How to memorize the Krebs cycle

The Krebs cycle in one table

The cycle runs in the mitochondrial matrix and turns once for each acetyl CoA. Here are all 8 steps, numbered as in OpenStax Biology:

Per turn: 2 CO₂, 3 NADH, 1 FADH₂ and 1 GTP or ATP. Per glucose (2 turns): 4 CO₂, 6 NADH, 2 FADH₂ and 2 GTP or ATP.

Watch out: Step numbers differ between books. Some split step 2 into two reactions through cis-aconitate, or count step 3’s CO₂ loss as its own step, and end up with 9 or 10. Learn the order of the molecules; it never changes.

Who has to memorize it

Check before you spend a week on it:

• AP Biology: no. College Board’s course description says memorizing the steps of glycolysis and the Krebs cycle, and the names of the intermediates, won’t be assessed. Know the location, the inputs and the outputs. The AP Biology study guide lists everything else the exam skips.
• MCAT: yes. The AAMC’s content outline lists the cycle’s reactions, substrates and products, its regulation and acetyl CoA production.
• College biology and biochemistry: usually yes. Ask whether your exam wants names only, or enzymes and structures too.

The mnemonic for the 8 intermediates

Citrate Is Krebs’ Starting Substrate For Making Oxaloacetate.

Each word gives one molecule, in order:

1. Citrate
2. Isocitrate
3. α-Ketoglutarate
4. Succinyl CoA
5. Succinate
6. Fumarate
7. Malate
8. Oxaloacetate

The two S’s: succinyl CoA, still holding its CoA, comes before plain succinate. The CoA comes off at step 5.

Watch out: The sentence reads as if citrate is used to make oxaloacetate. It’s the other way round: oxaloacetate is the partner acetyl CoA joins to make citrate, and the cycle rebuilds it at step 8.

Two patterns that do half the work

Pattern 1: follow the carbons. Acetyl CoA brings 2 carbons to oxaloacetate’s 4, so citrate has 6. Isocitrate is the same molecule rearranged, still 6. Then steps 3 and 4 each cut off one CO₂: 6 → 5 → 4. Everything after that has 4 carbons.

So the whole carbon sequence is 6, 6, 5, 4, 4, 4, 4, 4, and you never have to memorize where CO₂ comes off: it’s wherever the count drops.

Pattern 2: dehydrogenases make the carriers. Four enzymes in the cycle are dehydrogenases, and each one strips electrons onto a carrier:

That’s the 3 NADH and 1 FADH₂ in the totals. The one GTP or ATP comes from step 5, where succinyl-CoA synthetase uses the energy in succinyl CoA’s bond to its CoA.

Tip: Succinate dehydrogenase is the odd one out because it sits in the inner mitochondrial membrane. Its FADH₂ hands electrons straight to the electron transport chain, where the same enzyme is also called complex II.

The enzymes, without a second list

Most enzymes are named after the molecule they work on. Isocitrate dehydrogenase acts on isocitrate, α-ketoglutarate dehydrogenase on α-ketoglutarate, succinate dehydrogenase on succinate, fumarase on fumarate and malate dehydrogenase on malate. If you know the intermediates, you know 5 of the 8.

Learn the other 3 by heart:

• Citrate synthase is named for what it makes: citrate, at step 1.
• Aconitase turns citrate into isocitrate, through a molecule called cis-aconitate.
• Succinyl-CoA synthetase turns succinyl CoA into succinate and makes the GTP or ATP.

Mnemonic: Can An Iguana Keep Six Snacks For Me? Citrate synthase, Aconitase, Isocitrate dehydrogenase, α-Ketoglutarate dehydrogenase, Succinyl-CoA Synthetase, Succinate dehydrogenase, Fumarase, Malate dehydrogenase.

Regulation, for the MCAT and biochem

Three steps are irreversible, and they’re the ones the cell controls:

1. Step 1, citrate synthase: highly exergonic; slowed when ATP is plentiful.
2. Step 3, isocitrate dehydrogenase: slowed by ATP and NADH, sped up by ADP.
3. Step 4, α-ketoglutarate dehydrogenase: slowed by ATP, succinyl CoA and NADH.

The logic is one sentence: when the cell already has plenty of energy (ATP, NADH), the cycle slows; when it’s running low (ADP), it speeds up.

The mix-ups that cost points

• Succinyl CoA vs succinate: succinyl CoA comes first (step 4’s product); succinate is what’s left after step 5 removes the CoA and makes GTP.
• Citrate vs isocitrate: same 6 carbons, different arrangement. Aconitase only moves atoms around; nothing is released.
• Fumarate vs malate: fumarate gains water to become malate at step 7; malate then gives up NADH to become oxaloacetate.
• NADH count: 3 per turn. If you count 4, you’ve added the NADH from pyruvate oxidation, which happens before the cycle starts.
• ATP per turn: 1 GTP or ATP directly. Most of the ATP from respiration comes later, when the electron transport chain uses the NADH and FADH₂.
• GTP or ATP: both are right. Heart and skeletal muscle use the ATP-making form of the enzyme; the liver uses the GTP-making form.

A 7-day plan

Spreading the same study time over several days beats one long session for long-term recall (Cepeda et al., 2006; Dunlosky et al., 2013). About 15 minutes a day:

Quiz tomorrow? Do days 1 to 3 tonight, sleep, and run the deck once in the morning. You’ll keep the intermediates and the totals; the enzymes will be shakier.

The deck: every step, both directions

The 51 cards below cover the order (forward and backward), each molecule’s carbons, each step’s enzyme and products, the totals per turn and per glucose, and regulation. Pyruvate oxidation is in there too, because exams ask where the “extra” NADH and CO₂ come from.

If you’re also learning the building blocks the cycle connects to, how to memorize the amino acids covers all 20 with both codes.