Inhibition of GTP cyclohydrolase I by pterins.
Pterins inhibit rat liver GTP cyclohydrolase I activity noncompetitively. Reduced pterins, such as 7,8-dihydro-D-neopterin, (6R,S)-5,6,7,8-tetrahydro-D-neopterin, 7,8-dihydro-L-biopterin, (6R)-5,6,7,8-tetrahydro-L-biopterin, L-sepiapterin, and DL-6-methyl-5,6,7,8-tetrahydropterin are approximately 12-times more potent as inhibitors than are oxidized pterins, such as D-neopterin, L-biopterin, and isoxanthopterin. They are also 12-times more potent than folates, such as folic acid, dihydrofolic acid, (+/-)-L-tetrahydrofolic acid, and aminopterin. The Ki values for 7,8-dihydro-D-neopterin, 7,8-dihydro-L-biopterin, and (6R)-5,6,7,8-tetrahydro-L-biopterin are 12.7 microM, 14.4 microM, and 15.7 microM, respectively. These results suggest that mammalian GTP cyclohydrolase I may be regulated by its metabolic end products.
Shen
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RS
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
Alam
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A
Zhang
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D000619:Aminohydrolases / Q000037:antagonists & inhibitors*; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000494:pharmacology; D005492:Folic Acid / Q000494:pharmacology; D006136:GTP Cyclohydrolase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D019798:Neopterin / Q000031:analogs & derivatives; D010084:Oxidation-Reduction; D011621:Pteridines / Q000494:pharmacology; D011622:Pterins / Q000494:pharmacology*; D051381:Rats; D014976:Xanthopterin / Q000494:pharmacology
D011621:Pteridines; D011622:Pterins; C000976:7,8-dihydroneopterin; D001708:Biopterins; C008217:isoxanthopterin; D019798:Neopterin; C017226:7,8-dihydrobiopterin; D005492:Folic Acid; C017523:6-methyltetrahydropterin; C016727:sepiapterin; D000619:Aminohydrolases; D006136:GTP Cyclohydrolase; C003402:sapropterin; D014976:Xanthopterin