Urea Cycle

Question 1

Where does urea get its components?

Answer 1

Nitrogen comes from aspartate and ammonia (NH4+)

Carbon comes from CO2

Question 2

What process leads to most of the NH4+ in the urine?

Answer 2

Deamidation

Question 3

What is removed in deamination? Which amino acids go through it?

Answer 3

Alpha-amino group is removed

Glutamate, glycine, serine, threonine, and histidine are removed

Question 4

Which amino acids undergo deamidation?

Answer 4

Glutamine and asparagine

Question 5

What is the main pathway of amino acid nitrogen removal? What occurs?

Answer 5

Transamination is the main pathway of amino acid nitrogen removal. Transfer of an amino group from an amino acid to an alpha-keto acid occurs

Question 6

How does transamination take place?

Answer 6

Transamination occurs using the enzyme transaminases such as aminotransferases. The coenzyme is pyridoxal phosphate (PLP) or vitamin B6 – pyridoxine

Question 7

What is used for diagnosing MI, ALT or AST?

Answer 7

ALT. It is more sensitive

Question 8

What is the purpose of transamination?

Answer 8

Transamination collects nitrogen on glutamate rather than release free ammonia

Question 9

Where does the urea cycle take place?

Answer 9

The urea cycle takes place in the liver

Question 10

Since other tissues also degrade amino acids, nitrogen is produced in those tissues. How is the nitrogen produced in those tissues transported to the liver?

Answer 10

They are transported by way of alanine or glutamine

Question 11

After urea is synthesized, what happens to it?

Answer 11

It is transported to the kidney and is excreted in urine (some leave by way of the intestine)

Question 12

What is the first step of the urea cycle?

What is the enzymes that catalyzes it?

What is its significance?

Answer 12

Carbamoyl phosphate synthesis

Carbamoyl phosphate synthase I

It is the rate-limiting, committed, irreversible step

Question 13

CPSI or N-acetylglutamate synthase deficiency leads to

Answer 13

Type I hyperammonemia

Question 14

What can high levels or arginine lead to?

Answer 14

Increased levels of N-acetyl-glutamine, which leads to the increased levels of CPSI activity, leading to the increase in urea production

High arginine can also lead to increased ornithine production and lead to an increase in urea production

Question 15

Deficiency in ornithine translocase causes this disease

Answer 15

hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome

Question 16

Deficiency in ornithine transcarbamoylase causes this disease

Answer 16

Type II hyperammonemia

Question 17

Deficiency of argininosuccinate synthetase causes this disease

Answer 17

Citrullinuria type I

Question 18

Deficiency of arginosuccinate lyase leads to this disease

Answer 18

Argininosuccinyl acidemia

Question 19

Arginase deficiency can cause this disease

Answer 19

Argininemia

Question 20

What is the treatment for argininosuccinate lyase deficiency?

Answer 20

Argenine – it generates more ornithine for the urea cycle to continue

Question 21

Treatment for type I and II hyperammonemia

Answer 21

Citrulline — it captures aspartate, so at least one nitrogen can be excreted

Question 22

What is the first step in urea synthesis?

What catalyzes the reaction?

What is its allosteric activator?

Answer 22

Carbamoyl phosphate synthesis

Catalyzed by carbamoyl phosphate synthase I (CPSI). Rate-limiting, committed step, which requires 2 ATPs

Allosterically activated by N-acetyl-glutamate

Question 23

What is the second step in the urea cycle?

What catalyzes the reaction and where does it take place?

What transports the reactants to the site of the reaction?

Answer 23

Citrulline synthesis

Catalyzed by ornithine transcarbomylase, which takes place in the mitochondria

Ornithine is transported into the mitochondria from the cytosol by ornithine translocase

Question 24

What is the third step in the urea cycle?

What catalyzes the reaction and what is required?

What is its cofactor and how is it produced?

Answer 24

Argininosuccinate synthesis

Catalyzed by argininosuccinate synthetase, which takes place in the cytosol and requires 1 ATP molecule

Aspartate is produced by transamination of OAA, aspartate nitrogen will incorporate into urea

Question 25

What is the fourth step in the urea cycle?

Where does this step occur?

What catalyzes this reaction?

What is released in the process and what happens to it?

Answer 25

Arginine synthesis

Takes place in the cytosol

Argininosuccinate lyase, which

The released fumarate can enter the TCA cycle and regenerate OAA and then aspartate

Question 26

What is the fifth (last) step in the urea cycle?

What catalyzes this reaction?

Where does it take place?

Answer 26

Cleavage of arginine into urea and ornithine

Catalyzed by arginase.

This takes place in the cytosol.

Ornithine moves back to the mitochondria and can be recycled