Document Detail

Biosynthesis of tetrahydrobiopterin by de novo and salvage pathways in adrenal medulla extracts, mammalian cell cultures, and rat brain in vivo.
MedLine Citation:
PMID:  6572916     Owner:  NLM     Status:  MEDLINE    
Mammalian cells and tissues were found to have two pathways for the biosynthesis of tetrahydrobiopterin (BH4): (i) the conversion of GTP to BH4 by a methotrexate-insensitive de novo pathway, and (ii) the conversion of sepiapterin to BH4 by a pterin salvage pathway dependent on dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase, EC activity. In a Chinese hamster ovary cell mutant lacking dihydrofolate reductase (DUKX-B11), endogenous formation of BH4 proceeds normally but, unlike the parent cells, these cells or extracts of them do not convert sepiapterin or 7,8-dihydrobiopterin to BH4. KB cells, which do not contain detectable levels of GTP cyclohydrolase or BH4 but do contain dihydrofolate reductase, readily convert sepiapterin to BH4 and this conversion is completely prevented by methotrexate. In supernatant fractions of bovine adrenal medulla, the conversion of sepiapterin to BH4 is completely inhibited by methotrexate. Similarly, this conversion in rat brain in vivo is methotrexate-sensitive. Sepiapterin and 7,8-dihydrobiopterin apparently do not enter the de novo pathway of BH4 biosynthesis and may be derived from labile intermediates which have not yet been characterized.
C A Nichol; C L Lee; M P Edelstein; J Y Chao; D S Duch
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  80     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1983 Mar 
Date Detail:
Created Date:  1983-05-05     Completed Date:  1983-05-05     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1546-50     Citation Subset:  IM    
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MeSH Terms
Adrenal Medulla / metabolism*
Biopterin / analogs & derivatives,  biosynthesis*
Brain / metabolism*
Cells, Cultured
Guanosine Triphosphate / metabolism
Methotrexate / pharmacology
Pteridines / biosynthesis*,  metabolism
Reg. No./Substance:
0/Pteridines; 0/Pterins; 17094-01-8/sepiapterin; 17528-72-2/5,6,7,8-tetrahydrobiopterin; 22150-76-1/Biopterin; 59-05-2/Methotrexate; 86-01-1/Guanosine Triphosphate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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