Difficulty: Intermediate | Prerequisites: Chapter 7 (membrane transport), Chapter 8 (metabolism, enzymes, ATP, redox basics).
Cellular respiration is how cells extract usable energy from glucose. It runs through three stages (glycolysis, Krebs cycle, and the electron transport chain with chemiosmosis), producing a theoretical maximum of 38 ATP per glucose molecule. This chapter ties together the metabolic and enzyme concepts from Ch. 8 and the membrane transport concepts from Ch. 7, since the electron transport chain depends on a proton gradient across the inner mitochondrial membrane.
Glucose is broken down in three stages. Glycolysis (cytoplasm, anaerobic) splits glucose into 2 pyruvate, netting 2 ATP and 2 NADH. The Krebs cycle (mitochondrial matrix, aerobic) processes acetyl CoA and produces 2 ATP, 6 NADH, 2 FADH2, and 4 CO2. The electron transport chain and chemiosmosis (inner mitochondrial membrane, aerobic) convert the electron carriers into roughly 34 ATP, for a grand total of about 38 ATP.
Cellular respiration
The process of breaking down glucose through chemical reactions to produce ATP. In simple terms, it is how cells turn food into usable energy.
Glycolysis
The first stage of cellular respiration, occurring in the cytoplasm. Splits one 6-carbon glucose into two 3-carbon pyruvate molecules. Does not require oxygen (anaerobic).
Pyruvate
The 3-carbon end product of glycolysis. Must be converted to acetyl CoA before entering the Krebs cycle.
Acetyl CoA
A 2-carbon molecule formed when pyruvate loses a carbon (as CO2) during the transition reaction. This is the fuel that enters the Krebs cycle.
Krebs cycle (citric acid cycle)
The second major stage, occurring in the mitochondrial matrix. A cyclic series of 8 reactions that fully oxidises acetyl CoA, producing NADH, FADH2, ATP, and CO2. Also called the citric acid cycle.
Electron transport chain (ETC)
A series of protein complexes (I through IV) embedded in the inner mitochondrial membrane. Electrons from NADH and FADH2 are passed along the chain, releasing energy that pumps protons into the intermembrane space.
Chemiosmosis
The flow of protons (H+) back through ATP synthase, driven by the concentration gradient built by the ETC. This flow powers the synthesis of ATP from ADP and Pi.
Oxidative phosphorylation
The combined process of the electron transport chain and chemiosmosis. It produces the majority of ATP during cellular respiration (approximately 34 ATP).
NADH
A key electron carrier. Picks up electrons during glycolysis and the Krebs cycle and delivers them to Complex I of the ETC.
FADH2
A second electron carrier. Delivers electrons to Complex II of the ETC. Produces slightly fewer ATP than NADH because it enters the chain later.
Redox reactions
Reactions involving the transfer of electrons. Oxidation is the loss of electrons; reduction is the gain. In simple terms: OIL RIG (Oxidation Is Loss, Reduction Is Gain).
ATP synthase
The enzyme complex in the inner mitochondrial membrane that synthesises ATP as protons flow through it down their concentration gradient.
Fermentation
An anaerobic pathway that regenerates NAD+ from NADH so glycolysis can continue when oxygen is absent. Produces only the 2 ATP from glycolysis.
Substrate-level phosphorylation
Direct transfer of a phosphate group from a substrate molecule to ADP, forming ATP. Occurs in glycolysis and the Krebs cycle.
Location: cytoplasm. Oxygen required: no (anaerobic).
2 ATP are invested to break one glucose (6C) into 2 molecules of PGAL (G3P)
Each PGAL is oxidised: 2 hydrogens transfer to NAD+, producing 2 NADH total
4 ATP are generated by substrate-level phosphorylation
Net gain per glucose: 2 ATP + 2 NADH
End product: 2 pyruvate (3C each)
Location: mitochondrial matrix. Oxygen required: yes (aerobic).
Transition reaction (the bridge between glycolysis and Krebs):
Each pyruvate loses one carbon as CO2 and is converted to acetyl CoA (2C)
2 NADH are produced (one per pyruvate)
This step runs twice per glucose (once for each pyruvate)
Krebs cycle (8 main steps, runs twice per glucose):
Step 1: Acetyl CoA (2C) combines with oxaloacetate (4C) to form citrate (6C)
Steps 2 through 8: Citrate is progressively broken back down to oxaloacetate, releasing CO2 and transferring electrons to carriers
Net gain per glucose (both turns combined): 2 ATP, 6 NADH, 2 FADH2, 4 CO2
Location: inner mitochondrial membrane. Oxygen required: yes (aerobic).
This stage converts the NADH and FADH2 accumulated from earlier stages into ATP.
