Nitrogen Metabolism and Urea Cycle- Brar

Question 1

What is the overall stoichiometry of the urea cycle?

Answer 1

4 high-energy phosphate bonds consumed (2 ATPs in first step, 2 Pi bonds from breaking ATP in third step into AMP and pyrophosphate)
Therefore, synthesis of Urea is irreversible (large, negative ΔG)

Question 2

How is ammonia (NH3) formed? Where does this rxn take place? This is the source of ammonia for urea synthesis.

Answer 2

Glutamate + NAD+ → α-ketoglutarate + NADH + NH3 (In liver and kidney)

Question 3

How is ammonia transported?

Answer 3

glutamate + NH3 → glutamine + ADP + Pi
-Glutamine is transported from liver to other tissues via blood, ammonia is NOT stored, glutamine rxn is important for ammonia removal in the brain

Question 4

What conditions are associated with a positive nitrogen balance (nitrogen consumed > nitrogen excreted)?

Answer 4

1. Childhood
2. Pregnancy
3. Muscle building
4. Healing

Question 5

What conditions are associated with a negative nitrogen balance (nitrogen excreted > nitrogen consumed)?

Answer 5

1. Protein malnutrition
2. Deficiency of essential amino acids
3. Stress (fever, inflammation, surgery etc…)

Question 6

What is the major site of urea synthesis?

Answer 6

Liver (has all necessary enzymes), other tissues can only make arginine or NO

Question 7

Where do the 2 nitrogens in urea come from?

Answer 7

Aspartate and ammonia