Oxaloacetate has four major metabolic fates:

1. **Transamination** to form aspartate.
2. **Condensation** with acetyl-CoA to form citrate for energy.
3. **Gluconeogenesis** for energy export.
4. **Conversion to pyruvate**, which is then converted to acetyl-CoA for fatty acid synthesis.

Michigan State University

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- 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

- 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


Cleavage

Four Fates of Oxaloacetate

In the urea cycle, carbamoyl phosphate and ornithine combine to form citrulline within the mitochondrial matrix. This reaction is catalyzed by the enzyme ornithine transcarbamylase. Once formed, citrulline is transported across the mitochondrial membrane into the cytosol.

$$\text{Ornithine} + \text{Carbamoyl Phosphate} \rightarrow \text{Citrulline}$$

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