Urea cycle and Cori cycle Flashcards
What distinguishes ornithine transcarbamylase deficiency from orotic aciduria?
- Enzyme deficient in orotic aciduria is UMP synthetase
- Orotic aciduria will not have hyperammonemia, as it involves pyrimidine synthesis, not urea cycle
Rate-limiting enzyme for urea cycle? Cofactor?
Carbamoyl phosphate synthetase I
N-acetylglutamate
Besides alanine, what else goes from muscle to liver during the Cori cycle?
Lactate
(byproduct of glycolysis in muscle, feeds into GNG in liver)
What distinguishes N-acetylglutamate deficiency from urea cycle enzyme deficiencies?
Hyperammonemia but normal urea cycle enzymes
(N-acetylglutamate is a cofactor for carbamoyl phosphate synthetase I, not an enzyme!)
Where does the urea cycle take place?
Mtiochondria and cytoplasm
î orotic acid
Î NH4
Decreased BUN
Ornithine transcarbamylase deficiency
What do ornithine transcarbamylase deficiency and orotic aciduria have in common?
Elevated levels of orotic acid
What is the purpose of the Cori cycle?
Shuttle nitrogens from muscle to liver for urea cycle
Most common urea cycle enzyme deficiency
Ornithine transcarbamylase deficiency
Describe the Cori cycle in muscle
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
What results from a deficiency in urea cycle enzymes?
Congential hyperammonemia
Increased [orotic acid] with megaloblastic anemia
Orotic aciduria
(But normal folate and B12)
Cerebral edema + blurred vision + slurring of speech + somnolence + vomiting + tremor
Hyperammonemia
(tremor = asterixis)
Mode of inheritance: ornithine transcarbamylase deficiency
X-linked recessive
(All other urea cycle enzyme deficiencies are AR)
What would you expect in the blood of a neonate with N-acetylglutamate deficiency?
Hyperammonemia with normal urea cycle enzymes
Increased [orotic acid] without hyperammonemia
Orotic aciduria
(No UMP synthetase = can’t convert orotic acid to UMP in pyrimidine synthesis pathway)
Rx for hyperammonemia
Lactulose - acidifies urine and traps NH4+
Benzoate and phenylbutyrate - bind a.a’s causing excretion
Where does the Cori cycle take place?
Skeletal muscle and liver
Describe the Cori cycle in the liver
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
In the Cori cycle, what is shuttled from muscle to liver? Liver to muscle?
Muscle to liver –> alanine (carrying NH3)
Liver to muscle –> glucose
Where do the two nitrogens in urea come from?
1 from NH3
1 from aspartate
How could one acquire hyperammonemia?
Liver disease
Increased [orotic acid] with hyperammonemia
Ornithine transcarbomylase deficiency