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Pathway Description
Lactic Acidemia
Homo sapiens
Disease Pathway
Created: 2013-08-01
Last Updated: 2022-12-07
Increased lactic acid concentrations in urine or serum can be a result of many metabolic disorders but also of other origin (infections, etc.). Respiratory chain defects account for most of the metabolic causes of lactic acid accumulation. Often alanine is also high. A urine spectrum indicating an increased lactic acid and alanine concentration is shown.
References
Lactic Acidemia References
[OMIM: Entry 312170](http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=312170)
[Uniprot: P08559](http://www.uniprot.org/uniprot/P08559)
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.60 Heilbronn: SPS Verlagsgesellschaft
Birch-Machin MA, Shepherd IM, Solomon M, Yeaman SJ, Gardner-Medwin D, Sherratt HS, Lindsay JG, Aynsley-Green A, Turnbull DM: Fatal lactic acidosis due to deficiency of E1 component of the pyruvate dehydrogenase complex. J Inherit Metab Dis. 1988;11(2):207-17.
Pubmed: 3139934
Blass JP, Kark AP, Engel WK: Clinical studies of a patient with pyruvate decarboxylase deficiency. Arch Neurol. 1971 Nov;25(5):449-60.
Pubmed: 5110887
Brown GK, Otero LJ, LeGris M, Brown RM: Pyruvate dehydrogenase deficiency. J Med Genet. 1994 Nov;31(11):875-9.
Pubmed: 7853374
Brown RM, Head RA, Boubriak II, Leonard JV, Thomas NH, Brown GK: Mutations in the gene for the E1beta subunit: a novel cause of pyruvate dehydrogenase deficiency. Hum Genet. 2004 Jul;115(2):123-7. doi: 10.1007/s00439-004-1124-8. Epub 2004 May 11.
Pubmed: 15138885
Brown RM, Dahl HH, Brown GK: X-chromosome localization of the functional gene for the E1 alpha subunit of the human pyruvate dehydrogenase complex. Genomics. 1989 Feb;4(2):174-81.
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Dahl HH, Brown GK, Brown RM, Hansen LL, Kerr DS, Wexler ID, Patel MS, De Meirleir L, Lissens W, Chun K, et al.: Mutations and polymorphisms in the pyruvate dehydrogenase E1 alpha gene. Hum Mutat. 1992;1(2):97-102. doi: 10.1002/humu.1380010203.
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Pubmed: 9686362
Robinson BH: Lactic acidemia and mitochondrial disease. Mol Genet Metab. 2006 Sep-Oct;89(1-2):3-13. doi: 10.1016/j.ymgme.2006.05.015. Epub 2006 Jul 18.
Pubmed: 16854608
Alanine Metabolism 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.
MacDonald M, Neufeldt N, Park BN, Berger M, Ruderman N: Alanine metabolism and gluconeogenesis in the rat. Am J Physiol. 1976 Aug;231(2):619-26. doi: 10.1152/ajplegacy.1976.231.2.619.
Pubmed: 961915
Ruderman NB, Schmahl FW, Goodman MN: Regulation of alanine formation and release in rat muscle in vivo: effect of starvation and diabetes. Am J Physiol. 1977 Aug;233(2):E109-14. doi: 10.1152/ajpendo.1977.233.2.E109.
Pubmed: 888947
Garber AJ, Karl IE, Kipnis DM: Alanine and glutamine synthesis and release from skeletal muscle. I. Glycolysis and amino acid release. J Biol Chem. 1976 Feb 10;251(3):826-35.
Pubmed: 1249058
Garber AJ, Karl IE, Kipnis DM: Alanine and glutamine synthesis and release from skeletal muscle. II. The precursor role of amino acids in alanine and glutamine synthesis. J Biol Chem. 1976 Feb 10;251(3):836-43.
Pubmed: 1249059
Shiba K, Ripmaster T, Suzuki N, Nichols R, Plotz P, Noda T, Schimmel P: Human alanyl-tRNA synthetase: conservation in evolution of catalytic core and microhelix recognition. Biochemistry. 1995 Aug 22;34(33):10340-9. doi: 10.1021/bi00033a004.
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Pubmed: 14702039
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Pubmed: 15616553
Sohocki MM, Sullivan LS, Harrison WR, Sodergren EJ, Elder FF, Weinstock G, Tanase S, Daiger SP: Human glutamate pyruvate transaminase (GPT): localization to 8q24.3, cDNA and genomic sequences, and polymorphic sites. Genomics. 1997 Mar 1;40(2):247-52. doi: 10.1006/geno.1996.4604.
Pubmed: 9119391
Ishiguro M, Takio K, Suzuki M, Oyama R, Matsuzawa T, Titani K: Complete amino acid sequence of human liver cytosolic alanine aminotransferase (GPT) determined by a combination of conventional and mass spectral methods. Biochemistry. 1991 Oct 29;30(43):10451-7. doi: 10.1021/bi00107a013.
Pubmed: 1931970
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Pubmed: 15489334
Wexler ID, Du Y, Lisgaris MV, Mandal SK, Freytag SO, Yang BS, Liu TC, Kwon M, Patel MS, Kerr DS: Primary amino acid sequence and structure of human pyruvate carboxylase. Biochim Biophys Acta. 1994 Oct 21;1227(1-2):46-52. doi: 10.1016/0925-4439(94)90105-8.
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MacKay N, Rigat B, Douglas C, Chen HS, Robinson BH: cDNA cloning of human kidney pyruvate carboxylase. Biochem Biophys Res Commun. 1994 Jul 29;202(2):1009-14. doi: 10.1006/bbrc.1994.2029.
Pubmed: 8048912
von Schnakenburg C, Rumsby G: Primary hyperoxaluria type 1: a cluster of new mutations in exon 7 of the AGXT gene. J Med Genet. 1997 Jun;34(6):489-92. doi: 10.1136/jmg.34.6.489.
Pubmed: 9192270
Basmaison O, Rolland MO, Cochat P, Bozon D: Identification of 5 novel mutations in the AGXT gene. Hum Mutat. 2000 Jun;15(6):577. doi: 10.1002/1098-1004(200006)15:6<577::AID-HUMU9>3.0.CO;2-#.
Pubmed: 10862087
Nishiyama K, Berstein G, Oda T, Ichiyama A: Cloning and nucleotide sequence of cDNA encoding human liver serine-pyruvate aminotransferase. Eur J Biochem. 1990 Nov 26;194(1):9-18. doi: 10.1111/j.1432-1033.1990.tb19420.x.
Pubmed: 2253628
Dallabona C, Diodato D, Kevelam SH, Haack TB, Wong LJ, Salomons GS, Baruffini E, Melchionda L, Mariotti C, Strom TM, Meitinger T, Prokisch H, Chapman K, Colley A, Rocha H, Ounap K, Schiffmann R, Salsano E, Savoiardo M, Hamilton EM, Abbink TE, Wolf NI, Ferrero I, Lamperti C, Zeviani M, Vanderver A, Ghezzi D, van der Knaap MS: Novel (ovario) leukodystrophy related to AARS2 mutations. Neurology. 2014 Jun 10;82(23):2063-71. doi: 10.1212/WNL.0000000000000497. Epub 2014 May 7.
Pubmed: 24808023
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Pubmed: 10574462
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Pubmed: 10810093
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