Hepatic encephalopathy tryptophan

Because the hver metabohzes the aromatic amino acids (i.e., phenylalanine, tyrosine, and tryptophan), methionine, and glutamine, the plasma concentrations of these amino acids are elevated in cirrhotic patients. Plasma concentrations of the branched-chain amino acids (BCAAs) (i.e., valine, leucine, and isoleucine) often are depressed because these amino acids are metabohzed by skeletal muscle. This altered plasma aminogram contributes to the development of hepatic encephalopathy. 

Moroni F, Lombardi G, Carla V, Pellegrini D, Carassale GL, Cortesini C. Content of quinolinic acid and other tryptophan metabolites increases in brain regions of rats used as experimental models of hepatic encephalopathy. J. Neurochem., 46, 869-874, 1986a Moroni F, Lombardi G, Carla V, Lai S, Etienne P, Neiir NPV. Increase in the content of quinolinic acid in cerebrospinal fluid and frontal cortex of patients with hepatic failure. J. Neurochem., 47, 1667-1671, 1986b... 

In liver failure the plasma concentrations of the aromatic amino acids (AAAs) tyrosine, phenylalanine, and tryptophan increase, probably because they are predominantly broken down in the liver, whereas the plasma levels of BCAAs decrease while they are degraded in excess in muscle as a consequence of hepatic failure-induced catabolism. As AAAs and BCAAs are all neutral amino acids and share a common transporter across the blood-brain barrier (system L carrier), changes in their plasma ratio are reflected in the brain, subsequently disrupting the neurotransmitter profile of the catecholamines and indoleamines (see sections on tyrosine and tryptophan). It has been hypothesized that this disturbance contributes to the multifactorial pathogenesis of hepatic encephalopathy. In line with this hypothesis it has been suggested that normalization of the amino acid pattern by supplementing extra BCAAs counteracts hepatic encephalopathy. 

Since BCAAs compete with tryptophan for uptake by the brain, they have (in line with the ascribed benefits in hepatic encephalopathy) been applied as competitive antagonists for tryptophan transport, reducing tryptophan-induced cognitive impairment (see also section on tryptophan). 

A study by Rao et al." measured the levels of amino acids using in vivo cerebral microdialysis in the frontal cortex of portacaval-shunted rats administered ammonium acetate to precipitate severe portal-systemic encephalopathy. In comparison to sham-operated control rats, tryptophan levels increased by 63% along with those of other amino acids. However, the experimental animals did not have a significant increase in extracellular fluid concentration of tryptophan, suggesting that increased spontaneous release of tryptophan in cerebral cortex is not implicated in the pathogenesis of hepatic coma. 

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