Biochem 41 | Urea Cycle

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Explain the Urea Cycle (step-by-step)

The urea cycle is a process in the liver that helps remove excess nitrogen from the body by converting toxic ammonia into urea, which is then excreted in the urine.

1. Ammonia (NH3), which is toxic, is produced when proteins are broken down.

2. In the mitochondria of liver cells, ammonia combines with CO2 and ATP to form carbamoyl phosphate (with the help of an enzyme called CPS I).

3. Carbamoyl phosphate joins with ornithine to form citrulline. Citrulline is then transported out of the mitochondria into the cytosol (the cell fluid).

4. In the cytosol, citrulline combines with aspartate (another amino acid) to form argininosuccinate.

5. Argininosuccinate is split into arginine and fumarate.

6. Arginine is then broken down into urea (which is excreted) and ornithine, which goes back into the mitochondria to start the cycle again

What are the sources of nitrogen in the urea cycle?

• Ammonia (NH3), which is produced by the breakdown of amino acids.

• Aspartate, which donates the second nitrogen group during the urea cycle.

What is positive versus negative nitrogen balance?

• Positive nitrogen balance: Nitrogen intake is greater than nitrogen excretion, usually during growth, pregnancy, or tissue repair.

• Negative nitrogen balance: Nitrogen excretion is greater than intake, often due to injury, illness, or malnutrition

How does nitrogen balance affect blood urea nitrogen? Is BUN high or low in positive nitrogen balance?

In positive nitrogen balance, BUN is usually low because less nitrogen is being excreted. In negative nitrogen balance, BUN is high due to increased nitrogen excretion

What are the two main sources of amino acids for the body?

Dietary protein and cellular protein degradation​

How do the glutamine and glucose-alanine cycles help remove excess nitrogen? What does the muscle get in return for sending alanine to the liver?

Both cycles transport nitrogen to the liver. In the glucose-alanine cycle, the muscle sends alanine to the liver, and in return, the liver provides glucose to the muscle​

What are the sources of the two nitrogen groups in the urea molecule?

The two nitrogen groups in urea come from ammonia (free NH3) and aspartate

What is the relationship between ammonia (NH3) and ammonium ion (NH4+)? Which form dominates at body pH, and why?

At body pH (7.2–7.4), ammonium ion (NH4+) dominates because the equilibrium strongly favors NH4+ due to its high pKa (9.3)​

Why does BUN change under different metabolic conditions, such as high-glucose meals or fasting?

BUN is lower after a high-glucose meal because less protein is being broken down. During fasting, BUN increases as more amino acids are degraded for energy, especially during prolonged fasting when proteins are used for gluconeogenesis

Explain the glucose-alanine cycle step by step

1. When muscles break down amino acids for energy, they generate nitrogen waste. The nitrogen combines with pyruvate (from glucose breakdown) to form alanine.

2. Alanine is sent through the bloodstream to the liver.

3. The liver removes nitrogen from alanine and converts it to urea for excretion. The leftover part of alanine is turned back into glucose, which is sent back to the muscles for energy.

Basically, the Glucose-Alanine Cycle allows muscles to get rid of nitrogen safely and recycle glucose for energy.

Explain the glutamine cycle step by step

1. When amino acids are broken down, nitrogen waste is combined with glutamate to form glutamine.

2. Glutamine travels to the liver or kidneys, which can safely dispose of the nitrogen.

3. The nitrogen is removed from glutamine and processed (usually turned into urea in the liver) for excretion.

Basically, the Glutamine Cycle moves nitrogen safely to the liver and kidneys, where it can be removed, helping prevent toxic buildup in tissues.