Dihydrolipoamide dehydrogenase
Dihydrolipoamide dehydrogenase (DLD), also known as dihydrolipoyl dehydrogenase, mitochondrial, is an enzyme that in humans is encoded by the DLD gene.[1][2][3][4] DLD is a flavoprotein enzyme that degrades lipoamide, and produces dihydrolipoamide.
Function
This gene encodes the L protein of the mitochondrial glycine cleavage system. The L protein, also named dihydrolipoamide dehydrogenase, is also a component of the pyruvate dehydrogenase complex, the alpha-ketoglutarate dehydrogenase complex, and the branched-chain alpha-keto acide dehydrogenase complex.[1]
Clinical significance
Mutations in this gene have been identified in patients with E3-deficient maple syrup urine disease and lipoamide dehydrogenase deficiency.[1]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[5]
See also
References
- ^ a b c "Entrez Gene: dihydrolipoamide dehydrogenase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1738.
- ^ Otulakowski G, Robinson BH (December 1987). "Isolation and sequence determination of cDNA clones for porcine and human lipoamide dehydrogenase. Homology to other disulfide oxidoreductases". J. Biol. Chem. 262 (36): 17313–8. PMID 3693355.
- ^ Pons G, Raefsky-Estrin C, Carothers DJ, Pepin RA, Javed AA, Jesse BW, Ganapathi MK, Samols D, Patel MS (March 1988). "Cloning and cDNA sequence of the dihydrolipoamide dehydrogenase component human alpha-ketoacid dehydrogenase complexes". Proc. Natl. Acad. Sci. U.S.A. 85 (5): 1422–6. doi:10.1073/pnas.85.5.1422. PMC 279783. PMID 3278312. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=279783.
- ^ Scherer SW, Otulakowski G, Robinson BH, Tsui LC (1991). "Localization of the human dihydrolipoamide dehydrogenase gene (DLD) to 7q31----q32". Cytogenet. Cell Genet. 56 (3-4): 176–7. PMID 2055113.
- ^ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78". http://www.wikipathways.org/index.php/Pathway:WP78.
Further reading
- Silverberg MS, Cho JH, Rioux JD, et al. (2009). "Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.". Nat. Genet. 41 (2): 216–20. doi:10.1038/ng.275. PMC 2652837. PMID 19122664. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2652837.
- Scherer SW, Cheung J, MacDonald JR, et al. (2003). "Human chromosome 7: DNA sequence and biology.". Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2882961.
- Brautigam CA, Chuang JL, Tomchick DR, et al. (2005). "Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations.". J. Mol. Biol. 350 (3): 543–52. doi:10.1016/j.jmb.2005.05.014. PMID 15946682.
- , Barrett JC, Lee JC, et al. (2009). "Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region.". Nat. Genet. 41 (12): 1330–4. doi:10.1038/ng.483. PMID 19915572.
- Reed LJ, Hackert ML (1990). "Structure-function relationships in dihydrolipoamide acyltransferases.". J. Biol. Chem. 265 (16): 8971–4. PMID 2188967.
- Ciszak EM, Makal A, Hong YS, et al. (2006). "How dihydrolipoamide dehydrogenase-binding protein binds dihydrolipoamide dehydrogenase in the human pyruvate dehydrogenase complex.". J. Biol. Chem. 281 (1): 648–55. doi:10.1074/jbc.M507850200. PMID 16263718.
- Asano K, Matsushita T, Umeno J, et al. (2009). "A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population.". Nat. Genet. 41 (12): 1325–9. doi:10.1038/ng.482. PMID 19915573.
- Odièvre MH, Chretien D, Munnich A, et al. (2005). "A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency.". Hum. Mutat. 25 (3): 323–4. doi:10.1002/humu.9319. PMID 15712224.
- Brautigam CA, Wynn RM, Chuang JL, et al. (2006). "Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex.". Structure 14 (3): 611–21. doi:10.1016/j.str.2006.01.001. PMID 16442803.
