1. Transamination to make aspartate
2. Condensation with acetyl CoA to make citrate -> energy
3. Gluconeogenesis -> energy export
4. Conversion to pyruvate then to Acetyl CoA for fatty acid synthesis

Michigan State University

- 1st amino group from ammonium, second amino group from aspartate, carbon comes from bicarbonate
- ** Fumarate is formed from the breakdown of argininosuccinate in the urea cycle, and links the urea cycle with the TCA cycle
- First reactions occur in the mitochondrial matrix

OVERVIEW
- Carbamoyl Phosphate synthesis
- Formation of Citrulline (in mitochondrial matrix)
- Formation of Argininosuccinate (cytoplasm)
- Formation of Fumarate
- Cleavage

- Eventually converted to OAA, cycle can start again


Urea Cycle

- Intermediate created: Carbamoyl phosphate
- Enzyme: Carbamoyl Phosphate Synthetase
> Requires ATP

> Major point of regulation

> 1. Activation of bicarbonate with ATP, to form carboxyphosphate

> 2. Addition of ammonium

> 3. Activation of carbamic acid with ATP to form carbamoyl phosphate

> Anhydride bond, higher transfer potential

- Carbamoyl Phosphate Synthetase is responsible for substrate channeling - prevents loss of intermediates


Carbamoyl Phosphate Synthesis

- Ornithine + Carbamoyl Phosphate -> Citrulline
- Enzyme: Ornithine transcarbamylase
- Citrulline is transported to the cytosol


Formation of Citrulline (in mitochondrial matrix)

- Reaction requires ATP and is driven forward by PPi cleavage
- Citrulline + Aspartate -> Argininosuccinate
- Enzyme: Argininosuccinate synthetase


Formation of Argininosuccinate (cytoplasm)

- Argininosuccinate -> Arginine + Fumarate
- Enzyme: Argininosuccinase
- Carbon Skeleton Link to TCA cycle

Formation of Fumarate

- Arginine -> Ornithine + Urea
- Enzyme: Arginase
- Ornithine transported from cytosol to MT (mitochondrial matrix) to join the urea cycle
- Urea given off in urine


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