At cellular pH NH3 exists as NH4+ ion.

If the concentration of ammonium ions is

very high, coma may result ( Hepatic coma).

There are mechanisms in our body to avoid hyperammonemia. Those mechanisms

allow the transport of ammonia from muscle and other peripheral tissues to the liver
and the kidneys.

In the liver, the ammonia delivered by these mechanisms will form UREA, while in
the kidneys these mechanism will allow the direct excretion of NH4+ in urine.

These mechanisms are:

Glucose-alanine cycle (transport of NH3 from muscle to liver).

Glutamine synthase/glutaminase system (transport of NH3 from different tissues

to kidney and liver)

Ammonia Detoxification in Muscle:

Alanine transaminase has an important function in the delivery of skeletal muscle

carbon and nitrogen (in the form of alanine) to the liver. In the glucose-alanine
cycle(CAHILL cycle) ammonium ion is transported from muscle cells to the liver
in the form of alanine.

Through glycolysis, glucose becomes pyruvate in the muscle. The participation of

this ketoacid (pyruvate) intransamination reactions produce the corresponding
amino acid: alanine. Alanine is then transported to the liver, where it can be
transaminated again producing pyruvate that can be used for gluconeogenesis
yielding glucose that can be send again to the muscle for producing energy
(glucose-alanine cycle).

Cahill
cycle
The other mechanism for transporting nitrogen in a non toxic form from the muscle
to the liver is in form of glutamine. The enzyme glutamine synthase (also present in
the liver) catalyses the following reaction:
Glutamate + NH3 + ATP - glutamine +ADP + (P)

This reaction allows the transportation of nitrogen in a non toxic form to the liver
and kidney (this reaction is important for other things, also!). Glutamine is the major
amino acid found in the circulatory system, followed by alanine. The role of
glutamine in the blood is to carry ammonia to and from various tissues but
principally from peripheral tissues like the muscle, to the kidney and liver, where
the amide nitrogen is hydrolyzed by the enzyme glutaminase and the ammonia is
released, forming H4+ ion. In the kidney, it can be excreted in the urine by direct
renal excretion, while in the liver the ammonia released by glutaminase will be used
mainly for the synthesis of urea.

Note that ammonia arising in muscle and other peripheral tissues is carried in a
nonionizable form as alanine or glutamine from to the liver. In these forms,
ammonia does not have the toxic properties of free ammonia.

Relationship between pyridoxal 5'-phosphate deficiency and

aminotransferase levels in alcoholic hepatitis.
Diehl AM, Potter J, Boitnott J, Van Duyn MA, Herlong HF, Mezey E.
Abstract
The relationship between pyridoxal phosphate deficiency and activities of serum and liver
aminotransferases was studied in 12 patients with alcoholic hepatitis. Plasma pyridoxal phosphate and
the activities of liver aminotransferases were initially decreased in the patients, as compared with mean
values in controls with normal hepatic histology. Addition of pyridoxal phosphate to liver homogenates
increased liver alanine aminotransferase, but not aspartate aminotransferase, in all patients with initially
low plasma pyridoxal phosphate. After 1 mo of abstinence from alcohol, with intake of an adequate diet
and pyridoxine supplementation, plasma pyridoxal phosphate increased in all patients with initially low
values (p less than 0.02). Serum aspartate aminotransferase decreased, whereas serum alanine
aminotransferase increased, resulting in a decrease in their ratio in serum (p less than 0.001). Liver
alanine aminotransferase increased (p less than 0.005), whereas liver aspartate aminotransferase
remained unchanged. These data suggest that pyridoxal 5'-phosphate depletion is partially responsible
for the low serum alanine to aspartate aminotransferase ratio that is typical of patients with alcoholic
hepatitis.