Sulfur-containing amino acids in experimental hepatic coma in the dog and the monkey

Four dogs and five monkeys were subjected to end-to-side portacaval anastomosis (PCS) and alterations in plasma and cerebral spinal fluid (CSF) levels of the sulfur-containing amino acids (methionine, cysteine, taurine) studied during development of hepatic encephalopathy (HE). Methionine, cysteine, ammonia, phenylethanolamine, and octopamine levels rose in both species in plasma and CSF, while taurine levels increased significantly in monkey CSF and in dog plasma. Infusion of a branched-chain amino-acid-rich solution during encephalopathy rapidly reversed all neurolgical derangements and restored the deranged amino acid pattern to normal. The results confirm the observation that plasma levels of the sulfur-containing amino acids are elevated in HE and demonstrate similar changes in CSF, reflecting brain metabolism. It is suggested that a common transport mechanism for all neutral amino acids across the blood-brain barrier (BBB) causes accumulation of methionine in the brain. Methionine toxicity in chronic liver disease may be mediated in part through its metabolite taurine, which is a well-established inhibitory neurotransmitter, at least in monkeys, but apparently not in dogs. The administration of a branched-chain amino-acid-rich solution lowered the penetration ability of methionine through the BBB. As a result, the levels of plasma and CSF sulfur-containing amino acid levels returned to normal coincidentally with animals awakening from their comatose states.