3.5 Cellular Respiration

Cellular respiration is how cells harvest energy from macromolecules (like glucose) to make ATP. In eukaryotes it’s three main stages: glycolysis (in the cytosol) breaks glucose into pyruvate, generating ATP and NADH; pyruvate oxidation and the Krebs (citric acid) cycle in the mitochondrial matrix release CO2 and produce more NADH and FADH2; and the electron transport chain (ETC) on the inner mitochondrial membrane passes those electrons to oxygen, pumping protons into the intermembrane space. That proton gradient (high outside, low inside across the inner membrane/cristae) drives ATP synthase by chemiosmosis—this oxidative phosphorylation makes most ATP. Without oxygen, fermentation regenerates NAD+ so glycolysis can continue (less ATP). For AP you should know structures (matrix, cristae, inner membrane), roles of NADH/FADH2, proton gradient, and that oxidative phosphorylation is coupled to the ETC; you don’t need to memorize every enzyme step. Review Topic 3.5 ideas in the unit review (https://library.fiveable.me/ap-biology/unit-3) and practice problems (https://library.fiveable.me/practice/ap-biology).

Mitochondria have folded inner membranes called cristae so you can make more ATP. The inner membrane holds the electron transport chain (ETC) and ATP synthase; folding increases surface area, so more ETC complexes and ATP synthase fit per mitochondrion (CED EK 3.5.A.3.ii). As NADH and FADH2 donate electrons, the ETC pumps protons from the matrix into the intermembrane space, creating a proton (H+) gradient (electrochemical gradient). Protons flow back through ATP synthase by chemiosmosis, driving oxidative phosphorylation to make ATP (CED EK 3.5.A.3.iii). More cristae = bigger proton gradient capacity = more ATP per glucose. If you want a compact review of related energy concepts for AP Bio, check the unit 3 study guide (https://library.fiveable.me/ap-biology/unit-3/photosynthesis/study-guide/qIyyKCxB3XJI9oRI7yjl), the unit overview (https://library.fiveable.me/ap-biology/unit-3), or practice problems (https://library.fiveable.me/practice/ap-biology).

Short answer: both start with glycolysis, but cellular respiration fully oxidizes pyruvate (via pyruvate oxidation, Krebs cycle, and an electron transport chain in mitochondria) to make lots of ATP by creating a proton gradient and doing oxidative phosphorylation; fermentation instead happens when oxygen (or another terminal electron acceptor) isn’t available, so cells keep glycolysis going by recycling NADH back to NAD⁺ and produce small organic products (lactic acid or alcohol) and much less ATP (EKs 3.5.A.1, 3.5.B.4–6). Key differences: respiration uses an ETC and proton gradient across the inner mitochondrial membrane (cristae) to drive ATP synthase; fermentation does not use an ETC or chemiosmosis. On the AP exam, you should know these process-level differences and keywords (NADH, FADH₂, ETC, chemiosmosis, oxidative phosphorylation, glycolysis, fermentation) but you won’t need to memorize every enzyme or step (see CED EKs). For a concise review, check the Topic 3 study guide (photosynthesis link also covers energetics) (https://library.fiveable.me/ap-biology/unit-3/photosynthesis/study-guide/qIyyKCxB3XJI9oRI7yjl) and more unit resources (https://library.fiveable.me/ap-biology/unit-3). For extra practice, try the 1,000+ AP problems (https://library.fiveable.me/practice/ap-biology).

Glycolysis is a cytosolic pathway (it happens in the cell’s cytosol) that breaks one glucose into two pyruvate molecules and captures energy as ATP and NADH (EK 3.5.B.1). It makes ATP by substrate-level phosphorylation: enzyme-catalyzed reactions transfer a phosphate group directly from a phosphorylated intermediate to ADP, forming ATP (this is different from oxidative phosphorylation in mitochondria). Glycolysis also reduces NAD+ to NADH; those NADH (and later FADH2 from the Krebs cycle) feed electrons to the ETC for more ATP, if oxygen is present (EK 3.5.B.2, 3.5.B.4). If no oxygen’s available, fermentation regenerates NAD+ so glycolysis can continue (EK 3.5.B.6). The AP Exam expects you to know that glycolysis yields ATP, NADH, and pyruvate and occurs in the cytosol, but you don’t need to memorize every step or enzyme. For a quick unit review, see the Topic 3 study guide (https://library.fiveable.me/ap-biology/unit-3/photosynthesis/study-guide/qIyyKCxB3XJI9oRI7yjl); more practice problems are at (https://library.fiveable.me/practice/ap-biology).

