Download 200 µmol /L is far too low a concentration of ammonium to affect

Ammonia toxicity
Ammonia is highly toxic. Normally blood ammonium concentration is < 50 µmol /L, and an
increase to only 100 µmol /L can lead to disturbance of consciousness. A blood ammonium
concentration of 200 µmol /L is associated with coma and convulsions.
200 µmol /L is far too low a concentration of ammonium to affect plasma pH or the normal
transport of sodium and potassium ions across nerve cell membranes.
The explanation of the toxicity of
such (relatively) low concentrations
of ammonium lies with the enzyme
glutamate dehydrogenase. This
enzyme catalyses the oxidative
deamination of glutamate to
ammonium and ketoglutarate; the
reaction is readily reversible, and the
direction of reaction (towards
deamination of glutamate or
glutamate formation) depends on the
relative concentrations of the various
substrates. As the concentration of
ammonium rises, so the reaction proceeds in the direction of formation of glutamate from
ketoglutarate.
The effect of forming glutamate from ketoglutarate is to deplete the mitochondrial pool of
ketoglutarate, which is a key intermediate in the citric acid cycle. As a result, the rate of citric
acid cycle activity falls, so reducing very considerably the rate of formation of ATP.
It is this lack of ATP that affects ion transport across nerve cell membranes, so resulting in
disturbance, then loss, of consciousness.
Formation of glutamine
Ammonium is produced in most cells of the body, as a result of deamination of amino acids and
amines. It is exported into the bloodstream as glutamine, formed by the actions of glutamate
dehydrogenase, to form glutamate from ketoglutarate and ammonium, then glutamine synthetase,
forming glutamine from glutamate and ammonium.