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7-Substituted pterins. A new class of mammalian pteridines.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 1990 Mar 05; Vol. 265 (7), pp. 3923-30. - Publication Year :
- 1990
-
Abstract
- Three novel pteridines have been isolated from the urine of patients with a new variant of 6-(L-erythro-1',2'-dihydroxypropyl)-5,6,7,8-tetrahydropterin (tetrahydrobiopterin) deficiency, showing hyperphenylalaninemia. From the results of high performance liquid chromatography, oxidative degradation, and gas chromatography-electron impact mass spectrometry, their structures were identified as 7-(D-erythro-1',2',3'-trihydroxypropyl)-pterin (7-neopterin), 7-(L-erythro-1',2'-dihydroxypropyl)-pterin (7-biopterin), and 6-oxo-7-(L-erythro-1',2'-dihydroxypropyl)-pterin (6-oxo-7-biopterin). The ratio of biopterin to 7-biopterin in the patients' urines was 1:1, and after oral loading with tetrahydrobiopterin, 7-biopterin excretion rose parallel to biopterin. This finding suggests that 7-substituted pterins may be formed endogenously by a yet unknown isomerization reaction. The cause of hyperphenylalaninemia is still unclear. The activities of the enzymes involved in tetrahydrobiopterin biosynthesis and regeneration were found to be normal in the patients, and no effect of 7-biopterin on these enzymes was observed in vitro. However, compared with the normal cofactor, tetrahydrobiopterin, the Km values of tetrahydro-7-biopterin for phenylalanine hydroxylase and dihydropteridine reductase are 20 and 5 times higher, respectively.
- Subjects :
- Chromatography, High Pressure Liquid
Dihydropteridine Reductase metabolism
Erythrocytes analysis
GTP Cyclohydrolase metabolism
Gas Chromatography-Mass Spectrometry
Humans
Indicators and Reagents
Isomerism
Leukocytes analysis
Liver enzymology
Male
Oxidation-Reduction
Phenylalanine Hydroxylase metabolism
Pteridines blood
Pteridines pharmacology
Pterins blood
Pterins pharmacology
Structure-Activity Relationship
Pteridines urine
Pterins urine
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 265
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 2303485