7A-Urea Cycle

Question 1

What are the 2 sources of ammonia for the urea cycle?

Answer 1

Ammonium (NH4) and Asp

Question 2

What is produced when Asp donates its nitrogen to alpha-ketogluterate?

Answer 2

Asp + a-KG –> OAA + Glu

Question 3

What 2 amino acids are primarily released into the bloodstream from muscle during the fasted state?

Answer 3

Ala and Gln

Question 4

What does Gln from proteolysis serve to do during the fasted state?

Answer 4

It travels to the blood, dumps its extra NH3 to the kidney to be excreted, this converts it to Ala, and then heads to the liver to be used in gluconeogenesis

Question 5

How do nitrogens remove their amino acid?

Answer 5

amino acids donate their amine group to alpha ketoglutarate, and make glutamate, using PLP as a cofactor

Question 6

What is PLP derived from?

Answer 6

pyridoxine (Vitamin B6)

Question 7

What are some symptoms of PLP deficiency?

Answer 7

include dermatitis, microcytic, hypochromic anemia (due to inability to make heme from glycine), weakness, irritability, and sometimes convulsions. Sometimes Xanthurenic acid and other compounds that were not successfully metabolized appear in the urine

Question 8

Why cant ammonium cross the cell membrane but ammonia can?

Answer 8

Ammonium ion is no longer hydrophobic enough to cross the membrane due to its charged status. Ammonia can cross due to it being less polar than ammonium.

Question 9

Why isn’t ammonia absorbed by the intestine not immediately toxic?

Answer 9

Ammonia is absorbed by the intestine via the portal system, which actually contains a lot more ammonia than systemic blood. The portal system, being separate from systemic blood flow, carries ammonia to the Liver, where it is fixed to glutamate and glutamine

Question 10

When plasma Ala arrives at the liver, what happens to it?

Answer 10

it is transaminated to pyruvate for gluconeogenesis, and the nitrogen sent to the urea cycle

Question 11

Why is glutamine important in the blood?

Answer 11

Glutamine is important as it picks up any escaping ammonia, so there isn’t free ammonia floating around in the bloodstream. Glutamine synthetase makes glutamine from glutamate and ATP. Glutamine then can move around to different locations of the body, such as the kidney or liver, and then the glutaminase enzyme will break glutamine down to glutamate to release the ammonia, which is then able to be sent to the urea cycle.

Question 12

What is the role of glutamate dehydrogenase for the urea cycle?

Answer 12

After a Glu is formed from a-KG, GDH converts it back to a-KG + a NH4 group, which the ammonium is brought to the urea cycle

Question 13

How can Glu undergo a transamination to form Asp for the urea cycle?

Answer 13

Glu + OAA –transamination–> a-KG + Asp

Question 14

What occurs during the 1st step of the urea cycle, when HCO3 reacts with NH4?

Answer 14

HCO3 reacts with NH4 using (2ATP –> 2ADP+ 2Pi) –CPS1–> carbamoyl phosphate

Question 15

What occurs during the 2nd step of the urea cycle, when carbamoyl phosphate reacts with ornithine?

Answer 15

Carbamoyl phosphate + ornithine –OTC–> Pi + citrulline

Question 16

What happens when citrulline is formed?

Answer 16

It is exported from the mitochondria

Question 17

What occurs during the 3rd step of the urea cycle when citrulline reacts with Asp?

Answer 17

Citrulline + Asp using (ATP –> AMP + PPi) –> arginosuccinate

Question 18

What occurs during the 4th step of the urea cycle with arginosuccinate?

Answer 18

Arginosuccinate –> Fumerate + Arg

Question 19

What occurs during the 5th and final step of the urea cycle with Arg?

Answer 19

Arg –> ornithine + UREA

Question 20

How does N-acetylglutamate activate the urea cycle?

Answer 20

N-acetylglutamate (NAG) is formed to activate the first enzyme in the urea cycle, carbamoyl phosphate synthetase I (CPSI), which makes carbamoyl phosphate. NAG is created from acetyl CoA and glutamate, and this reaction is positively activated by arginine.