Principles of Biochemistry, Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
Oxidative Degradation of Amino Acids. The Urea Cycle
Ammonia is transported to the liver from many peripheral tissues in the form of glutamine

Let us now address the following question: how is toxic ammonia transported from peripheral Tissues to the Organs responsible for its detoxification or excretion without endangering the Brain?

In most animals, ammonia is first converted into a nontoxic compound and only then transported via the bloodstream from peripheral tissues to the Liver or Kidneys. In many tissues, including the brain, ammonia reacts with glutamate in an enzymatic reaction catalyzed by Glutamine Synthetase, yielding glutamine.

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This reaction proceeds via The formation of a high-energy enzyme-bound intermediate (Fig. 19-13). This intermediate is $\gamma$-glutamyl phosphate, an acyl phosphate formed by the phosphorylation of the 5-carboxyl group of glutamate (at the expense of ATP). The enzyme-bound $\gamma$-glutamyl phosphate then reacts with ammonia at the Active Site of glutamine synthetase to form glutamine and release inorganic phosphate. Glutamine is a neutral, nontoxic compound that readily crosses Cell membranes, distinguishing it from glutamate, which cannot do so because its molecules carry a net negative charge (Fig. 5-6).

Fig. 19-13. Formation of $\gamma$-glutamyl phosphate as an enzyme-bound intermediate in the glutamine synthetase reaction.

In most terrestrial animals, glutamine is carried by the Blood to the liver, where it is converted back into glutamate and ammonia by the action of the enzyme glutaminase.

The ammonia thus released is subsequently converted into urea in the liver. Glutamine serves as the primary vehicle for Ammonia Transport; in the blood of healthy individuals, its concentration significantly exceeds that of any other amino acid.