Effects of Keto Analogues of Essential Amino Acids in Portal-Systemic Encephalopathy

W. C. Maddrey, F. L. Weber, A. W. Coulter, C. M. Chura, N. P. Chapanis, M. Walser

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Keto analogues of five essential amino acids (valine, leucine, isoleucine, methionine, and phenylalanine) were given either parenterally or orally in varying proportions to 11 patients with portal-systemic encephalopathy and hyperammonemia. Plasma concentrations of amino acids corresponding to the infused analogues, including alloisoleucine, increased significantly after infusions. Plasma tyrosine and glycine, which were abnormally elevated in control samples, fell after the infusions. After one to five daily infusions, the ratio of essential to nonessential amino acids in fasting plasma was increased toward normal, suggesting improved protein nutrition. Arterial blood ammonia and glutamate did not change immediately after infusions, but a pronounced decrease in glutamine (42%) was observed. Eight nitrogen balance studies performed in 5 patients during 3 to 12 days of oral or intravenous keto acid therapy failed to show consistent improvement in balance as compared with control periods. After five courses of oral therapy there was again significant improvement in the ratio of essential to nonessential amino acids. No toxicity from keto analogue administration was found, and clinical improvement, as assessed by mental status and psychological testing occurred in 8 of 11 patients. These studies suggest keto analogues of essential amino acids are converted to the corresponding amino acids in patients with portal-systemic encephalopathy, and that such therapy may be of benefit.

Original languageEnglish (US)
Pages (from-to)190-195
Number of pages6
JournalGastroenterology
Volume71
Issue number2
DOIs
StatePublished - Jan 1 1976

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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