Urea Cycle

The mechanism by which nitrogen is exposed of, which is both toxic and could otherwise form excess glutamine from alpha-ketoglutarate. Excess glutamine will limit the synthesis of the neurotransmitter glutamate.

Urea is created in the liver from protein degradation products.

Source of Nitrogen

Made from bicarbonate which is attached to two amine groups. Deamination of the amino groups provides the ammonia for the urea cycle.

The urea cycle recycles products from both the TCA and gluconeogenesis. In the TCA, when arginosuccinate is converted to arginine, fumarate is produced, generating an amine molecule which is processed by the urea cycle. The fumarate can then be converted to malate and oxidized to oxaloacetate for gluconeogenesis.

In gluconeogenesis, one amino group is taken from the amino acid deamination and the second donated from aspartate. Aspartate is made in the mitochondrial matrix with oxaloacetate. It is transported to the cytosol for this amination reaction.

Regulation

Carbamoyl Phosphate Synthase I (CPS I)

This enzyme produces carbamoyl phosphate from bicarbonate. It is activated by N-acetyl glutamate, which is active when glutamate levels are high to support urea production.

Ornithine

Carbonyl phosphate and ornithine react to continue the cycle. Ornithine is created from arginine and glutamate. Therefore, if any of the glucogenic amino acids become scarce, ornithine/urea production slows down.

TCA intermediates

Aspartate is formed in the TCA cycle. If the TCA cycle does not get intermediates, it will slow down as will the urea cycle.