Urea Cycle Flashcards
Overall rxn
NH3 + Asp + CO2 -> Urea + Fumarate
Which reactions take place in the mitochondria
Creation of Carbamoyl-P and combination of CP with OAA to create Citrulline
Other rxns in cytosol
What components create Carbamoyl-P?
NH3 + CO2 + Asp + 2 ATP
via Carbamoyl-P Synthetase 1
How is Citrulline created?
OAA combine with CP by Ornithine Transcarbamoylase
How is the urea cycle adaptive?
A high protein diet, or starvation, will cause the levels of urea cycle enzymes to go up
How is Carbamoyl-P synthetase 1 regulated?
1) Acetyl-Glutamate: increased levels of aa (eg. Glu) results in acetylation and upregulation of the Urea cycle
2) NH3 concentration
What follows Citrulline creation
Citrulline is combined with Aspartate to create Arginiosuccinate via Arginiosuccinate synthetase
ATP -> AMP + PPi
What follows creation of Arginiosuccinate?
Split into Arginine and Fumarate via Arginiosuccinase
What happens after creation of Fumarate and Arginine
Fumarate is recycled back through TCA to end up at OAA, which is then converted onto Asp
Arginine is split into Ornithine and Urea by arginine, Ornithine is then transported back into the mitochondria
How is OAA converted into Asp for entry into the Urea cycle
OAA combines with Glutamate to produce Aspartate and ⍺KG
⍺KG is recycled back to Glutamate by the conversion of amino acids to keto acids
How does Ammonia made in the muscle get to the liver for disposal
Amino acids get turned into keto acids, with the amino group being added to glutamate
This generates ⍺KG, which is then combined with Pyruvate to create Alanine
Alanine can travel in the blood (alanine cycle), so it goes to the liver, where it is combined with ⍺KG to produce Glutamate
The Glutamate can then be made into Asp via AST, or NH3 via GDH
Asp and NH3 then combine to make Urea
How does ammonia in most tissues get to the liver
It is combined with Glutamate via Glutamate Synthase and ATP to produce Glutamine
The Glutamine is then broken down to NH3 or Glutamate via Glutaminase in the liver
