ALAD

Aminolevulinate dehydratase
PDB rendering based on 1e51.
Available structures PDB 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 • extracellular space • nucleus • cytosol • extracellular exosome Biological process • response to hypoxia • porphyrin-containing compound metabolic process • protoporphyrinogen IX biosynthetic process • heme biosynthetic process • response to oxidative stress • response to herbicide • response to iron ion • response to zinc ion • response to aluminum ion • response to ionizing radiation • response to vitamin B1 • response to selenium ion • response to activity • response to cobalt ion • response to lipopolysaccharide • response to vitamin E • response to drug • response to amino acid • small molecule metabolic process • response to ethanol • response to arsenic-containing substance • response to cadmium ion • response to mercury ion • protein homooligomerization • response to glucocorticoid • response to methylmercury • response to platinum ion • response to fatty acid • cellular response to lead ion • cellular response to interleukin-4 Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	210	17025
Ensembl	ENSG00000148218	ENSMUSG00000028393
UniProt	P13716	P10518
RefSeq (mRNA)	NM_000031	NM_001276446
RefSeq (protein)	NP_000022	NP_001263375
Location (UCSC)	Chr 9: 113.39 – 113.4 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, beginning at blood lead levels that were once considered to be safe (<10 μg/dL) and continuing to correlate negatively across the range from 5 to 95 μg/dL.^[3] Inhibition of ALAD by lead leads to anemia primarily because it both inhibits heme synthesis and shortens the lifespan of circulating red blood cells, but also by stimulating the excessive production of the hormone erythropoietin, leading to inadequate maturation of red cells from their progenitors. 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.^[4]

References

1. 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.
2. 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.
3. Abadin H, Ashizawa A, Stevens YW, Llados F, Diamond G, Sage G, Citra M, Quinones A, Bosch SJ, Swarts SG (August 2007). Toxicological Profile for Lead (PDF). Atlanta, GA: Agency for Toxic Substances and Disease Registry (US). pp. 22, 30. PMID 24049859. Retrieved 22 November 2015.
4. "Entrez Gene: ALAD aminolevulinate, delta-, dehydratase".

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. 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.