蝶呤对GTP环化水解酶I的抑制作用。

Inhibition of GTP cyclohydrolase I by pterins.

作者信息

Shen R S, Alam A, Zhang Y X

机构信息

Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.

出版信息

Biochim Biophys Acta. 1988 Apr 14;965(1):9-15. doi: 10.1016/0304-4165(88)90144-4.

DOI:10.1016/0304-4165(88)90144-4

PMID:3349105

Abstract

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.

摘要

蝶呤非竞争性抑制大鼠肝脏鸟苷三磷酸环化水解酶I的活性。还原型蝶呤，如7,8-二氢-D-新蝶呤、(6R,S)-5,6,7,8-四氢-D-新蝶呤、7,8-二氢-L-生物蝶呤、(6R)-5,6,7,8-四氢-L-生物蝶呤、L-异喋呤和DL-6-甲基-5,6,7,8-四氢蝶呤作为抑制剂的效力比氧化型蝶呤，如D-新蝶呤、L-生物蝶呤和异黄蝶呤高约12倍。它们的效力也比叶酸，如叶酸、二氢叶酸、(+/-)-L-四氢叶酸和氨甲蝶呤高12倍。7,8-二氢-D-新蝶呤、7,8-二氢-L-生物蝶呤和(6R)-5,6,7,8-四氢-L-生物蝶呤的Ki值分别为12.7微摩尔、14.4微摩尔和15.7微摩尔。这些结果表明，哺乳动物鸟苷三磷酸环化水解酶I可能受其代谢终产物的调节。