| Tetrahydrobiopterin and cytokines. | |
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MedLine Citation:
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PMID: 8475129 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Biosynthesis of tetrahydrobiopterin starts from guanosine triphosphate by the action of guanosine triphosphate cyclohydrolase I, which yields the first intermediate, 7,8-dihydroneopterin triphosphate. This compound is then converted by subsequent enzymes, 6-pyruvoyl tetrahydropterin synthase and sepiapterin reductase, to tetrahydrobiopterin, the biologically active metabolite. Cytokines such as gamma-interferon or tumor necrosis factor-alpha strongly stimulate the activity of guanosine triphosphate cyclohydrolase I in murine and human cells, yielding a potentiation of intracellular tetrahydrobiopterin concentrations. In human cells, particularly in human monocytes and macrophages, the low activity of 6-pyruvoyl tetrahydropterin synthase leads to the additional accumulation of neopterin derivatives, which leak from the cells after dephosphorylation and are found increased in body fluids of humans with diseases challenging cell-mediated immunity. A functional role for the stimulation of tetrahydrobiopterin biosynthesis by cytokines is the formation of a limiting cofactor required for the enzymatic conversion of L-arginine to citrulline and nitric oxide. |
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Authors:
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E R Werner; G Werner-Felmayer; H Wachter |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) Volume: 203 ISSN: 0037-9727 ISO Abbreviation: Proc. Soc. Exp. Biol. Med. Publication Date: 1993 May |
Date Detail:
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Created Date: 1993-05-20 Completed Date: 1993-05-20 Revised Date: 2007-11-02 |
Medline Journal Info:
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Nlm Unique ID: 7505892 Medline TA: Proc Soc Exp Biol Med Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1-12 Citation Subset: IM |
Affiliation:
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Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Austria. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alcohol Oxidoreductases
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metabolism Animals Biopterin / analogs & derivatives*, biosynthesis Cytokines / pharmacology, physiology* GTP Cyclohydrolase / metabolism Humans Macrophages / drug effects, physiology Monocytes / drug effects, physiology Phosphorus-Oxygen Lyases* |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 17528-72-2/5,6,7,8-tetrahydrobiopterin; 22150-76-1/Biopterin; EC 1.1.-/Alcohol Oxidoreductases; EC 1.1.1.153/sepiapterin reductase; EC 3.5.4.16/GTP Cyclohydrolase; EC 4.6.-/Phosphorus-Oxygen Lyases; EC 4.6.10/6-pyruvoyltetrahydropterin synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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