The Krebs (citric acid) cycle’s point is to extract high-energy electrons from pyruvate so the cell can make lots of ATP via oxidative phosphorylation. In the mitochondrial matrix, organic carbon from pyruvate is gradually oxidized; electrons are transferred to NAD⁺ and FAD to form NADH and FADH₂ (these ferry electrons to the ETC in the inner mitochondrial membrane). CO₂ is produced because oxidation of organic carbon removes carbon atoms as CO₂—that’s the carbon being lost when the fuel is broken down. Those released electrons (via NADH/FADH₂) drive the proton gradient across the inner membrane and ATP synthase makes most of the cell’s ATP (oxidative phosphorylation). Remember: AP doesn’t require memorizing every cycle step, but you should know where it happens (matrix), products (ATP, NADH, FADH₂, CO₂), and role in feeding the ETC. For unit review check the Unit 3 page (https://library.fiveable.me/ap-biology/unit-3) and practice problems (https://library.fiveable.me/practice/ap-biology).

Think of the ETC like a downhill conveyor for electrons that powers a proton pump. NADH and FADH₂ (from glycolysis/Krebs) donate high-energy electrons to protein carriers in the inner mitochondrial membrane (folded into cristae for more surface area). As electrons pass down the chain through a series of redox reactions toward the terminal acceptor O₂, that energy is used to pump protons from the matrix into the intermembrane space, creating a high H+ concentration outside and low inside (an electrochemical/proton gradient). Protons then flow back through ATP synthase by chemiosmosis—that flow drives ADP + Pi → ATP (oxidative phosphorylation). If the chain is uncoupled, electrons still move but ATP production drops and heat is released. This matches the AP CED: focus on gradients, NADH/FADH₂ delivery, ATP synthase, and O₂ as the terminal acceptor. For more review, see the Topic 3 study guides (unit overview: https://library.fiveable.me/ap-biology/unit-3; study guide: https://library.fiveable.me/ap-biology/unit-3/photosynthesis/study-guide/qIyyKCxB3XJI9oRI7yjl) and practice questions (https://library.fiveable.me/practice/ap-biology).

NADH and FADH2 both shuttle electrons from glycolysis/pyruvate oxidation and the Krebs cycle to the electron transport chain, but they enter the chain at different points. NADH donates electrons earlier (from the matrix side), so its electrons pass through more proton-pumping complexes across the inner mitochondrial membrane—this builds a larger proton gradient in the intermembrane space. FADH2 donates electrons a bit later, so fewer protons are pumped. Because the proton gradient drives ATP synthase (chemiosmosis/oxidative phosphorylation), NADH generally yields more ATP per electron pair (~2.5 ATP) than FADH2 (~1.5 ATP). Having both carriers lets cells capture electrons released at different steps of metabolism (EK 3.5.B.2–4; EK 3.5.A.3 in the CED) and maximize energy harvest. For review, check Unit 3 materials (https://library.fiveable.me/ap-biology/unit-3) and practice problems (https://library.fiveable.me/practice/ap-biology). For related topic review, see the Topic 3 study guide (https://library.fiveable.me/ap-biology/unit-3/photosynthesis/study-guide/qIyyKCxB3XJI9oRI7yjl).

ATP synthase uses the proton gradient from the ETC to do mechanical/chemical work (chemiosmosis → oxidative phosphorylation). Protons build up in the intermembrane space (high [H+]) and flow back into the matrix through the membrane-embedded F0 portion of ATP synthase. That proton flow turns a rotor (c-ring + central stalk), which physically rotates the F1 “knob.” Rotation forces conformational changes in F1’s catalytic beta subunits that cycle through three states (bind ADP + Pi, synthesize ATP, release ATP). So the energy of H+ moving down its electrochemical gradient is converted into rotation, then into the bond energy of ATP from ADP + Pi. This is exactly what EK 3.5.A.3(iii) describes on the AP CED. For quick review of related Unit 3 ideas (membranes, chemiosmosis), check the unit overview (https://library.fiveable.me/ap-biology/unit-3), the Topic 3 study guide linked above (https://library.fiveable.me/ap-biology/unit-3/photosynthesis/study-guide/qIyyKCxB3XJI9oRI7yjl), and run more practice problems at (https://library.fiveable.me/practice/ap-biology).

