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Pathway Description
Pyruvate Dehydrogenase Deficiency (E2)
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-08-16
Pyruvate Dehydrogenase (PDH) Deficiency is an X linked disease where individuals have a reduced number of functioning PDH complexes ultimately affecting the mitochondria’s energy metabolism. In a healthy individual, PDH complex catalyzes the conversion of pyruvate to acetyl coenzyme A, therefore PDH deficiency can cause the accumulation of excess pyruvate and lactic acid. PDH deficiency presents itself in a variety of ways, however since the brain obtains most of it’s energy from aerobic oxidation of glucose, all PDH deficient individuals have some degree of neurological impairment. Other symptoms range from fatal lactic acidosis in the newborns, chronic neurodegenerative conditions, brain lesions, cerebral atrophy and much more.
Due to the fatal nature of the disease many with this condition do not live past childhood, however there are some that survive to adolescents and adulthood. Treatments have tried to minimize systemic lactic acid accumulation by feeding patients high fat/low carbohydrate diets. However, this does not reverse neurological structural damage already present and therefore does little to influence the end results.
References
Pyruvate Dehydrogenase Deficiency (E2) References
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Pubmed: 7853374
Citric Acid Cycle References
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Pubmed: 11708858
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Pubmed: 1581363
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Pubmed: 16141072
Ballif BA, Carey GR, Sunyaev SR, Gygi SP: Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain. J Proteome Res. 2008 Jan;7(1):311-8. doi: 10.1021/pr0701254. Epub 2007 Nov 23.
Pubmed: 18034455
Wang L, Kaneko S, Kagaya M, Ohno H, Honda M, Kobayashi K: Molecular cloning, and characterization and expression of dihydrolipoamide acetyltransferase component of murine pyruvate dehydrogenase complex in bile duct cancer cells. J Gastroenterol. 2002;37(6):449-54. doi: 10.1007/s005350200065.
Pubmed: 12108679
Johnson M, Yang HS, Johanning GL, Patel MS: Characterization of the mouse dihydrolipoamide dehydrogenase (Dld) gene: genomic structure, promoter sequence, and chromosomal localization. Genomics. 1997 May 1;41(3):320-6. doi: 10.1006/geno.1997.4670.
Pubmed: 9169128
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Pubmed: 21183079
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Pubmed: 9286695
Trinidad JC, Specht CG, Thalhammer A, Schoepfer R, Burlingame AL: Comprehensive identification of phosphorylation sites in postsynaptic density preparations. Mol Cell Proteomics. 2006 May;5(5):914-22. doi: 10.1074/mcp.T500041-MCP200. Epub 2006 Feb 1.
Pubmed: 16452087
Church DM, Goodstadt L, Hillier LW, Zody MC, Goldstein S, She X, Bult CJ, Agarwala R, Cherry JL, DiCuccio M, Hlavina W, Kapustin Y, Meric P, Maglott D, Birtle Z, Marques AC, Graves T, Zhou S, Teague B, Potamousis K, Churas C, Place M, Herschleb J, Runnheim R, Forrest D, Amos-Landgraf J, Schwartz DC, Cheng Z, Lindblad-Toh K, Eichler EE, Ponting CP: Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol. 2009 May 5;7(5):e1000112. doi: 10.1371/journal.pbio.1000112. Epub 2009 May 26.
Pubmed: 19468303
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 SMP0000551
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