American Journal of Clinical Nutrition, Vol 26, 916-925, Copyright © 1973 by The American Society for Clinical Nutrition, Inc.

Comparison of the effect of various amino acids upon the blood ammonia concentration of patients with liver disease

¹ From the Departments of Medicine, Biochemistry, and Surgery, Emory University School of Medicine, and the Clinical Research Facility, Emory University Hospital, Atlanta, Georgia 30322

In six cirrhotic patients with a history of hepatic encephalopathy, the effect on blood NH₃ concentration of 18 amino acids and of urea was measured. Blood NH₃ was determined before and 2, 4, and 6 hr after ingestion of the test material. Each preparation was tested at doses representing 0.00088 to 0.45 g N/per kg body wt^3/4.

Ten of eighteen amino acids caused a rise in blood NH₃, usually maximal at 4 hr. The smallest dose (minimal effective dose) of each of these amino acids that elevated blood NH₃ by 50 or by 100 µg/100 ml at 4 hr was determined. Glycine was assigned an ammonigenic potency of 100. The potency of each test material in each subject was calculated as:

[See equation in the PDF file]

with an increment of either 50 or 100 µg/100 ml as the threshold effect.

On the basis of ammonigenic potencies, the 18 amino acids and urea can be divided into three groups: group A (potency 40 to 160): glycine, serine, threonine, glutamine, histidine, lysine, and asparagine; group B (9 to 25): leucine, alanine, valine, phenylalanine, isoleucine, tyrosine, and proline; group C (< 7): arginine, aspartic acid, glutamic acid, tryptophan, and urea. The high potency of group A amino acids may reflect production of NH₃ in the initial reaction of metabolic degradation (deamination or deamidation). The low potency of groups B and C may be explained by catabolism proceeding initially via transamination, with the amino groups entering the Krebs-Henseleit cycle via aspartic acid rather than NH₃. The hypothesis was supported by 1) failure of neomycin to alter the oral ammonigenic potencies of glycine, serine, lysine, phenylalanine, leucine, and alanine; and 2) by a similar order of ammonigenic potencies for glycine, serine, threonine, glutamine, valine, phenylalanine, arginine, glutamic acid, and aspartic acid, whether tested by the oral or the intravenous route.