8.3 Cellular Respiration

Electron Transport and Energy Production

Cellular respiration is how cells break down nutrients (primarily glucose) to generate ATP, the molecule that drives nearly every energy-requiring process in the cell. The process involves a series of linked pathways, and the electron transport system is where the vast majority of ATP actually gets made.

Electron transport system in cells

The electron transport system (ETS) is a series of protein complexes and electron carriers embedded in a membrane. Its job is to pass electrons from carriers like NADH and FADH$_2$ through a chain of redox reactions, using the released energy to pump protons ($H^+$) across the membrane. This builds up a proton gradient that ultimately drives ATP synthesis.

Where the ETS sits depends on the cell type:

• Prokaryotic cells (bacteria, archaea): The ETS is embedded in the cytoplasmic membrane, since prokaryotes lack mitochondria.
• Eukaryotic cells (animals, plants, fungi): The ETS is embedded in the inner mitochondrial membrane, along the folds called cristae. This membrane's large surface area allows for more ETS complexes and greater ATP output.

Substrate-level vs. oxidative phosphorylation

Cells make ATP in two fundamentally different ways, and it's worth understanding how they compare.

Substrate-level phosphorylation produces ATP directly. An enzyme transfers a phosphate group from a high-energy substrate (like phosphoenolpyruvate or 1,3-bisphosphoglycerate) straight onto ADP. No membrane, no oxygen, no electron transport chain required. This happens during:

• Glycolysis (in the cytoplasm)
• The Krebs cycle (in the mitochondrial matrix for eukaryotes, cytoplasm for prokaryotes)

Oxidative phosphorylation produces ATP indirectly through the ETS and chemiosmosis. Electron carriers (NADH and FADH$_2$) donate their electrons to the ETS, which pumps protons to build a gradient. Protons then flow back through ATP synthase, which harnesses that flow to make ATP.

• Requires oxygen as the final electron acceptor in aerobic respiration
• Accounts for roughly 34 of the ~38 ATP generated per glucose molecule during aerobic respiration
• Far more efficient than substrate-level phosphorylation, which is why aerobic organisms produce so much more ATP

Chemiosmosis and proton motive force

Chemiosmosis is the mechanism that links the ETS to ATP production. Here's how it works:

1. The ETS uses energy from electron transfers to pump $H^+$ ions across the membrane (into the intermembrane space in eukaryotes, or outside the cytoplasmic membrane in prokaryotes).
2. This creates a high concentration of $H^+$ on one side of the membrane and a low concentration on the other.
3. Protons flow back down their concentration gradient through ATP synthase, and the energy of that flow drives ATP synthesis.

The force that pushes protons through ATP synthase is called the proton motive force (PMF). It has two components:

• Chemical gradient ($\Delta pH$): the difference in $H^+$ concentration across the membrane
• Electrical gradient (membrane potential): the charge difference created by the buildup of positive ions on one side

Together, these two forces provide the energy that ATP synthase needs to combine ADP and inorganic phosphate ($P_i$) into ATP.

ATP synthase in cellular respiration

ATP synthase is the enzyme that actually makes ATP during oxidative phosphorylation. Think of it as a molecular turbine: protons flowing through it cause part of the enzyme to physically rotate, and that rotation drives a conformational change that catalyzes the reaction $ADP + P_i \rightarrow ATP$.

• In prokaryotes, ATP synthase sits in the cytoplasmic membrane alongside the ETS components.
• In eukaryotes, it sits in the inner mitochondrial membrane, protruding into the mitochondrial matrix where ATP is released.

The key point: ATP synthase doesn't use the electrons directly. It uses the proton gradient that the ETS built. Without that gradient, ATP synthase has no driving force.

Aerobic and Anaerobic Respiration

Aerobic vs. anaerobic respiration

The difference between aerobic and anaerobic respiration comes down to what accepts the electrons at the end of the transport chain.

Aerobic respiration uses $O_2$ as the final electron acceptor. Oxygen picks up the "spent" electrons (along with $H^+$) and forms water. This is the most efficient form of respiration because oxygen has a very high affinity for electrons, which means the ETS can extract maximum energy as electrons pass through.

The three main stages of aerobic respiration:

1. Glycolysis (cytoplasm): Glucose is split into two pyruvate molecules, yielding 2 ATP and 2 NADH.
2. Krebs cycle (mitochondrial matrix): Acetyl-CoA is fully oxidized, producing $CO_2$, 1 ATP (as GTP), 3 NADH, and 1 FADH$_2$ per turn. Since each glucose produces two acetyl-CoA, the cycle turns twice.
3. Oxidative phosphorylation (inner mitochondrial membrane): NADH and FADH$_2$ feed electrons into the ETS, generating approximately 34 ATP via chemiosmosis.

Total yield: approximately 38 ATP per glucose (though the actual number in eukaryotic cells is often closer to 30–32 due to transport costs across mitochondrial membranes).

Anaerobic respiration still uses an electron transport chain, but substitutes a different final electron acceptor in place of oxygen. Common alternatives include:

• Nitrate ($NO_3^-$), reduced to nitrite or nitrogen gas
• Sulfate ($SO_4^{2-}$), reduced to hydrogen sulfide ($H_2S$)
• Fumarate, reduced to succinate

These acceptors have lower electron affinity than $O_2$, so less energy is released per electron transferred, and fewer ATP are produced overall.

Fermentation is distinct from anaerobic respiration because it does not use an electron transport chain at all. Instead, fermentation regenerates $NAD^+$ by transferring electrons from NADH to an organic molecule, allowing glycolysis to keep running. The ATP yield is limited to what glycolysis produces (2 ATP per glucose).

Two common types:

• Lactic acid fermentation: Pyruvate is reduced to lactate. Found in certain bacteria (like Lactobacillus) and in human muscle cells during intense exercise.
• Ethanol fermentation: Pyruvate is converted to acetaldehyde, then reduced to ethanol, releasing $CO_2$. Found in yeasts like Saccharomyces cerevisiae.

Key metabolic intermediates in cellular respiration

These three molecules connect the major stages of cellular respiration:

• Pyruvate: The 3-carbon end product of glycolysis. In aerobic conditions, pyruvate enters the mitochondria and is converted to acetyl-CoA by pyruvate dehydrogenase, releasing one $CO_2$ and generating one NADH per pyruvate.
• Acetyl-CoA: A 2-carbon acetyl group attached to coenzyme A. It enters the Krebs cycle by combining with the 4-carbon molecule oxaloacetate to form citrate. Acetyl-CoA is also a convergence point for fat and protein metabolism, not just carbohydrate breakdown.
• Citrate (citric acid): The 6-carbon molecule formed at the start of the Krebs cycle. Through a series of oxidation and decarboxylation reactions, citrate is progressively broken down, regenerating oxaloacetate and producing the electron carriers (NADH, FADH$_2$) that feed the ETS.