Evidence of a vicious cycle in glutamine synthesis and breakdown in pathogenesis of hepatic encephalopathy-thereapeutic perspectives
Abstrakt
The article provides evidence that a vicious cycle in glutamine synthesis and breakdown among tissues with high levels of glutamine synthetase (skeletal muscle, brain) and glutaminase (enetrocytes, kidneys) is activated in liver failure. These alterations may explain why therapies targeted to intestinal bacteria have only a limited effect on ammonia levels in patients with liver failure and indicate the needs of new therapeutic strategies focused on glutamine metabolism.
The positive and adverse effects of various nutritional and pharmacological strategies focused on glutamine metabolism in treatment of hyperammonemia and hepatice encephalopathy are discussed in the second part of the article. Attention is given to glutamine, glutamate, alpha-ketoglutarate, branched-chain amino acids, glutaminase inhibitors, and phenylbutyrate.