The Krebs Cycle Step by Step: Carbon Counts, Products and NEET Yield
Glycolysis ends with pyruvate and a modest profit of 2 ATP, yet a cell can extract far more energy from the same glucose. Where does the rest come from? The answer is a circular pathway inside the mitochondrion, the Krebs cycle (also called the citric acid cycle or TCA cycle), and it is a favourite of NEET Biology because its numbers can be tested in a dozen different ways.
Quick Summary
The cycle runs in the mitochondrial matrix and starts when acetyl-CoA (2 carbons) joins oxaloacetate (4 carbons) to make citrate (6 carbons).
Each turn releases 2 CO₂ and regenerates oxaloacetate, so the cycle can keep running.
Each turn yields 3 NADH, 1 FADH₂ and 1 GTP (or ATP) by substrate-level phosphorylation.
One glucose gives two acetyl-CoA, so everything is counted twice per glucose.
Exam relevance: NEET only.
Where the cycle begins: from pyruvate to acetyl-CoA
Pyruvate made in the cytoplasm enters the mitochondrion. There, pyruvate dehydrogenase removes one carbon as CO₂, reduces one NAD⁺ to NADH, and attaches the remaining two-carbon acetyl group to coenzyme A. This step, called the link reaction or oxidative decarboxylation, produces acetyl-CoA. It is not part of the cycle itself, but it feeds it. Fats and proteins also reach the cycle as acetyl-CoA or as cycle intermediates, which is why the Krebs cycle is called the common pathway for oxidising all food.
The cycle, step by step
Think of the cycle as a machine that takes in a two-carbon fragment and strips it of its energy in small instalments. Follow the carbon count and the story becomes easy to remember.
Condensation: acetyl-CoA (2C) + oxaloacetate (4C) → citrate (6C), catalysed by citrate synthase. Coenzyme A is released.
Isomerisation: citrate is rearranged through cis-aconitate to isocitrate (6C) by aconitase.
First oxidative decarboxylation: isocitrate → α-ketoglutarate (5C). One CO₂ is lost and one NADH forms.
Second oxidative decarboxylation: α-ketoglutarate → succinyl-CoA (4C). Another CO₂ is lost and another NADH forms.
Substrate-level phosphorylation: succinyl-CoA → succinate (4C). The energy of the CoA bond makes one GTP (ATP in many textbooks) directly, with no electron transport chain involved.
Dehydrogenation: succinate → fumarate. FAD is reduced to FADH₂. The enzyme, succinate dehydrogenase, is the only one embedded in the inner mitochondrial membrane.
Hydration: fumarate → malate, by adding water (fumarase).
Final dehydrogenation: malate → oxaloacetate (4C), producing the third NADH. The cycle is now ready for the next acetyl-CoA.
Notice that the two CO₂ molecules lost come from the carbons of the incoming citrate, and the carbon count returns to 4 exactly where it began. That is why oxaloacetate is called a catalyst-like carrier: it is never used up, only regenerated.
Why the cycle needs oxygen even though oxygen is not in it
No step above uses O₂ directly. But NADH and FADH₂ must give their electrons to the electron transport chain to become NAD⁺ and FAD again. With no oxygen to accept those electrons at the end of the chain, NAD⁺ runs out and the dehydrogenation steps stall. So the cycle is aerobic indirectly. This is one of the most frequently tested ideas.
Worked example: counting the yield
Question: How many ATP equivalents come from one turn of the cycle, and how many from the full oxidation of one glucose starting at pyruvate, using the values 2.5 ATP per NADH and 1.5 ATP per FADH₂?
One turn (one acetyl-CoA):
3 NADH × 2.5 = 7.5 ATP
1 FADH₂ × 1.5 = 1.5 ATP
1 GTP = 1 ATP
Total = 7.5 + 1.5 + 1 = 10 ATP
One glucose gives 2 pyruvate, hence 2 acetyl-CoA, hence 2 turns. The cycle gives 2 × 10 = 20 ATP. The two link reactions add 2 NADH × 2.5 = 5 ATP. So pyruvate-onward oxidation contributes 25 ATP, plus 4 CO₂ from the two turns and 2 CO₂ from the link reactions: 6 CO₂ in all, the 6 carbons of glucose.
Many NCERT-based questions use the older values of 3 ATP per NADH and 2 per FADH₂, which gives 3×3 + 2 + 1 = 12 ATP per turn. Always read which convention the question follows.
Mistakes students actually make
Forgetting to double: quoting 3 NADH per glucose instead of 6 from the cycle.
Counting the link reaction NADH as part of the cycle. It is made outside the cycle proper.
Saying ATP is produced by oxidative phosphorylation in the cycle. The only direct phosphorylation is at succinyl-CoA → succinate.
Placing the whole pathway in the cytoplasm. In eukaryotes it is in the matrix, with succinate dehydrogenase in the inner membrane.
Mixing up the carbon counts: citrate 6C, α-ketoglutarate 5C, succinyl-CoA 4C.
How NEET asks it
Match the following: enzyme or substrate against carbon number or product.
"Which step produces FADH₂?" or "Where does substrate-level phosphorylation occur?"
Count questions: NADH, FADH₂, CO₂ or ATP per glucose or per acetyl-CoA.
Assertion-reason on why the cycle stops without oxygen.
Location questions: matrix versus inner membrane versus cytoplasm.
Pro Tip: Memorise the cycle as a story of carbon counts, 4 → 6 → 6 → 5 → 4 → 4 → 4 → 4 → 4, and attach the products to it: the two decarboxylations are the two steps where the carbon count falls (6 → 5 → 4), and each is paired with an NADH. Once you know that, the rest, one GTP, one FADH₂ and the last NADH, fall into the four-carbon steps. You can rebuild the whole table in 20 seconds in the exam hall, and as we stress in our NEET revision sessions at Sukriti NeetJee, a skeleton you can rebuild beats a list you merely memorised.
Frequently Asked Questions
Is the Krebs cycle aerobic or anaerobic?
It is aerobic in the practical sense. No step consumes O₂ directly, but the NAD⁺ and FAD it needs are regenerated only when the electron transport chain passes electrons to oxygen. Without oxygen, the cycle shuts down.
How many CO₂ molecules are released per glucose?
Each turn of the cycle releases 2 CO₂, so two turns release 4. The link reaction releases 1 CO₂ per pyruvate, adding 2. The total is 6 CO₂, matching the six carbons of glucose.
Why is it called a cycle?
Because oxaloacetate, the molecule that accepts acetyl-CoA in the first step, is regenerated in the last step. A small amount of it can therefore process an unlimited number of acetyl groups.
Where exactly does the cycle occur?
In the mitochondrial matrix. The exception is succinate dehydrogenase, which sits in the inner mitochondrial membrane and links the cycle directly to the electron transport chain.
What is substrate-level phosphorylation in the cycle?
It is the direct transfer of a phosphate to GDP (or ADP) using the energy released when succinyl-CoA becomes succinate. No proton gradient is used. It happens once per turn.
Is the Krebs cycle also an anabolic pathway?
Yes, it is amphibolic. Intermediates such as α-ketoglutarate and oxaloacetate are drawn off to make amino acids, and succinyl-CoA is used in heme synthesis, while the cycle also breaks down food molecules.
Stuck on a step or a count? Drop your doubt in the comments, and share this with a fellow NEET aspirant who keeps losing marks on respiration.
Comments