Urea Cycle

Question 1

In humans what is most excess nitrogen excreted as?

Answer 1

urea

Question 2

Besides urea, what are other nitrogen containing excretory products?

Answer 2

NH4, creatinine, urobilins, uric acid

Question 3

Where is urea synthesized?

Answer 3

liver

Question 4

Which amino acids transfer ammonia in a non-toxic form to the liver?

Answer 4

alanine, glutamate, and glutamine

Question 5

Which amino acids (and others) result in ammonia production directly?

Answer 5

serine, threonine, glycine, and purines

Question 6

The ammonia produced by the tissues is a substrate for what?

Answer 6

glutamate dehydrogenase or glutamine synthase

Question 7

What is the order of the urea cycle?

Answer 7

carbamoyl phosphate-> ornithine transcarbamoylase-> cirtulline-> argininocuccinate synthase–> arginainosuccinate lyase–> arginase

Question 8

Ornithine trascarbamoylase (OTC)

Answer 8

mitochondria

ornithine + carbamoyl phosphate = citrulline

Question 9

how is citrulline transported out of the mitochondria?

Answer 9

citrulliine/ornithine antiport

Question 10

argininosuccinate sythase

Answer 10

cytosol
requires ATP hydrolysis to AMP +PPi
citrulline + aspartate = argininosuccinate

Question 11

argininosuccinate lyase

Answer 11

cytosol

argininosuccinate = arginine + fumarate

Question 12

Describe the formation of carbamoyl phosphate

Answer 12

carbamoyl phosphate synthase 1(CPS1) (stimulated by N-acetylglutamate)
w/in mitochondria
requires 2 ATP per molecule
N-acetylglutamate synthase stimulated by arginine

Question 13

Arginase

Answer 13

cytosol
arginine = ornithine + urea
(regenerates ornithine)

Question 14

What is the hallmark feature of any of the urea cycle deficiencies except for arginase?

Answer 14

elevated ammonia in the blood (hyperammonemia) often accompanied by elevated glutamine

Question 15

Arginase deficiency

Answer 15

hyperarginemia
elevation of serum arginine
insidious onset of spasticity after several months or years
progressive mental retardation, seizures
treatment of low protein diet devoid of arginine

Question 16

What is arginase deficiency commonly mistaken as?

Answer 16

cerebral palsy

Question 17

Hyperammonemia

Answer 17

sx in early childhood
frequent vomiting, poor appetite, protein aversion
somnolence, inability to maintain normal body temp and poor feeding
lethargy, coma

Question 18

Deficiency of carbamoyl synthase 1 or N-acetylglutamate synthase

Answer 18

elevated ammonia and glutamine

Question 19

Ornithine transcarbamoylase deficiency

Answer 19

elevated ammonia,glutamine, urinary orotic acid
excess carbamoyl phosphate leaks into the cytosol where it is used for the synthesis of orotic acid a precursor of pyrimidines

Question 20

argininosuccinate synthase deficiency

Answer 20

elevated ammonia, glutamine, and citrulline

Question 21

deficiency of argininosuccinate lyase

Answer 21

elevated ammonia, glutamine, citrulline, argininosuccinate

Question 22

What is the treatment for hyperammonemia?

Answer 22

low protein diet
provide an alternative method for nitrogen removal (benzoic acid and/or phenyl butyric acid)
supplement with arginine (allows the reformation of ornithine via arginase)
carglumic acid (will stimulate CPS1)