urea cycle

Question 1

where does urea cycle take place? (tissue + organelle)

Answer 1

• primarily in liver
• mitochondria & cytosol

Question 2

what is the purpose of the urea cycle?

Answer 2

eliminate NH3 from the body by converting it to urea

Question 3

what is the structure of urea?

Answer 3

NH2–C=O–NH2

Question 4

where are urea’s C and N atoms derived from?

Answer 4

C: CO2
N: ammonia (NH3), aspartate

Question 5

which enzymes of urea cycle are found in the mitochondria? (2)

Answer 5

1. CP synthase 1
2. OTC

Question 6

which enzymes of urea cycle are found in the cytosol? (3)

Answer 6

1. ASS
2. ASL
3. Arginase

Question 7

true/false: the same transport protein carries ornithine & citrulline across inner mitochondrial membrane?

Answer 7

true

Question 8

how is the urea cycle regulated? (4)

Answer 8

1. Compartmentalization
2. Transcriptional and Translational Control (increase enzymes to upregulate urea cycle)
3. Feed-Forward Regulation
4. Allosteric Control

Question 9

what is the rate limiting enzyme of the urea cycle?

Answer 9

CP synthase 1

Question 10

what is the substrate, and allosteric activator for CP synthase 1?

Answer 10

substrate: NH3
activator: N-acetylglutamate

Question 11

how is N-acetylglutamate produced?

Answer 11

• Glu→ N-acetylglutamate
• allosterically controlled manner too: acetylglutamate synthase/N-acetyl-transferase (upregulated by Arg)
• increase Arg→ increase acetylglutamate synthase→ increase N-acetylglutamate→ activate CPS1→ increase carbamoyl phosphate

Question 12

what is the overall equation of urea synthesis?

Answer 12

NH4+ + HCO3- + Aspartate→ Urea + Fumarate + H+

3ATP→ 2ADP + AMP + 2Pi + PPi

Question 13

how is urea cycle and TCA cycle linked?

Answer 13

fumarate produced from urea cycle→ enters TCA cycle→ malate→ oxaloacetate→ re-enters urea cycle via conversion by aspartate transferase→ aspartate

Question 14

what disease causes defect in carbamoyl phosphate synthethase 1 (CPS1)?

Answer 14

hyperammonemia 1

Question 15

what disease causes defect in ornithine transcarbamoylase (OTC)?

Answer 15

hyperammonemia 2

Question 16

what disease causes defect in argininosuccinate synthetase (ASS)?

Answer 16

citrullinemia

Question 17

what disease causes defect in argininosuccinate lyase? (ASL)

Answer 17

argininosuccinic aciduria

Question 18

what disease causes defect in arginase?

Answer 18

argininemia

Question 19

how does ammonia get eliminated? (7)

Answer 19

assimilation (incorporated into organic compounds)
1. by glutamine synthetase (glutamate→ glutamine)
2. by glutamate dehydrogenase (a-KG→glutamate)
3. by carbamoyl phosphatate synthetase (CPS1)

excretion:
4. as NH4+ ions
5. as urea
6. as creatinine
7. as uric acid