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Pathway Description
Pterine Biosynthesis
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-01-21
Last Updated: 2019-09-15
Folates are very important cofactors that provide support for many biosynthetic reactions. The reactions depicted in this pathway include reactions that are paired with transports, within the cell, travelling intracellularly, which allows folate to be absorbed by cells, as well as the synthesis of pterines, which are used in folate synthesis. Two branches are depicted: Pterin synthesis and Folate biosynthesis. In pterin synthesis, GTP is the precursor for pterin biosynthesis. In the first reaction, GTP cyclohydrolase acts to create formamidopyrimidine nucleoside triphosphate from guanosine triphosphate, which is provided from the purine metabolism pathway. Formamidopyrimidine nucleoside triphosphate then uses GTP cyclohydrolase again to create 2,5-diaminopyrimidine nucleoside triphosphate. GTP cyclohydrolase then works with 2,5-diaminopyrimidine nucleoside triphosphate to produce 2,3-diamino-6-(5’-triphosphoryl-3’,4’-trihydroxy-2’-oxopentyl)-amino-4-oxopyrimidine, which is then converted by GTP cyclohydrolase to dihydroneopterin triphosphate. Dihydroneopterin is then transported to the mitochondria and subsequently catalyzed into dyspropterin, which then exits the mitochondria to continue pterin biosynthesis. Once having been transported from the mitochondria, dyspropterin uses sepiapterin reductase, aldose reductase and carbonyl reductase [NADPH] 1 to create 6-lactoyltetrahydropterin. This compound then undergoes 2 reactions, the first being sepiapterin reductase converting 6-lactoyltetrahydropterin into tetrahydrobiopterin, the second being 6-lactoyltetrahydropterin being converted to sepiapterin. Both branches of pterin reactions then respectively end in the creation of neopterin and dihydrobiopterin.
References
Pterine Biosynthesis References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
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Pubmed: 10727395
Longo N: Disorders of biopterin metabolism. J Inherit Metab Dis. 2009 Jun;32(3):333-42. doi: 10.1007/s10545-009-1067-2. Epub 2009 Feb 9.
Pubmed: 19234759
Nomura T, Ichinose H, Sumi-Ichinose C, Nomura H, Hagino Y, Fujita K, Nagatsu T: Cloning and sequencing of cDNA encoding mouse GTP cyclohydrolase I. Biochem Biophys Res Commun. 1993 Mar 15;191(2):523-7. doi: 10.1006/bbrc.1993.1249.
Pubmed: 8461009
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Pubmed: 15489334
Gutlich M, Schott K, Werner T, Bacher A, Ziegler I: Detection and quantification of GTP cyclohydrolase I mRNA. Adv Exp Med Biol. 1993;338:167-70. doi: 10.1007/978-1-4615-2960-6_32.
Pubmed: 8304101
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Pubmed: 16141072
Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villen J, Haas W, Sowa ME, Gygi SP: A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010 Dec 23;143(7):1174-89. doi: 10.1016/j.cell.2010.12.001.
Pubmed: 21183079
Turri MO, Ilg EC, Thony B, Blau N: Structure, genomic localization and recombinant expression of the mouse 6-pyruvoyl-tetrahydropterin synthase gene. Biol Chem. 1998 Dec;379(12):1441-7.
Pubmed: 9894812
Ota A, Ichinose H, Nagatsu T: Mouse sepiapterin reductase: an enzyme involved in the final step of tetrahydrobiopterin biosynthesis. Primary structure deduced from the cDNA sequence. Biochim Biophys Acta. 1995 Feb 21;1260(3):320-2. doi: 10.1016/0167-4781(94)00225-r.
Pubmed: 7873607
Lee SW, Park IY, Hahn Y, Lee JE, Seong CS, Chung JH, Park YS: Cloning of mouse sepiapterin reductase gene and characterization of its promoter region. Biochim Biophys Acta. 1999 Apr 14;1445(1):165-71. doi: 10.1016/s0167-4781(99)00030-5.
Pubmed: 10209270
Maier J, Schott K, Werner T, Bacher A, Ziegler I: Northern blot analysis of sepiapterin reductase mRNA in mammalian cell lines and tissues. Adv Exp Med Biol. 1993;338:195-8. doi: 10.1007/978-1-4615-2960-6_39.
Pubmed: 8304109
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000005
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