If no oxygen is available, the electron transport chain (ETC) in the inner mitochondrial membrane can’t pass electrons to O2, so oxidative phosphorylation and the Krebs cycle slow or stop because NADH and FADH2 can’t be reoxidized. Glycolysis still runs, but only produces 2 net ATP per glucose. To keep glycolysis going, cells use fermentation (EK 3.5.B.6): pyruvate is converted to other organic molecules that regenerate NAD+ from NADH. In animals and some microbes that yields lactic acid (lactic acid fermentation); in yeast and some bacteria it yields ethanol + CO2 (alcoholic fermentation). Fermentation doesn’t make more ATP beyond glycolysis—it just recycles electron carriers so the cell can survive short-term without O2. For AP review, this matches EK 3.5.A/B (glycolysis, NADH, ETC, fermentation). More unit review is at the Unit 3 overview (https://library.fiveable.me/ap-biology/unit-3) and practice problems (https://library.fiveable.me/practice/ap-biology).

Mitochondria make the electrochemical gradient with the electron transport chain (ETC) on the inner mitochondrial membrane. Electrons from NADH and FADH₂ (made in glycolysis and the Krebs cycle) are passed along a series of membrane proteins; as electrons move, those proteins pump H⁺ (protons) from the matrix into the intermembrane space. That builds two things: a concentration difference (more H⁺ outside the inner membrane) and an electrical difference (outside is more positive), together called a proton (electrochemical) gradient. The inner membrane’s folds (cristae) increase surface area so more ETC complexes and ATP synthase fit there. ATP synthase lets H⁺ flow back into the matrix (chemiosmosis) and uses that energy to make ATP from ADP + Pi (oxidative phosphorylation). (This matches EK 3.5.A.2–3 and EK 3.5.B.5.) For extra practice and review, check the Topic 3 study guide (https://library.fiveable.me/ap-biology/unit-3/photosynthesis/study-guide/qIyyKCxB3XJI9oRI7yjl) and practice problems (https://library.fiveable.me/practice/ap-biology).

Because the electron transport chain (ETC) in the inner mitochondrial membrane pumps H+ from the matrix into the intermembrane space (IMS), the IMS ends up with a higher proton concentration (lower pH) while the matrix has fewer H+ (higher pH). The inner membrane is largely impermeable to protons, so that electrochemical (proton) gradient is maintained across the membrane and stored as potential energy. Cristae increase inner-membrane surface area so more ETC complexes can pump protons. When protons flow back into the matrix through ATP synthase (chemiosmosis), that proton-motive force drives ATP synthesis (oxidative phosphorylation). This is exactly what EK 3.5.B.3–5 describes: electron transfer builds a proton gradient and matrix pH is higher than the intermembrane space. For a quick unit review, check the Unit 3 overview (https://library.fiveable.me/ap-biology/unit-3) and practice problems (https://library.fiveable.me/practice/ap-biology). The Topic 3.5 ideas tie into that Topic 3 study guide (https://library.fiveable.me/ap-biology/unit-3/photosynthesis/study-guide/qIyyKCxB3XJI9oRI7yjl).