- Kim H (2006). "Activity of human dihydrolipoamide dehydrogenase is largely reduced by mutation at isoleucine-51 to alanine.". J. Biochem. Mol. Biol. 39 (2): 223–7. PMID 16584639.
- Sugden MC, Holness MJ (2003). "Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs.". Am. J. Physiol. Endocrinol. Metab. 284 (5): E855-62. doi:10.1152/ajpendo.00526.2002. PMID 12676647.
- Wang YC, Wang ST, Li C, et al. (2008). "The role of amino acids T148 and R281 in human dihydrolipoamide dehydrogenase.". J. Biomed. Sci. 15 (1): 37–46. doi:10.1007/s11373-007-9208-9. PMID 17960497.
- Brown AM, Gordon D, Lee H, et al. (2004). "Association of the dihydrolipoamide dehydrogenase gene with Alzheimer's disease in an Ashkenazi Jewish population.". Am. J. Med. Genet. B Neuropsychiatr. Genet. 131B (1): 60–6. doi:10.1002/ajmg.b.30008. PMID 15389771.
- Babady NE, Pang YP, Elpeleg O, Isaya G (2007). "Cryptic proteolytic activity of dihydrolipoamide dehydrogenase.". Proc. Natl. Acad. Sci. U.S.A. 104 (15): 6158–63. doi:10.1073/pnas.0610618104. PMID 17404228.
- Wang YC, Wang ST, Li C, et al. (2007). "The role of N286 and D320 in the reaction mechanism of human dihydrolipoamide dehydrogenase (E3) center domain.". J. Biomed. Sci. 14 (2): 203–10. doi:10.1007/s11373-006-9136-0. PMID 17171578.
- Foster LJ, Rudich A, Talior I, et al. (2006). "Insulin-dependent interactions of proteins with GLUT4 revealed through stable isotope labeling by amino acids in cell culture (SILAC).". J. Proteome Res. 5 (1): 64–75. doi:10.1021/pr0502626. PMID 16396496.
- Kim H (2005). "Asparagine-473 residue is important to the efficient function of human dihydrolipoamide dehydrogenase.". J. Biochem. Mol. Biol. 38 (2): 248–52. PMID 15826505.
- Hiromasa Y, Fujisawa T, Aso Y, Roche TE (2004). "Organization of the cores of the mammalian pyruvate dehydrogenase complex formed by E2 and E2 plus the E3-binding protein and their capacities to bind the E1 and E3 components.". J. Biol. Chem. 279 (8): 6921–33. doi:10.1074/jbc.M308172200. PMID 14638692.
- Wynn RM, Kato M, Machius M, et al. (2004). "Molecular mechanism for regulation of the human mitochondrial branched-chain alpha-ketoacid dehydrogenase complex by phosphorylation.". Structure 12 (12): 2185–96. doi:10.1016/j.str.2004.09.013. PMID 15576032.
- Martins-de-Souza D, Gattaz WF, Schmitt A, et al. (2009). "Proteome analysis of schizophrenia patients Wernicke's area reveals an energy metabolism dysregulation.". BMC Psychiatry 9: 17. doi:10.1186/1471-244X-9-17. PMC 2684104. PMID 19405953. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2684104.
External links
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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PDB gallery
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1zy8: The crystal structure of dihydrolipoamide dehydrogenase and dihydrolipoamide dehydrogenase-binding protein (didomain) subcomplex of human pyruvate dehydrogenase complex.
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2f5z: Crystal Structure of Human Dihydrolipoamide Dehydrogenase (E3) Complexed to the E3-Binding Domain of Human E3-Binding Protein
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1zmc: Crystal Structure of Human dihydrolipoamide dehydrogenase complexed to NAD+
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1zmd: Crystal Structure of Human dihydrolipoamide dehydrogenase complexed to NADH
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| 1.8.1: NAD or NADP |
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| 1.8.2: cytochrome |
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| 1.8.3: oxygen |
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| 1.8.4: disulfide |
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| 1.8.5: quinone |
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| 1.8.98: Other, known |
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| 1.8.99: Other |
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B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m(A16/C10),i(k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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