Nitrogen and urea cycle

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Nitrogen and urea cycle



Nitrogen and urea cycle


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Nitrogen and urea cycle

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USMLE® Step 1 style questions USMLE

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Biochemistry researchers are studying the metabolic pathway involved in the removal of toxic ammonia molecules. Which of the following reactions of these metabolic pathways occurs in the mitochondria?  

External References

First Aid








Adenosine triphosphate (ATP)

in urea cycle p. 80

Amino acids

urea cycle p. 80


urea cycle p. 80

Metabolism p. 70-92

urea cycle p. 80


urea cycle p. 80

Urea cycle p. 80

diagram p. 72

metabolic site p. 70

ornithine transcarbamylase deficiency and p. 81

rate-determining enzyme for p. 71


Content Reviewers

The human body generates a lot of waste products, and fortunately, our kidney is capable of getting rid of most of them.

However, there is one arch nemesis that the kidney can’t deal with on its own. So, the liver comes to the rescue. The villain is ammonia.

Ammonia is the major toxin that results from the metabolism of amino acids.

Amino acids are made of a nitrogen group, a carbon skeleton, and a side chain that is unique to each amino acid.

When amino acids are metabolized, the nitrogen is formed into ammonia, and ammonia is toxic to the cells.

So the ammonia is shuttle over to the liver and sent through the urea cycle, which is a series of enzymatic reactions that convert ammonia into urea.

The urea cycle takes place within the mitochondria, so that it doesn’t affect proteins and organelles in our cytoplasm.

Urea can then easily be dealt with by the kidney.

It’s a bit like how a mama bird might mash up a worm so that it’s easier for a baby bird to digest.

In this case the liver is the mama bird, and the kidney is the baby bird.

Alright, so first, ammonia needs to get to the liver.

And it has to be done carefully because it’s toxic.

So, much like a prisoner, it needs to be carried in the circulation by a police officer, to its prison, which is the liver mitochondria.

There are two ways this can happen. The first way is used throughout by cells throughout the body.

The enzyme glutamine synthetase adds ammonia to the amino acid glutamate forming glutamine.

Glutamine can move into the blood, and essentially transport ammonia around the block, until it gets to a liver cell.

Once inside the mitochondria of a liver cell, an enzyme called glutaminase cleaves glutamine back into glutamate and ammonia, and the ammonia can then enter the urea cycle.

The second way to move ammonia around is done mostly by skeletal muscle cells.

In skeletal muscle cells, the enzyme glutamate dehydrogenase incorporates ammonia into the molecule alpha-ketoglutarate and turns it into glutamate.

But unlike glutamine, glutamate can’t leave the cell on its own.

It needs to somehow give its ammonia to an amino acid that can leave the cell, and that’s alanine.

So, the enzyme alanine transaminase, or ALT, converts glutamate and pyruvate into alpha-ketoglutarate and alanine.

And alanine then moves into the blood, and ends up transporting ammonia to a liver cell, and once there it undergoes the reverse of the previous reactions.


The nitrogen cycle is the process by which nitrogen is converted between its various chemical forms. One important aspect of the nitrogen cycle is the urea cycle, which involves biochemical reactions that produce urea from ammonia. The urea cycle takes place primarily in the liver, and to a lesser extent in the kidney. Its main role is to convert excess nitrogen in the body into urea, which is then excreted in the urine.


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