• Electron Donation:
  • $NADH$ donates its electrons to the first protein complex in the chain.
  • $FADH_2$ donates its electrons to the second protein complex in the chain.
• Electron Flow: Electrons are passed from one protein complex to the next, similar to high-energy electrons