ETC process:
NADH donates electrons to Complex I, producing protons (H+) that are pumped into the intermembrane space
Electrons pass from Complex I to coenzyme Q (ubiquinone, the mobile electron carrier)
CoQ carries electrons to Complex III
Complex III passes electrons to cytochrome c, where reduction occurs (electron gain)
Cytochrome c delivers electrons to Complex IV, where oxidation occurs (electron loss)
At Complex IV, electrons combine with 1/2 O2 and 2 H+ to form H2O (oxygen is the final electron acceptor)
FADH2 enters at Complex II (bypassing Complex I), donates its electrons and H+ to make FAD, and its electrons follow the same path via CoQ onward
Proton pumping:
Complexes I, III, and IV pump protons from the matrix into the intermembrane space
This creates a higher concentration of H+ (positive charge) in the intermembrane space relative to the matrix
Chemiosmosis:
The proton concentration gradient drives H+ back through ATP synthase
ATP synthase uses this flow to combine ADP with Pi, producing ATP
Net gain from ETC + chemiosmosis: approximately 34 ATP
Stage | ATP produced | Location |
|---|---|---|
Glycolysis | 2 (net) | Cytoplasm |
Krebs cycle | 2 | Mitochondrial matrix |
ETC + Chemiosmosis | ~34 | Inner mitochondrial membrane |
Total | ~38 |
Students often think glycolysis requires oxygen. It does not; glycolysis is anaerobic and occurs in the cytoplasm.
The "38 ATP" figure is a theoretical maximum. In practice, some energy is lost to heat and membrane leakage, so the real yield is closer to 30 to 32 ATP. However, 38 is the number used in this course.
Oxygen does not participate until the very end of the ETC (Complex IV). Its sole role is to accept the spent electrons and combine with H+ to form water.
FADH2 produces fewer ATP than NADH because it enters the chain at Complex II, bypassing Complex I and therefore pumping fewer protons.
⚠️ The essay question asks you to explain how 38 ATP are formed. You need to trace the ATP yield through all three stages with specific numbers.
⚠️ Know the location of each stage: glycolysis in the cytoplasm, Krebs in the matrix, ETC on the inner mitochondrial membrane.
⚠️ Be able to explain the role of NADH and FADH2 as electron carriers and where each enters the ETC.
⚠️ Understand chemiosmosis: the proton gradient drives ATP synthase. This concept reappears in photosynthesis (Ch. 10).
⚠️ The Krebs cycle is also called the citric acid cycle. Know both names.
True or False: Glycolysis occurs in the mitochondria. (False, it occurs in the cytoplasm.)
Fill in the blank: The net ATP gain from glycolysis is ____. (2)
True or False: Oxygen is the final electron acceptor in the ETC. (True)
Fill in the blank: Pyruvate is converted to ______ before entering the Krebs cycle. (Acetyl CoA)
True or False: FADH2 enters the ETC at Complex I. (False, it enters at Complex II.)
Q: In detail, explain how 38 ATP are formed during cellular respiration.
A: Cellular respiration proceeds through three stages. Glycolysis (cytoplasm, anaerobic) splits glucose into 2 pyruvate, investing 2 ATP and producing 4 ATP and 2 NADH, for a net gain of 2 ATP and 2 NADH. During the transition reaction, each pyruvate is converted to acetyl CoA, releasing CO2 and producing 2 NADH total. The Krebs cycle (mitochondrial matrix, aerobic) runs twice per glucose and produces 2 ATP, 6 NADH, 2 FADH2, and 4 CO2. The electron transport chain (inner mitochondrial membrane) accepts electrons from NADH (at Complex I) and FADH2 (at Complex II). Electrons pass through Complexes III and IV via coenzyme Q and cytochrome c, with energy released at each step used to pump protons into the intermembrane space. At Complex IV, electrons combine with oxygen to form water. Chemiosmosis then drives the accumulated protons through ATP synthase, generating approximately 34 ATP. Total: 2 + 2 + 34 = 38 ATP.
Q: Compare aerobic and anaerobic respiration.
A: Aerobic respiration requires oxygen and includes all three stages (glycolysis, Krebs cycle, ETC/chemiosmosis), producing up to 38 ATP per glucose. Anaerobic respiration (fermentation) occurs without oxygen, using only glycolysis and producing just 2 ATP. Fermentation regenerates NAD+ so glycolysis can continue.
Q: What is the role of oxygen in cellular respiration?
A: Oxygen serves as the final electron acceptor at Complex IV of the ETC. It accepts spent electrons and combines with H+ ions to form water. Without oxygen, the ETC stalls, protons cannot be pumped, and oxidative phosphorylation stops.
This chapter is the catabolic counterpart to Chapter 10 (Photosynthesis). Photosynthesis builds glucose; cellular respiration breaks it down. Both use chemiosmosis and an electron transport chain, but in different organelles (chloroplast vs mitochondria) and with different energy sources.
The membrane transport concepts from Chapter 7 underpin the proton gradient and ATP synthase mechanism. The enzyme and activation energy concepts from Chapter 8 explain why each step requires a specific enzyme.
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