Urea Cycle Flashcards
Where does urea get its components?
Nitrogen comes from aspartate and ammonia (NH4+)
Carbon comes from CO2
What process leads to most of the NH4+ in the urine?
Deamidation
What is removed in deamination? Which amino acids go through it?
Alpha-amino group is removed
Glutamate, glycine, serine, threonine, and histidine are removed
Which amino acids undergo deamidation?
Glutamine and asparagine
What is the main pathway of amino acid nitrogen removal? What occurs?
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
How does transamination take place?
Transamination occurs using the enzyme transaminases such as aminotransferases. The coenzyme is pyridoxal phosphate (PLP) or vitamin B6 – pyridoxine
What is used for diagnosing MI, ALT or AST?
ALT. It is more sensitive
What is the purpose of transamination?
Transamination collects nitrogen on glutamate rather than release free ammonia
Where does the urea cycle take place?
The urea cycle takes place in the liver
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?
They are transported by way of alanine or glutamine
After urea is synthesized, what happens to it?
It is transported to the kidney and is excreted in urine (some leave by way of the intestine)
What is the first step of the urea cycle?
What is the enzymes that catalyzes it?
What is its significance?
Carbamoyl phosphate synthesis
Carbamoyl phosphate synthase I
It is the rate-limiting, committed, irreversible step
CPSI or N-acetylglutamate synthase deficiency leads to
Type I hyperammonemia
What can high levels or arginine lead to?
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
Deficiency in ornithine translocase causes this disease
hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome
Deficiency in ornithine transcarbamoylase causes this disease
Type II hyperammonemia
Deficiency of argininosuccinate synthetase causes this disease
Citrullinuria type I
Deficiency of arginosuccinate lyase leads to this disease
Argininosuccinyl acidemia
Arginase deficiency can cause this disease
Argininemia
What is the treatment for argininosuccinate lyase deficiency?
Argenine – it generates more ornithine for the urea cycle to continue
Treatment for type I and II hyperammonemia
Citrulline — it captures aspartate, so at least one nitrogen can be excreted
What is the first step in urea synthesis?
What catalyzes the reaction?
What is its allosteric activator?
Carbamoyl phosphate synthesis
Catalyzed by carbamoyl phosphate synthase I (CPSI). Rate-limiting, committed step, which requires 2 ATPs
Allosterically activated by N-acetyl-glutamate
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?
Citrulline synthesis
Catalyzed by ornithine transcarbomylase, which takes place in the mitochondria
Ornithine is transported into the mitochondria from the cytosol by ornithine translocase
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?
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
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?
Arginine synthesis
Takes place in the cytosol
Argininosuccinate lyase, which
The released fumarate can enter the TCA cycle and regenerate OAA and then aspartate
What is the fifth (last) step in the urea cycle?
What catalyzes this reaction?
Where does it take place?
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
