Abstract
Portal-systemic shunting of blood is associated with hyperammonemia, an increased glutamine concentration in brain, an altered plasma neutral amino acid pattern, and high levels of several of the large neutral amino acids in brain. Since some of these amino acids are precursors for neurotransmitters and for other potentially neuroactive substances, high CNS levels of these amino acids may contribute to the development of encephalopathy. In order to determine the relative importance of changes in brain glutamine levels and changes in competition among the neutral amino acids for blood-brain transport, we measured the concentrations of the large neutral amino acids in plasma, cisternal cerebrospinal fluid and in brain tissue from various regions of dogs after end-to-side portacaval shunt. Although the changes in CSF amino acid levels correlated partially with altered amino acid plasma competitor ratios, better correlations were observed with the elevation of CSF glutamine. These results suggest a model of blood-brain amino acid transport in which a high level of glutamine in brain extracellular fluid competes with other neutral amino acids for efflux from brain, thus raising brain amino acid levels after portalsystemic shunting
Highlights
One of the interesting problems in the study of hyperammonemia, liver failure and portal-systemic encephalopathy is the relationship of changes in the brain of the neurotransmitter-precursor amino acids to the development of encephalopathy
The changes in plasma concentrations of those amino acids would seem to predict18’11’15. The reason for this "excess" accumulation of large neutral amino acids (LNAA) in the CNS of patients or experimental animals with portal-systemic shunting and hyperammonemia has not been completely explained, data have been presented which point to a role for elevated glutamine concentrations in the CNS in altering LNAA
It should be noted that, due to the unpredictability of the course of encephalopathy after portacaval anastomosis (PCA) in dogs, it proved difficult to achieve the goal of equal numbers of dogs in each stage of encephalopathy
Summary
One of the interesting problems in the study of hyperammonemia, liver failure and portal-systemic encephalopathy is the relationship of changes in the brain of the neurotransmitter-precursor amino acids to the development of encephalopathy. The amino acids of particular interest are tyrosine, phenylalanine and tryptophan, since they are involved in the synthesis in the brain of catecholamines, serotonin and of potential false transmitters such as octopamine or tryptamine7’5 These amino acids, together with leucine, isoleucine, valine, methionine, threonine and histidine, comprise the group of large neutral amino acids (LNAA) which share a common blood-brain transport system. The changes in plasma concentrations of those amino acids would seem to predict18’11’15 The reason for this "excess" accumulation of LNAA in the CNS of patients or experimental animals with portal-systemic shunting and hyperammonemia has not been completely explained, data have been presented which point to a role for elevated glutamine concentrations in the CNS in altering LNAA transport at the blood-brain barrier1’12’13. The results point to a significant role of elevated brain GLN as a competitor for efflux of the LNAA from the brain to the blood
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
