The ornithine cycle

The ornithine cycle (also called the urea cycle) is a series of reactions in liver cells that turns toxic ammonia into urea. Ammonia comes from breaking down excess amino acids. In the cycle, ammonia and carbon dioxide join onto a molecule called ornithine, which becomes citrulline, then arginine. Arginine is split to release urea, and ornithine is made again, ready to go round once more. Overall, two ammonia molecules and one carbon dioxide make one urea and one water.

Why the body makes urea

The body cannot store excess amino acids. Any that are not needed to make proteins are broken down in the liver. The amino group (NH₂) is removed and becomes ammonia, NH₃. Ammonia is very soluble and highly toxic: even small amounts in the blood are dangerous. The liver turns it straight into urea, which is much less toxic. Urea dissolves in the blood plasma, is carried to the kidneys, filtered out and excreted in urine.

OCR A Level Biology A includes the formation of urea from ammonia reacting with carbon dioxide as part of the ornithine cycle, among the roles of the liver, and says learners are not required to know the details of the cycle. The steps below go a little further, because they make the cycle easier to remember.

Step 1: deamination

Deamination removes the amino group from an amino acid. It makes ammonia and a keto acid:

The keto acid is not wasted. It can be respired to release energy, or turned into glucose or fat and stored. Only the nitrogen part has to be removed from the body.

Step 2: the ornithine cycle

1. Ornithine to citrulline: ammonia and carbon dioxide combine with ornithine, forming citrulline and releasing water.
2. Citrulline to arginine: a second ammonia combines with citrulline, forming arginine and releasing water.
3. Arginine to ornithine: water is added and arginine is split into urea and ornithine. The ornithine goes back to step 1.

Ornithine is used and then made again, so a small amount of it can process a lot of ammonia: it works like a carrier, not a raw material. The cycle also uses energy from ATP.

The overall equation

Check the balance: there are 2 nitrogen, 6 hydrogen, 1 carbon and 2 oxygen atoms on each side. Two waters are released when citrulline and arginine form, and one is used when arginine splits, which leaves one water overall.

Check your understanding.

Where the ornithine cycle fits in excretion

Excretion is removing the waste products of metabolism. Nitrogenous waste from amino acids is one of the main ones, along with carbon dioxide from respiration. The liver makes the urea; the kidneys remove it. In the kidney, urea is small enough to pass out of the blood in ultrafiltration, and much of it stays in the filtrate, so it ends up in urine. For how the blood reaches every organ, see the heart, and for the fluid that bathes cells, tissue fluid.

Explore how the body's systems work together, including digestion and homeostasis, in the Human Physiology course.

Exam questions with answers

Explain why excess amino acids are deaminated.

Amino acids cannot be stored. Deamination removes the nitrogen-containing amino group as ammonia, so the rest of the molecule, the keto acid, can be respired or stored as glucose or fat.

Explain why ammonia is converted to urea.

Ammonia is highly toxic and very soluble, so it must not build up in the blood. Urea is much less toxic, so it can be carried safely in the blood plasma to the kidneys and excreted.

Common mistakes

• Saying the kidneys make urea. The liver makes it; the kidneys excrete it.
• Saying urea is harmless. It is much less toxic than ammonia, but it still has to be excreted.
• Missing deamination. Amino acids are deaminated first; it is the ammonia that enters the cycle.
• Thinking ornithine is used up. It is regenerated every turn.
• Unbalanced overall equation. It is 2NH₃ + CO₂ → CO(NH₂)₂ + H₂O.

Practise with a short timed paper

Excretion and the liver are in the second year of A-level Biology. The daily A-level Biology: Year 2 paper is a short timed paper of 8 questions, with a new one every day.

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