Urea cycle and Cori cycle

Question 1

What distinguishes ornithine transcarbamylase deficiency from orotic aciduria?

Answer 1

1. Enzyme deficient in orotic aciduria is UMP synthetase
2. Orotic aciduria will not have hyperammonemia, as it involves pyrimidine synthesis, not urea cycle

Question 2

Rate-limiting enzyme for urea cycle? Cofactor?

Answer 2

Carbamoyl phosphate synthetase I

N-acetylglutamate

Question 3

Besides alanine, what else goes from muscle to liver during the Cori cycle?

Answer 3

Lactate

(byproduct of glycolysis in muscle, feeds into GNG in liver)

Question 3

What distinguishes N-acetylglutamate deficiency from urea cycle enzyme deficiencies?

Answer 3

Hyperammonemia but normal urea cycle enzymes

(N-acetylglutamate is a cofactor for carbamoyl phosphate synthetase I, not an enzyme!)

Question 4

Where does the urea cycle take place?

Answer 4

Mtiochondria and cytoplasm

Question 4

î orotic acid

Î NH₄

Decreased BUN

Answer 4

Ornithine transcarbamylase deficiency

Question 5

What do ornithine transcarbamylase deficiency and orotic aciduria have in common?

Answer 5

Elevated levels of orotic acid

Question 6

What is the purpose of the Cori cycle?

Answer 6

Shuttle nitrogens from muscle to liver for urea cycle

Question 6

Most common urea cycle enzyme deficiency

Answer 6

Ornithine transcarbamylase deficiency

Question 9

Describe the Cori cycle in muscle

Answer 9

NH₃ transfered to alpha-KG –> forms glutamate (NH₃) and alpha-ketoacids –> glutmate transfers NH₃ to pyruvate –> forms alanine and alpha-ketoglutarate –> alanine goes to liver

Pyruvate comes from glycolysis via the glucose from the liver

Question 11

What results from a deficiency in urea cycle enzymes?

Answer 11

Congential hyperammonemia

Question 11

Increased [orotic acid] with megaloblastic anemia

Answer 11

Orotic aciduria

(But normal folate and B12)

Question 12

Cerebral edema + blurred vision + slurring of speech + somnolence + vomiting + tremor

Answer 12

Hyperammonemia

(tremor = asterixis)

Question 12

Mode of inheritance: ornithine transcarbamylase deficiency

Answer 12

X-linked recessive

(All other urea cycle enzyme deficiencies are AR)

Question 13

What would you expect in the blood of a neonate with N-acetylglutamate deficiency?

Answer 13

Hyperammonemia with normal urea cycle enzymes

Question 15

Increased [orotic acid] without hyperammonemia

Answer 15

Orotic aciduria

(No UMP synthetase = can’t convert orotic acid to UMP in pyrimidine synthesis pathway)

Question 16

Rx for hyperammonemia

Answer 16

Lactulose - acidifies urine and traps NH₄⁺

Benzoate and phenylbutyrate - bind a.a’s causing excretion

Question 17

Where does the Cori cycle take place?

Answer 17

Skeletal muscle and liver

Question 18

Describe the Cori cycle in the liver

Answer 18

Alanine from muscle gives NH₃ to alpha-ketoglutarate –> generates pyruvate and glutamate (NH₃) –> glutamate goes to urea cycle and pyruvate goes to GNG to form glucose for muscle

Question 20

In the Cori cycle, what is shuttled from muscle to liver? Liver to muscle?

Answer 20

Muscle to liver –> alanine (carrying NH₃)

Liver to muscle –> glucose

Question 21

Where do the two nitrogens in urea come from?

Answer 21

1 from NH₃

1 from aspartate

Question 22

How could one acquire hyperammonemia?

Answer 22

Liver disease

Question 23

Increased [orotic acid] with hyperammonemia

Answer 23

Ornithine transcarbomylase deficiency