Delta-aminolevulinic acid dehydratase

ALAD

Available structures

Ortholog search: PDBe RCSB

List of PDB id codes
1E51, 1PV8, 5HNR, 5HMS

Identifiers

Aliases

ALAD, ALADH, PBGS, aminolevulinate dehydratase

External IDs

MGI: 96853 HomoloGene: 16 GeneCards: ALAD

Gene ontology
Molecular function	• porphobilinogen synthase activity • zinc ion binding • metal ion binding • catalytic activity • lyase activity • identical protein binding • proteasome core complex binding
Cellular component	• cytosol • extracellular exosome • nucleus • extracellular region • extracellular space • secretory granule lumen • ficolin-1-rich granule lumen • proteasome core complex
Biological process	• cellular response to interleukin-4 • response to ionizing radiation • response to platinum ion • response to selenium ion • response to amino acid • cellular response to lead ion • response to hypoxia • response to cadmium ion • response to fatty acid • response to vitamin B1 • response to organic cyclic compound • response to vitamin • response to nutrient • response to metal ion • response to zinc ion • response to glucocorticoid • response to arsenic-containing substance • protoporphyrinogen IX biosynthetic process • response to oxidative stress • response to organic substance • response to activity • tetrapyrrole biosynthetic process • porphyrin-containing compound biosynthetic process • response to vitamin E • response to iron ion • heme biosynthetic process • response to lipopolysaccharide • response to nutrient levels • response to lead ion • response to inorganic substance • response to aluminum ion • response to hormone • response to mercury ion • metabolic process • response to methylmercury • response to ethanol • response to cobalt ion • protein homooligomerization • response to toxic substance • response to herbicide • response to drug • neutrophil degranulation • negative regulation of proteasomal protein catabolic process
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_001003945 NM_001317745


NM_001276446 NM_008525

RefSeq (protein)


NP_000022 NP_001003945 NP_001304674


NP_001263375 NP_032551

Location (UCSC)

Chr 9: 113.39 – 113.4 Mb

Chr 4: 62.51 – 62.52 Mb

PubMed search

^[1]

^[2]

Wikidata

View/Edit Human

View/Edit Mouse

Delta-aminolevulinic acid dehydratase is an enzyme (EC 4.2.1.24) that in humans is encoded by the ALAD gene.^[3]^[4] It catalyzes the following reaction:

2 δ-aminolevulinic acid

\rightleftharpoons

porphobilinogen + 2 H₂O

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.^[5] 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.^[6]

References

↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ 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. PMID 6839527. doi:10.1111/j.1399-0004.1983.tb01864.x.
↑ 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. PMID 6378062. doi:10.1111/j.1469-1809.1984.tb01010.x.
↑ 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.
↑ "Entrez Gene: ALAD aminolevulinate, delta-, dehydratase".

External links

Human ALAD genome location and ALAD gene details page in the UCSC Genome Browser.

Bernard A, Lauwerys R (1988). "Metal-induced alterations of delta-aminolevulinic acid dehydratase.". Ann. N. Y. Acad. Sci. 514: 41–7. PMID 3327436. doi:10.1111/j.1749-6632.1987.tb48759.x.
Jaffe EK (2005). "The porphobilinogen synthase catalyzed reaction mechanism.". Bioorg. Chem. 32 (5): 316–25. PMID 15381398. doi:10.1016/j.bioorg.2004.05.010.
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. doi:10.1136/oem.32.3.181.
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. PMC 443012 . PMID 1569184. doi:10.1172/JCI115732.
Dawson SJ, White LA (1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin.". J. Infect. 24 (3): 317–20. PMID 1602151. doi:10.1016/S0163-4453(05)80037-4.
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. PMC 328595 . PMID 1678509. doi:10.1093/nar/19.15.4307-a.
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. PMID 3036687. doi:10.1007/BF00283614.
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. PMC 386789 . PMID 3463993. doi:10.1073/pnas.83.20.7703.
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. PMID 3758678. doi:10.1016/0378-1119(86)90015-6.
Doss M, von Tiepermann R, Schneider J (1981). "Acute hepatic porphyria syndrome with porphobilinogen synthase defect.". Int. J. Biochem. 12 (5-6): 823–6. PMID 7450139. doi:10.1016/0020-711X(80)90170-6.
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. PMID 8188255. doi:10.1006/geno.1994.1054.
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. PMID 10519994. doi:10.1046/j.1365-2141.1999.01647.x.
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. PMID 10706561. doi:10.1002/hep.510310321.
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. PMID 11444968. doi:10.1021/bi010656k.

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

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Delta-aminolevulinic acid dehydratase

References

External links

Further reading