Aerobic respiration: Krebs’ cycle and ETS

Aerobic respiration

In plain words: glycolysis only cuts glucose in half. In the mitochondria, the halves are taken apart completely. The matrix strips off every hydrogen atom and loads it, as electrons, onto carrier molecules (NADH and FADH_₂), releasing the carbon as CO_₂. The inner membrane then cashes in those carriers: it passes the electrons down a chain to oxygen and uses the energy to make most of the cell’s ATP.

Pyruvate to acetyl CoA

• For aerobic respiration, pyruvate, the final product of glycolysis, is transported from the cytoplasm into the mitochondria (NCERT page 158).
• In the mitochondrial matrix, pyruvate undergoes oxidative decarboxylation by a complex set of reactions catalysed by pyruvic dehydrogenase, which need several coenzymes, including NAD^⁺ and coenzyme A (page 158):

pyruvic acid + CoA + NAD^⁺ → acetyl CoA + CO_₂ + NADH + H^⁺ (pyruvate dehydrogenase, with Mg^²⁺)

• One glucose gives two pyruvic acid molecules, so this step makes two NADH per glucose (page 158).
• Acetyl CoA then enters the tricarboxylic acid (TCA) cycle, more commonly called the Krebs’ cycle after Hans Krebs, who first worked it out (page 158).

The tricarboxylic acid cycle

The cycle (NCERT pages 158–159):

1. The acetyl group condenses with oxaloacetic acid (OAA) and water to give citric acid, catalysed by citrate synthase; a molecule of CoA is released.
2. Citrate is isomerised to isocitrate.
3. Two successive decarboxylations follow, giving α-ketoglutaric acid and then succinyl-CoA.
4. Succinyl-CoA is oxidised, in the remaining steps, back to OAA, so the cycle continues. When succinyl-CoA becomes succinic acid, a molecule of GTP is made: this is substrate-level phosphorylation. In a coupled reaction, GTP gives its phosphate to ADP, making ATP.

In each turn, NAD^⁺ is reduced to NADH + H^⁺ at three points and FAD to FADH_₂ at one point. To keep the cycle running, OAA must be continually replenished, and NAD^⁺ and FAD must be regenerated from NADH and FADH_₂ (page 159).

NCERT’s Figure 12.3 goes from succinic acid straight to malic acid (page 159). Beyond the NCERT text, there is an intermediate: succinate dehydrogenase converts succinate to fumarate, and fumarase then converts fumarate to malate (MedlinePlus Genetics, US National Library of Medicine, SDHA gene; FH gene).

NCERT writes the oxidised form of FAD as “FAD^⁺” (page 159). NCERT’s own summary equation for this phase balances in charge only if the oxidised form carries no charge, so read it as FAD, which is reduced to FADH_₂ (reasoned from NCERT’s equation, page 159).

NCERT’s summary equation for this phase, per pyruvic acid (page 159), with FAD for NCERT’s FAD^⁺:

pyruvic acid + 4NAD^⁺ + FAD + 2H_₂O + ADP + Pi → 3CO_₂ + 4NADH + 4H^⁺ + FADH_₂ + ATP (mitochondrial matrix)

So, for one glucose, the conversion of pyruvate to acetyl CoA and the TCA cycle release CO_₂ and make 8 NADH + H^⁺, 2 FADH_₂ and just 2 ATP. Oxygen has not yet appeared, and neither has the promised large number of ATP (NCERT page 159).

