Script

As ammonium ions and aspartate ions are produced through deamination and transamination.
These two ions will be processed further in the urea cycle to produce urea, which is found in
urine, a waste product from our body.

Structure of urea:
The molecular formula for urea is CH4N2O. This compound is made up of a carbonyl (C=O)
group attached to two nitrogen groups (NH2).
Urea is very soluble in water, to be exact, 1ml of water could dissolve 1g of urea in its pure
state. It is odorless and colorless and has a very salty taste. Take note that urea does not
contribute to any physical appearance of urine.
There are three amino acids involved in the process,
Arginine, Ornithine, and Citrulline

For the formation of Carbamoyl phosphate, the ammonium ion product from oxidative
deamination reaction will be converted to carbamoyl phosphate with carbon dioxide (from the
Kreb’s cycle), water, and 2 ATP molecules to perform carbamoyl phosphate. Now, we have the
carbamoyl phosphate + 2ADP molecules + inorganic phosphate + 3H+ ions.

(Take note that carbamoyl phosphate contains high-energy bonds because it uses ATP
molecules to form.)

Steps of Urea Cycle

(There are four steps in the Urea Cycle. But before we tackle these steps, take note that the
urea cycle occurs partially in the mitochondrial matrix and partially in the cytosol. Also,
Ornithine and Citrulline must be transported through the inner mitochondrial membrane,
this is because we will need the enzyme from Ornithine (ornithine transcarbamoylase) to form
Citrulline.)

Step 1: Carbamoyl group transfer

As we have said earlier, carbamoyl phosphate will enter the cycle and will serve as one of
the fuels for the urea cycle. As ornithine will accept carbamoyl phosphate, allowing OTC
enzyme (ornithine transcarbamoylase) to form Citrulline with a release of Pi, an inorganic
phosphate.
Take note of the first step, (the first of the two nitrogen atoms of urea and its carbon atom, have
been formed, because of this transfer.)

Step 2: Citrulline aspartate condensation

This step will occur after citrulline from step 1 is transported into the cytosol. A quick
reminder, that the remaining steps will occur inside the cytosol. Only step 1 occurs inside the
mitochondrial matrix.
In step 2, Citrulline and the aspartate molecule, from the glutamate
transamination, will now serve as a fuel for condensation. Thus, the condensation
of citrulline and aspartate for the production of argininosuccinate is hereby
catalyzed by the enzyme argininosuccinate synthase.
This reaction is driven by the expenditure of ATP. In argininosuccinate formation, an oxygen
atom is “lost”; the reactants contain seven oxygen atoms, and the product contains six oxygen
atoms. This is because the reaction is actually a two-step process involving a citrullyl–AMP
intermediate (which reacts with an amino group from aspartate to produce argininosuccinate).
When the AMP is released, the “lost” oxygen atom becomes part of the AMP structure. Mainly
because this reaction introduces the second of the two nitrogen atoms that will be part of the
end-product of urea. One nitrogen atom is from the carbamoyl phosphate, and the other one is
from the aspartate which results from this step.

Step 3: Argininosuccinate cleavage

The 3rd step is when the enzyme argininosuccinate lyase catalyzes the cleavage of
argininosuccinate into arginine (a standard amino acid) and fumarate (a citric acid intermediate).

As we can see from the reaction, the argininosuccinate is broken down into arginine and
fumarate through cleavage, which is the splitting of chemical bonds. By the way, the presence
of fumarate in this cycle would be tackled later.

Step 4: Urea from arginine hydrolysis

For the last step, it would be the hydrolysis of arginine, forming the starting material of this
cycle, ornithine. The enzyme involved in this step is arginase.

The last step forms Urea and Ornithine. The water from urea comes from the hydrolysis
reaction. After this reaction, Ornithine is transported from cytosol to the mitochondrial matrix to
start the cycle again.

Now let us move on for our practice questions,

I will give 15-30 seconds for you to answer based on the difficulty of my questions

For the first question, what are the fuels for the urea cycle?
Carbamoyl Phosphate and Aspartate

Second question, what step in the urea cycle is the carbamoyl transfer?
Step 1

Third, What intermediate is fumarate?

A citric acid intermediate

Last question, where does step 2, 3, 4 takes place?

Is the cytosol