Hepatic coma and amino acids in the nerve endings of the central nervous system.

The levels of amino acids in the cerebral cortex and synaptosomes of 6 autopsied patients who had died of chronic liver diseases with portasystemic shunt were examined and compared with those of controls. The level of threonine in the cerebral cortex and synaptosomes of the 6 patients, who had developed hepatic coma before death, was significantly higher than that of 9 patients without hepatic coma. However, the levels of the neurotransmitters, aspartate, glutamate, and glycine, showed no significant difference between the two groups. In animal experiments, threonine uptake into the synaptosomes was enhanced by an increase of threonine concentration in the cerebral cortex, and at the same time ammonia further promoted threonine uptake. The high level of threonine in the synaptosomes was released just like a neurotransmitter on potassium stimulation in the patients with hepatic coma. Since threonine has no post-synaptic action, it is thought that threonine released in this way somehow interferes with brain action. This phenomenon may play an important role in the development of hepatic coma.