ALAD

Aminolevulinate dehydratase

PDB rendering based on 1e51.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1E51, 1PV8

Identifiers

Symbols

ALAD ; ALADH; PBGS

External IDs

OMIM: 125270 MGI: 96853 HomoloGene: 16 ChEMBL: 3126 GeneCards: ALAD Gene

EC number

4.2.1.24

Gene ontology
Molecular function	• catalytic activity • porphobilinogen synthase activity • zinc ion binding • lead ion binding • identical protein binding
Cellular component	• nucleus • cytosol • extracellular vesicular exosome
Biological process	• porphyrin-containing compound metabolic process • protoporphyrinogen IX biosynthetic process • heme biosynthetic process • small molecule metabolic process • protein homooligomerization • cellular response to interleukin-4
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 9:
116.15 – 116.16 Mb

Chr 4:
62.51 – 62.52 Mb

PubMed search

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".

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. doi:10.1136/oem.32.3.181. PMC 1008057. PMID 1156566.
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.
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.
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.
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.
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.
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.
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.

PDB gallery

1e51: CRYSTAL STRUCTURE OF NATIVE HUMAN ERYTHROCYTE 5-AMINOLAEVULINIC ACID DEHYDRATASE

1pv8: Crystal structure of a low activity F12L mutant of human phorphobilinogen synthase

ALAD

References

Further reading