Electron transport system and oxidative phosphorylation

• The energy stored in NADH + H^⁺ and FADH_₂ is released when they are oxidised through the electron transport system (ETS) and the electrons are passed to O_₂, forming water. The ETS is in the inner mitochondrial membrane (NCERT page 159).
• Complex I, NADH dehydrogenase, oxidises NADH from the matrix and passes the electrons to ubiquinone, inside the membrane. Ubiquinone also receives reducing equivalents from FADH_₂ through complex II, generated when succinate is oxidised in the TCA cycle (NCERT page 160).
• Reduced ubiquinone (ubiquinol) passes its electrons through the cytochrome bc_₁ complex (complex III) to cytochrome c, a small protein on the outer surface of the inner membrane that acts as a mobile carrier between complexes III and IV (page 160).
• Complex IV, cytochrome c oxidase, contains cytochromes a and a_₃ and two copper centres (page 160).
• As the electrons pass through complexes I, III and IV, protons are moved out of the matrix into the intermembrane space: NCERT Figure 12.4 shows 4, 4 and 2 H^⁺; complex II moves none. This proton gradient drives ATP synthase. NCERT’s photosynthesis chapter notes that in respiration protons accumulate in the intermembrane space of the mitochondria (NCERT Chapter 11, page 140).
• As the electrons pass through complexes I to IV, the flow is coupled to ATP synthase (complex V), which makes ATP from ADP and inorganic phosphate. Oxidation of one NADH gives 3 ATP; one FADH_₂ gives 2 ATP (page 160).
• Oxygen acts only at the end, as the final hydrogen acceptor, but it is vital, since it drives the whole process by removing hydrogen from the system (page 160).
• In photophosphorylation, light energy builds the proton gradient; in respiration, the energy of oxidation-reduction does, so the process is called oxidative phosphorylation (page 160).

Beyond the NCERT text: the observed yields are closer to about 2.5 ATP per NADH and 1.5 per FADH_₂ (Wikipedia, “Citric acid cycle”, facts in our words), but NCERT uses 3 and 2; give NCERT’s values in NEET answers.

ATP synthase: F_₀ and F_₁

• ATP synthase (complex V) has two major parts, F_₁ and F_₀ (NCERT page 161).
• F_₁, the headpiece, is a peripheral membrane protein complex and contains the site for synthesis of ATP from ADP and inorganic phosphate (page 161).
• F_₀ is an integral membrane protein complex that forms the channel through which protons cross the inner membrane (page 161).
• The passage of protons through F_₀ is coupled to the catalytic site of F_₁. For each ATP produced, 4 H^⁺ pass through F_₀, from the intermembrane space to the matrix, down the electrochemical proton gradient (page 161).

Beyond the NCERT text: the number of protons per ATP depends on the ring of c subunits in F_₀, which turns as protons pass. Wikipedia’s article “Cellular respiration” gives 8 c subunits in vertebrates; with 3 ATP made per turn, that is about 8 ÷ 3 ≈ 2.7 H^⁺ through the synthase per ATP, and about one more H^⁺ is spent moving ADP, phosphate and ATP across the inner membrane (facts in our words). In NEET answers, use NCERT’s 4 H^⁺ per ATP.

The mechanism is the chemiosmotic one you met in photosynthesis, where the chloroplast’s own ATP synthase has parts called CF_₀ and CF_₁ (NCERT Chapter 11, page 142); there, protons flow from the thylakoid lumen to the stroma. For the membranes and matrix, see mitochondria.

Solved examples

Common mistakes to avoid

Quick revision summary

• Pyruvate enters the mitochondria; pyruvate dehydrogenase (with NAD^⁺, CoA, Mg^²⁺) turns it into acetyl CoA, CO_₂ and NADH + H^⁺ in the matrix.
• TCA (Krebs’) cycle in the matrix: acetyl CoA + OAA → citric acid (citrate synthase) → isocitrate → α-ketoglutaric acid → succinyl-CoA → succinic acid (GTP, then ATP) → … → OAA; 3 NADH and 1 FADH_₂ per turn.
• Per glucose, pyruvate → acetyl CoA and TCA: 6 CO_₂, 8 NADH, 2 FADH_₂, 2 ATP.
• ETS on the inner membrane: complex I (NADH dehydrogenase) → ubiquinone (also from FADH_₂ via complex II) → complex III (cytochrome bc_₁) → cytochrome c → complex IV (cytochrome c oxidase) → O_₂, the final hydrogen acceptor; NADH gives 3 ATP, FADH_₂ 2 ATP: oxidative phosphorylation.
• ATP synthase: F_₀ channel in the membrane, F_₁ headpiece makes ATP; 4 H^⁺ per ATP, intermembrane space to matrix.

Questions students ask

Why is the Krebs’ cycle also called the TCA cycle and the citric acid cycle?

The Krebs’ cycle, the tricarboxylic acid (TCA) cycle and the citric acid cycle are three names for one cycle: NCERT calls it the tricarboxylic acid cycle, “more commonly called as Krebs’ cycle after the scientist Hans Krebs who first elucidated it” (page 158). It is the citric acid cycle because citric acid is the first compound the cycle makes (NCERT page 158), and NCERT Figure 12.3 is titled “The Citric acid cycle” (page 159). Beyond the NCERT text, “tricarboxylic” refers to citric acid and isocitric acid, each of which carries three carboxyl (–COOH) groups, as their chemical names, propane-1,2,3-tricarboxylic acids with one hydroxyl group, show.

