urea cycle

Question 1

what is the treatment for hyperammonemia?

Answer 1

limit protein intake
benzoate or phenoxybutyrate
lactulose
rifaximin

Question 2

pt hepatic encephalopathy is treated with a drug that binds amino acids and promotes their excretion. What was the drug?

Answer 2

benzoate or phenoxybutyrate

Question 3

pt hepatic encephalopathy is treated with a drug that acidifies the gut and converts NH3 to NH4+. What was the drug?

Answer 3

lactulose

Question 4

pt hepatic encephalopathy is treated with a drug that reduces gut flora thereby preventing ammonia absorption. What was the drug?

Answer 4

rifaximin

Question 5

what is the hallmark symptom of hepatic encephalopathy?

Answer 5

asterixis (flapping hand tremor)

other symptoms:
vomiting
lethargy
cerebral edema
slurred speach
blurred vision

Question 6

what is the first and rate limiting enzymatic reaction involved in eliminating ammonia?

Where does it take place?

What is the co-factor?

Answer 6

conversion of CO2 and ammonia to carbamoyl phosphate

Enzyme:carbamoyl phosphate synthetase 1
Location: mitochondria
Co-factor:N-acetyl-glutamate (requires 2ATP)

Question 7

pt presents with increased orotic acid in blood and urine, decreased BUN and hyperamonemia. What enzyme deficiency caused this? Where does the deficient Rxn normally take place?

Answer 7

X-linked deficiency of ornithine transcarbamolase (transfers carbamoyl moiety to ornithine to form citruline in the mitochrondria, citruline is then normally transported to cytoplasm)

excess carbamoyl phosphate builds up and is then converted to orotic acid (a pyrimidine synthesis intermediate)

Question 8

pt presents with increased orotic acid in blood and urine. How can ornathine transcarbamolase deficiency be distinguished from orotic aciduria (deficiency in de novo pyrimidine synthesis pathway)?

Answer 8

ornathine transcarbamolase deficiency has hyperammonemia (can’t be eliminated due to defective urea cycle) whereas orotic aciduria (deficiency of UMP synthase) has megaloblastic anemia (not responsive to B12 or folate but improves with uricil supplimentation).

PRPP + Orotic acid combine to form UMP via UMP synthetase