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Pathway Description
Dihydropyrimidine Dehydrogenase Deficiency (DHPD)
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2013-08-19
Last Updated: 2022-10-24
Dihydropyrimidine Dehydrogenase Deficiency (DHPD; Thymine-uraciluria) is a rare autosomal recessive disorder caused by a mutation in the DPYD gene which codes for dihydropyrimidine dehydrogenase. A deficiency in this enzyme results in accumulation of 5-hydroxymethyluracil, thymine, and uracil in urine. Symptoms include nystagmus, large liver, hypotonia, growth and mental retardation, and seizures.
References
Dihydropyrimidine Dehydrogenase Deficiency (DHPD) References
[Wikipedia: Dihydropyrimidine dehydrogenase deficiency](http://en.wikipedia.org/wiki/Dihydropyrimidine_dehydrogenase_deficiency)
[Uniprot: Q12882](http://www.uniprot.org/uniprot/Q12882)
[OMIM: Entry 274270](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=274270)
Engelke, U., van der Graaf, M., Heerschap, A., Hoenderop, S., Moolenaar, S., Morava, E., Wevers, R. Handbook of 1H-NMR spectroscopy in inborn errors of metabolism: body fluid NMR spectroscopy and in vivo MR spectroscopy (2nd ed) (2007) p.36 Heilbronn: SPS Verlagsgesellschaft
Berger R, Stoker-de Vries SA, Wadman SK, Duran M, Beemer FA, de Bree PK, Weits-Binnerts JJ, Penders TJ, van der Woude JK: Dihydropyrimidine dehydrogenase deficiency leading to thymine-uraciluria. An inborn error of pyrimidine metabolism. Clin Chim Acta. 1984 Aug 31;141(2-3):227-34.
Pubmed: 6488556
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Pubmed: 10071185
Brockstedt M, Jakobs C, Smit LM, van Gennip AH, Berger R: A new case of dihydropyrimidine dehydrogenase deficiency. J Inherit Metab Dis. 1990;13(1):121-4.
Pubmed: 2109146
Gonzalez FJ, Fernandez-Salguero P: Diagnostic analysis, clinical importance and molecular basis of dihydropyrimidine dehydrogenase deficiency. Trends Pharmacol Sci. 1995 Oct;16(10):325-7.
Pubmed: 7491709
Glycine and Serine Metabolism References
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Pubmed: 3418353
Bach AW, Lan NC, Johnson DL, Abell CW, Bembenek ME, Kwan SW, Seeburg PH, Shih JC: cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4934-8. doi: 10.1073/pnas.85.13.4934.
Pubmed: 3387449
Chen ZY, Hotamisligil GS, Huang JK, Wen L, Ezzeddine D, Aydin-Muderrisoglu N, Powell JF, Huang RH, Breakefield XO, Craig I, et al.: Structure of the human gene for monoamine oxidase type A. Nucleic Acids Res. 1991 Aug 25;19(16):4537-41. doi: 10.1093/nar/19.16.4537.
Pubmed: 1886775
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Pubmed: 8561277
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Pubmed: 3582651
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Pubmed: 3562250
Edgar AJ, Polak JM: Molecular cloning of the human and murine 2-amino-3-ketobutyrate coenzyme A ligase cDNAs. Eur J Biochem. 2000 Mar;267(6):1805-12. doi: 10.1046/j.1432-1327.2000.01175.x.
Pubmed: 10712613
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Pubmed: 14702039
Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. doi: 10.1038/990031.
Pubmed: 10591208
Binzak BA, Vockley JG, Jenkins RB, Vockley J: Structure and analysis of the human dimethylglycine dehydrogenase gene. Mol Genet Metab. 2000 Mar;69(3):181-7. doi: 10.1006/mgme.2000.2980.
Pubmed: 10767172
Binzak BA, Wevers RA, Moolenaar SH, Lee YM, Hwu WL, Poggi-Bach J, Engelke UF, Hoard HM, Vockley JG, Vockley J: Cloning of dimethylglycine dehydrogenase and a new human inborn error of metabolism, dimethylglycine dehydrogenase deficiency. Am J Hum Genet. 2001 Apr;68(4):839-47. doi: 10.1086/319520. Epub 2001 Feb 28.
Pubmed: 11231903
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Pubmed: 10444331
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Pubmed: 15164053
Kure S, Narisawa K, Tada K: Structural and expression analyses of normal and mutant mRNA encoding glycine decarboxylase: three-base deletion in mRNA causes nonketotic hyperglycinemia. Biochem Biophys Res Commun. 1991 Feb 14;174(3):1176-82. doi: 10.1016/0006-291x(91)91545-n.
Pubmed: 1996985
Kume A, Koyata H, Sakakibara T, Ishiguro Y, Kure S, Hiraga K: The glycine cleavage system. Molecular cloning of the chicken and human glycine decarboxylase cDNAs and some characteristics involved in the deduced protein structures. J Biol Chem. 1991 Feb 15;266(5):3323-9.
Pubmed: 1993704
Hayasaka K, Nanao K, Takada G, Okamura-Ikeda K, Motokawa Y: Isolation and sequence determination of cDNA encoding human T-protein of the glycine cleavage system. Biochem Biophys Res Commun. 1993 Apr 30;192(2):766-71. doi: 10.1006/bbrc.1993.1480.
Pubmed: 7916605
Nanao K, Takada G, Takahashi E, Seki N, Komatsu Y, Okamura-Ikeda K, Motokawa Y, Hayasaka K: Structure and chromosomal localization of the aminomethyltransferase gene (AMT) Genomics. 1994 Jan 1;19(1):27-30.
Pubmed: 8188235
Yang X, Wang Z, Li X, Liu B, Liu M, Liu L, Chen S, Ren M, Wang Y, Yu M, Wang B, Zou J, Zhu WG, Yin Y, Gu W, Luo J: SHMT2 Desuccinylation by SIRT5 Drives Cancer Cell Proliferation. Cancer Res. 2018 Jan 15;78(2):372-386. doi: 10.1158/0008-5472.CAN-17-1912. Epub 2017 Nov 27.
Pubmed: 29180469
Minton DR, Nam M, McLaughlin DJ, Shin J, Bayraktar EC, Alvarez SW, Sviderskiy VO, Papagiannakopoulos T, Sabatini DM, Birsoy K, Possemato R: Serine Catabolism by SHMT2 Is Required for Proper Mitochondrial Translation Initiation and Maintenance of Formylmethionyl-tRNAs. Mol Cell. 2018 Feb 15;69(4):610-621.e5. doi: 10.1016/j.molcel.2018.01.024.
Pubmed: 29452640
Feigenbaum AS, Robinson BH: The structure of the human dihydrolipoamide dehydrogenase gene (DLD) and its upstream elements. Genomics. 1993 Aug;17(2):376-81. doi: 10.1006/geno.1993.1335.
Pubmed: 8406489
Otulakowski G, Robinson BH: Isolation and sequence determination of cDNA clones for porcine and human lipoamide dehydrogenase. Homology to other disulfide oxidoreductases. J Biol Chem. 1987 Dec 25;262(36):17313-8.
Pubmed: 3693355
Pons G, Raefsky-Estrin C, Carothers DJ, Pepin RA, Javed AA, Jesse BW, Ganapathi MK, Samols D, Patel MS: Cloning and cDNA sequence of the dihydrolipoamide dehydrogenase component human alpha-ketoacid dehydrogenase complexes. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1422-6. doi: 10.1073/pnas.85.5.1422.
Pubmed: 3278312
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