ALAD
Delta-aminolevulinic acid dehydratase is an enzyme that in humans is encoded by the ALAD gene.[1][2]
The ALAD enzyme is composed of 8 identical subunits and catalyzes the condensation of 2 molecules of delta-aminolevulinate to form porphobilinogen (a precursor of heme, cytochromes and other hemoproteins). ALAD catalyzes the second step in the porphyrin and heme biosynthetic pathway; zinc is essential for enzymatic activity. ALAD enzymatic activity is inhibited by lead and a defect in the ALAD structural gene can cause increased sensitivity to lead poisoning and acute hepatic porphyria. Alternatively spliced transcript variants encoding different isoforms have been identified.[3]
References
- ^ Eiberg H, Mohr J, Nielsen LS (Jun 1983). "delta-Aminolevulinatedehydrase: synteny with ABO-AK1-ORM (and assignment to chromosome 9)". Clin Genet 23 (2): 150–4. doi:10.1111/j.1399-0004.1983.tb01864.x. PMID 6839527.
- ^ Beaumont C, Foubert C, Grandchamp B, Weil D, Van Cong N'Guyen, Gross MS, Nordmann Y (Aug 1984). "Assignment of the human gene for delta aminolevulinate dehydrase to chromosome 9 by somatic cell hybridization and specific enzyme immunoassay". Ann Hum Genet 48 (Pt 2): 153–9. doi:10.1111/j.1469-1809.1984.tb01010.x. PMID 6378062.
- ^ "Entrez Gene: ALAD aminolevulinate, delta-, dehydratase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=210.
Further reading
- Bernard A, Lauwerys R (1988). "Metal-induced alterations of delta-aminolevulinic acid dehydratase.". Ann. N. Y. Acad. Sci. 514: 41–7. doi:10.1111/j.1749-6632.1987.tb48759.x. PMID 3327436.
- Jaffe EK (2005). "The porphobilinogen synthase catalyzed reaction mechanism.". Bioorg. Chem. 32 (5): 316–25. doi:10.1016/j.bioorg.2004.05.010. PMID 15381398.
- Roels HA, Buchet JP, Lauwerys RR, Sonnet J (1975). "Comparison of in vivo effect of inorganic lead and cadmium on glutathione reductase system and delta-aminolevulinate dehydratase in human erythrocytes.". British journal of industrial medicine 32 (3): 181–92. PMC 1008057. PMID 1156566. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1008057.
- Ishida N, Fujita H, Fukuda Y, et al. (1992). "Cloning and expression of the defective genes from a patient with delta-aminolevulinate dehydratase porphyria.". J. Clin. Invest. 89 (5): 1431–7. doi:10.1172/JCI115732. PMC 443012. PMID 1569184. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=443012.
- Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin.". J. Infect. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151.
- Astrin KH, Kaya AH, Wetmur JG, Desnick RJ (1991). "RsaI polymorphism in the human delta-aminolevulinate dehydratase gene at 9q34.". Nucleic Acids Res. 19 (15): 4307. doi:10.1093/nar/19.15.4307-a. PMC 328595. PMID 1678509. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=328595.
- Wetmur JG, Kaya AH, Plewinska M, Desnick RJ (1991). "Molecular characterization of the human delta-aminolevulinate dehydratase 2 (ALAD2) allele: implications for molecular screening of individuals for genetic susceptibility to lead poisoning.". Am. J. Hum. Genet. 49 (4): 757–63. PMC 1683158. PMID 1716854. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1683158.
- Plewinska M, Thunell S, Holmberg L, et al. (1991). "delta-Aminolevulinate dehydratase deficient porphyria: identification of the molecular lesions in a severely affected homozygote.". Am. J. Hum. Genet. 49 (1): 167–74. PMC 1683193. PMID 2063868. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1683193.
- Potluri VR, Astrin KH, Wetmur JG, et al. (1987). "Human delta-aminolevulinate dehydratase: chromosomal localization to 9q34 by in situ hybridization.". Hum. Genet. 76 (3): 236–9. doi:10.1007/BF00283614. PMID 3036687.
- Gibbs PN, Jordan PM (1986). "Identification of lysine at the active site of human 5-aminolaevulinate dehydratase.". Biochem. J. 236 (2): 447–51. PMC 1146860. PMID 3092810. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1146860.
- Wetmur JG, Bishop DF, Cantelmo C, Desnick RJ (1986). "Human delta-aminolevulinate dehydratase: nucleotide sequence of a full-length cDNA clone.". Proc. Natl. Acad. Sci. U.S.A. 83 (20): 7703–7. doi:10.1073/pnas.83.20.7703. PMC 386789. PMID 3463993. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=386789.
- Wetmur JG, Bishop DF, Ostasiewicz L, Desnick RJ (1986). "Molecular cloning of a cDNA for human delta-aminolevulinate dehydratase.". Gene 43 (1-2): 123–30. doi:10.1016/0378-1119(86)90015-6. PMID 3758678.
- Doss M, von Tiepermann R, Schneider J (1981). "Acute hepatic porphyria syndrome with porphobilinogen synthase defect.". Int. J. Biochem. 12 (5-6): 823–6. doi:10.1016/0020-711X(80)90170-6. PMID 7450139.
- Kaya AH, Plewinska M, Wong DM, et al. (1994). "Human delta-aminolevulinate dehydratase (ALAD) gene: structure and alternative splicing of the erythroid and housekeeping mRNAs.". Genomics 19 (2): 242–8. doi:10.1006/geno.1994.1054. PMID 8188255.
- Akagi R, Yasui Y, Harper P, Sassa S (1999). "A novel mutation of delta-aminolaevulinate dehydratase in a healthy child with 12% erythrocyte enzyme activity.". Br. J. Haematol. 106 (4): 931–7. doi:10.1046/j.1365-2141.1999.01647.x. PMID 10519994.
- Akagi R, Shimizu R, Furuyama K, et al. (2000). "Novel molecular defects of the delta-aminolevulinate dehydratase gene in a patient with inherited acute hepatic porphyria.". Hepatology 31 (3): 704–8. doi:10.1002/hep.510310321. PMID 10706561.
- Kervinen J, Jaffe EK, Stauffer F, et al. (2001). "Mechanistic basis for suicide inactivation of porphobilinogen synthase by 4,7-dioxosebacic acid, an inhibitor that shows dramatic species selectivity.". Biochemistry 40 (28): 8227–36. doi:10.1021/bi010656k. PMID 11444968.
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PDB gallery
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1e51: CRYSTAL STRUCTURE OF NATIVE HUMAN ERYTHROCYTE 5-AMINOLAEVULINIC ACID DEHYDRATASE
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1pv8: Crystal structure of a low activity F12L mutant of human phorphobilinogen synthase
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