Cells harvest glucose’s chemical energy in steps so it’s useful. First, glycolysis in the cytosol breaks glucose into pyruvate, making a little ATP and reducing NAD+ to NADH (EK 3.5.B.1). Pyruvate enters mitochondria and is further oxidized in the Krebs (citric acid) cycle in the matrix, releasing CO2, more ATP, and lots of high-energy electrons carried by NADH and FADH2 (EK 3.5.B.2–3). Those electrons go to the electron transport chain in the inner mitochondrial membrane (cristae), driving proton pumping into the intermembrane space and creating an electrochemical (proton) gradient (EK 3.5.A.3i–ii; EK 3.5.B.5). Protons flow back through ATP synthase (chemiosmosis), powering ATP synthesis—this is oxidative phosphorylation (EK 3.5.A.3iii). If oxygen is absent, fermentation regenerates NAD+ so glycolysis can continue (EK 3.5.B.6). Review this chain of events and organelle structure in the unit 3 study materials (https://library.fiveable.me/ap-biology/unit-3) and the Topic 3.5 study guide linked above (https://library.fiveable.me/ap-biology/unit-3/photosynthesis/study-guide/qIyyKCxB3XJI9oRI7yjl). For extra practice questions, use (https://library.fiveable.me/practice/ap-biology).

Oxidative phosphorylation and substrate-level phosphorylation both make ATP, but they work very differently. - Oxidative phosphorylation: electrons from NADH/FADH2 travel through the ETC in the inner mitochondrial membrane, pumping H+ into the intermembrane space to make a proton gradient. Protons flow back through ATP synthase (chemiosmosis) and that flow powers ATP production. It’s coupled to electron transport and depends on a terminal electron acceptor (usually O2)—this is the process described in EK 3.5.A.3 (iii). - Substrate-level phosphorylation: an enzyme transfers a phosphate directly from a high-energy substrate molecule to ADP to make ATP. This happens in glycolysis (cytosol) and in the Krebs cycle (mitochondrial matrix). It doesn’t require the ETC or O2. For AP prep, memorize where each happens (glycolysis, Krebs vs. inner membrane/ATP synthase) and the role of proton gradients (CED Topic 3.5). More review: Fiveable’s unit 3 overview (https://library.fiveable.me/ap-biology/unit-3) and the Topic 3 study guide (https://library.fiveable.me/ap-biology/unit-3/photosynthesis/study-guide/qIyyKCxB3XJI9oRI7yjl). For extra practice, try the AP problems page (https://library.fiveable.me/practice/ap-biology).

Photosynthesis and cellular respiration are linked parts of the same energy cycle—photosynthesis captures light energy to build glucose and O2, while cellular respiration breaks glucose down to make ATP and returns CO2 and H2O. In AP terms: photosynthesis stores energy in organic molecules; cellular respiration (glycolysis → pyruvate oxidation → Krebs cycle → ETC/oxidative phosphorylation) extracts electrons (NADH, FADH₂) and uses an electron transport chain to build a proton gradient across the inner mitochondrial membrane. ATP synthase then makes ATP by chemiosmosis (EK 3.5.A.3 and EK 3.5.B.5). They’re “opposite” because one uses light to reduce CO₂ into sugars and releases O₂, the other oxidizes those sugars back to CO₂ while reducing O₂ to H₂O. For AP review, focus on big-picture flows of energy and electrons (don’t memorize every enzyme); see the photosynthesis study guide (https://library.fiveable.me/ap-biology/unit-3/photosynthesis/study-guide/qIyyKCxB3XJI9oRI7yjl) and unit overview (https://library.fiveable.me/ap-biology/unit-3). For extra practice, check the 1,000+ AP problems (https://library.fiveable.me/practice/ap-biology).

Fermentation is used when cells can’t use the full aerobic pathway—either because oxygen (the usual terminal electron acceptor) isn’t available or because the organism lacks an electron transport chain/mitochondria. Glycolysis still makes a small amount of ATP, but it also reduces NAD+ to NADH. Fermentation regenerates NAD+ (by reducing pyruvate to lactate or ethanol), letting glycolysis keep running so ATP keeps being produced. That’s beneficial because it: 1) lets organisms survive and produce ATP in anoxic environments (anaerobic bacteria, yeast, muscle cells during intense exercise), 2) provides rapid ATP for short bursts (muscle), and 3) yields useful byproducts (lactic acid, ethanol) important ecologically and for humans. This fits AP CED LO 3.5.A/B—respiration and fermentation are both characteristic of life, and fermentation specifically allows glycolysis to proceed without oxygen (EK 3.5.A.1; EK 3.5.B.6). For review, check the unit overview (https://library.fiveable.me/ap-biology/unit-3) and more practice problems (https://library.fiveable.me/practice/ap-biology).