How many times does the Krebs’ cycle turn for one glucose molecule?

The Krebs’ cycle turns twice for each glucose molecule: glycolysis splits glucose into two pyruvic acid molecules, and each gives one acetyl CoA, which enters the cycle (NCERT pages 155 and 158). Each turn has two decarboxylations, releasing 2 CO_₂, reduces NAD^⁺ at three points and, in NCERT’s words, FAD^⁺ (strictly FAD) at one, and makes one GTP (pages 158–159), so the two turns give 4 CO_₂, 6 NADH + H^⁺, 2 FADH_₂ and 2 ATP. The Calvin cycle, by contrast, turns six times to build one glucose, once for each CO_₂ fixed (NCERT Chapter 11, page 145; the Calvin cycle).

What is the difference between the Krebs’ cycle and the electron transport chain?

The Krebs’ cycle and the electron transport chain are successive stages of aerobic respiration in different parts of the mitochondrion: the cycle, in the matrix, oxidises acetyl CoA, releasing CO_₂ and loading its hydrogen onto NAD^⁺ and FAD (NCERT’s FAD^⁺), while the electron transport system (NCERT’s name for the chain), in the inner membrane, takes the electrons from NADH + H^⁺ and FADH_₂ and passes them to O_₂, forming water (NCERT pages 158–159). The cycle uses no O_₂ itself and makes just one ATP, from GTP, per turn by substrate-level phosphorylation, whereas the chain’s electron flow is coupled to ATP synthase, which makes 3 ATP per NADH and 2 per FADH_₂ by NCERT’s count (pages 159–160).

What is the difference between the electron transport chain and oxidative phosphorylation?

The electron transport chain and oxidative phosphorylation are linked parts of one process: the chain (NCERT’s ETS) passes electrons from NADH + H^⁺ and FADH_₂ to O_₂, and oxidative phosphorylation is the making of ATP by ATP synthase, driven by the proton gradient this electron flow builds (NCERT pages 159–161). It is called oxidative because the energy of oxidation-reduction, not light as in photophosphorylation, builds it (page 160); the mechanism is the chemiosmotic hypothesis.

Is the link reaction part of the Krebs’ cycle?

No, the link reaction is a separate step just before the Krebs’ cycle: in the mitochondrial matrix, each pyruvic acid from glycolysis undergoes oxidative decarboxylation to acetyl CoA, giving off one CO_₂ and forming one NADH + H^⁺, and only the acetyl CoA enters the cycle (NCERT page 158). It is an oxidative decarboxylation because pyruvic acid both loses carbon as CO_₂ and gives up hydrogen to NAD^⁺, and it makes no ATP directly. NCERT includes the step in its Figure 12.3 but does not use the name, which comes from the way the step links glycolysis in the cytoplasm to the cycle in the matrix.

Which chapter is the Krebs’ cycle in, and is it in the NEET syllabus?

The Krebs’ cycle is in NCERT Biology Class 11, Chapter 12, Respiration in Plants, Section 12.4.1, “Tricarboxylic Acid Cycle” (pages 158–159), and it is in the NEET (UG) 2026 syllabus, whose Unit 4, Plant Physiology, lists “Cellular respiration-glycolysis, fermentation (anaerobic), TCA cycle and electron transport system (aerobic)”. The same unit also lists “Energy relations - Number of ATP molecules generated”, which is NCERT’s respiratory balance sheet.

Practice questions

Try each question first, then open the answer to check your working.

1. Q1. Which enzyme catalyses the conversion of pyruvate to acetyl CoA?

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   Pyruvic (pyruvate) dehydrogenase (NCERT page 158).

2. Q2. With which compound does the acetyl group condense at the start of the TCA cycle, and what is formed?

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   Oxaloacetic acid (OAA), with water; citric acid is formed, by citrate synthase (NCERT page 158).

3. Q3. What is the final hydrogen acceptor in aerobic respiration?

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   Oxygen (NCERT page 160); NCERT’s Summary also calls O_₂ the ultimate acceptor of electrons, reduced to water (page 165).