Urea cycle Flashcards
What is urea?
A non toxic secretory form of ammonia produced from the byproducts of amino acid metabolism.
NH4+ > urea cycle > H2N-CO-NH2 (each urea cycle excretes two ammonia ions)
Uric acid is another form used to dispose of nitrogenous waste.
How does the first ammonium ion enter the urea cycle?
Deamination of glutamate (only have to remember glutamate for the purpose of exams but there are others) within the mitochondrial matrix produces ammonia which then combines with bicarbonate to form carbamoyl phosphate via carbomyl phosphate synthetase.
Carbamoyl phosphate in turn enters the urea cycle via ornithine trans carbomylase.
How does the second ammonium ion enter the urea cycle?
Glutamate can undergo transamination and donate its amino group to oxaloacetate giving aspartate via aspartate aminotransferase and α-ketoglutarate.
Aspartate can enter the urea cycle.
What is the overall equation for the urea cycle?
CO2 + NH4+ + 3ATP + aspartate + 2H2O -> urea + 2ADP + Pi + AMP + PPi + fumarate
Energy demanding process
What causes urea cycle disorders?
Dysfunctional enzymes.
What is glutamines role in the urea cycle?
Glutamine can be used by any tissue to remove amino groups and it is transported to the kidneys to feed into the urea cycle.
How is ammonia transported to the liver?
In an extrahepatic tissue ammonia is used to form glutamate via glutamate dehydrogenase from α-ketolgutarate. Glutamate is then converted to glutamine via glutamine synthetase which can then enter the blood and be transported into the liver. Once in the liver glutaminase breaks glutamine down into glutamate and ammonia -> ammonia enters the urea cycle.
What is the role of the liver in the urea cycle?
The liver is a key site for amino acid catabolism to produce carbon skeletons for fuel. The ammonia byproduct of amino acid catabolism enter the urea cycle. The key intermediate of the urea cycle, citrulline, is produced in the liver.
What is the kidneys role in the urea cycle?
The kidneys excrete the urea produced by the liver. In a process complementary to the livers function, the kidneys metabolises glutamine and ammonia to excrete nitrogen. The kidneys are a major site of arginine synthesis from citrulline produced in the liver
