Higher plants synthesize a diversified array of non-protein amino acids many of which bear marked structural analogy to the amino acids of mammalian metabolism. As a result, these secondary plant constituents are usually highly toxic and exhibit pronounced antimetabolic properties in animals. A particular group of naturally occurring non-protein amino acids, namely L-canavanine, L-canaline, and O-ureido-L-homoserine, are structurally related to the intermedates of the Krebs-Henseleit ornithine-urea cycle of animals. This group of non-protein amino acids will be utilzed as a model for understanding the biochemical basis for the toxicity and mode of action of these toxic amino acids. Emphasis will be placed on improving the utility of these compounds in fundamental biochemical studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM017322-11
Application #
3151051
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1978-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
11
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Type
Graduate Schools
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506
Thomas, D A; Rosenthal, G A (1987) Toxicity and pharmacokinetics of the nonprotein amino acid L-canavanine in the rat. Toxicol Appl Pharmacol 91:395-405
Rosenthal, G A; Dahlman, D L (1986) L-Canavanine and protein synthesis in the tobacco hornworm Manduca sexta. Proc Natl Acad Sci U S A 83:14-8
Rosenthal, G A; Thomas, D A (1985) A radiometric assay for determining the incorporation of L-canavanine or L-arginine into protein. Anal Biochem 147:428-31