Lecture 17 Urea Cycle and Asp-Arg Shunt Flashcards
Excess amino acids can’t be stored, but what happens to the carbon skeletons after deamination/transamination?
They get mainly stored as fat
What are the 5 enzymes involved in the urea cycle? Which one is not directly in the cycle but rather prepares for the cycle to begin?
- Ornithine transcarbamoylase
- Arginiosuccinate synthetase
- Arginiosuccinase
- Arginase
- Carbamoylphosphate synthetase prepares for the cycel
Where is carbamoylphosphate found in the cell?
In an organelle. NOT cytosol
What is the overall reaction of the urea cycle? Where does this cycle occur?
Asp + 3ATP -> urea + fumarate
Occurs in the LIVER
Describe the preparatory step for the urea cycle
Glutamate reacts with 2ATP and HCO3- in carbamoylphosphate synthetase. Carbamoyl phosphate forms.
Describe step 1 in the urea cycle. Where does it occur?
Mitochondrial matrix
carbamoyl phosphate + ornithine -> citrulline by ornithine transcarbamoylase
Describe step 2 in the urea cycle.
Citrulline + ATP -> citrullyl-ATP intermediate + Arg -> Arginiosuccinate + AMP
by Arginiosuccinate synthetase
Describe step 3 in the urea cycle
Arginiosuccinate -> fumarate + Arg by Arginiosuccinase
Describe step 4 in the urea cycle
Arg + H2O -> urea + ornithine by Arginase
Why do we go through the urea cycle but fish don’t?
NH4+ is toxic to land mammals, so we’d lose a lot of water since water hydrates NH4+ (it’s soluble) when flushing it out. Fish are already surrounded by a bunch of water so they don’t have to worry about water loss
Why is it important for the urea cycle to consume ATP?
deltaG from ATP hydrolysis guarantees the reaction goes forward only (as well as Le Chatelier’s principle since urea is always removed when we use the restroom). We don’t want toxic NH4+ reactant to build up!
Describe regulation of the urea cycle
Amino acid breakdown increases, so glutamate levels increase. Glu reacts with Acetyl-CoA through the NAGS enzyme, which converts Glu into NAG. NAGS activity increases because of greater Glu levels. NAG then activates CPS1, which makes carbamoyl phosphate for the urea cycle
Where are the enzymes of the urea cycle found?
Carbamoylphosphate synthetase and ornithine transcarbomylase are in the mitochondrial matrix.
The rest are in the cytosol
What is the Asp-Arg shunt’s role?
To get some energy back from fumarate (2.5 ATP per fumarate)
Describe the Asp-Arg shunt
Fumarate gets reconverted into OAA like in TCA cycle, except this happens in the cytosol. Arginiosuccinate from the urea cycle converts into fumarate, which then converts to malate in the cytosol. The malate then converts to OAA for gluconeogenesis. OR, the fumarate can enter the matrix for the TCA cycle, which completes the shunt.