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ALAD
Available structures
PDB	Pretraga ortologa: PDBe RCSB
List of PDB id codes
	1E51, 1PV8, 5HNR, 5HMS
Identifikatori
Alijasi	ALAD
Spoljašnji ID	OMIM: 125270 MGI: 96853 HomoloGene: 16 GeneCards: ALAD
Genska lokacija (miš)
Hr.	Chromosome 4 (mouse)
Kraj	62,438,155 bp
Obrazac RNK izražavanja
	; ;
	More reference expression data
Genska ontologija
Molecular function	• porphobilinogen synthase activity; • везивање јона цинка; • metal ion binding; • catalytic activity; • lyase activity; • identical protein binding; • proteasome core complex binding;
Cellular component	• цитосол; • extracellular exosome; • једро; • ванћелијска област; • ванћелијски простор; • 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; • реакција на хипоксију; • response to cadmium ion; • response to fatty acid; • response to vitamin B1; • GO:1904578 response to organic cyclic compound; • response to vitamin; • response to nutrient; • response to metal ion; • response to zinc ion; • одговор на глукокортикоидни подстицај; • response to arsenic-containing substance; • protoporphyrinogen IX biosynthetic process; • GO:0001306 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; • реакција на липополисахарид; • response to nutrient levels; • реакција на јоне олова; • response to inorganic substance; • response to aluminum ion; • response to hormone; • response to mercury ion; • метаболизам; • response to methylmercury; • реакција на етанол; • response to cobalt ion; • protein homooligomerization; • одговор на отровну супстанцу; • response to herbicide; • neutrophil degranulation; • negative regulation of proteasomal protein catabolic process;
	Sources:Amigo / QuickGO
Ortolozi
	210
	17025
	ENSG00000148218
	ENSMUSG00000028393
	P13716
	P10518
	NM_000031; NM_001003945; NM_001317745
	NM_001276446; NM_008525
	NP_000022; NP_001003945; NP_001304674
	NP_001263375; NP_032551
	Wikidata
View/Edit Human	View/Edit Mouse

Dehidrataza delta aminolevulinske kiseline je enzim koji je kod ljudi kodiran ALAD genom.^[4]^[5]

ALAD enzim se sastoji od 8 identičnih podjedinica i katalizuje kondenzaciju 2 molekula delta-aminolevulinata, čime se formira porfobilinogen (prekurzor hema, citohroma i drugih hemoproteina). ALAD katalizuje drugi korak u porfirinskom i hemnom biosintetičkom putu. Cink je esencijalan za enzimatsku aktivnost. Olovo inhibira ALAD, počevši od krvnih nivoa olova koji su nekad smatrani bezbednim (<10 μg/dL) i postoji negativna korelacija duž opseg od 5 do 95 μg/dL.^[6] Inhibicija ALAD-a olovom dovodi do anemije, prvenstveno zbog inhibicije sinteze hema i skraćivanja životnog veka cirkulišućih crvenih krvnih zrnaca, ali i zbog stimulisanja prekomerne produkcije hormona eritropoietina, što dovodi do neadekvatne maturacije crvenih krvnih zrnaca iz njihovih progenitora. Defekat u ALAD strukturnom genu može da dovede do povećane senzitivnosti na trovanje olovom i akutne hepatičke porfirije. Alternativno splajsovane transkriptne varijante koje kodiraju različite izoforme su identifikovane.^[7]

Vidi još

Porfobilinogenska sintaza, EC 4.2.1.24

Reference

^ ^а ^б ^в GRCm38: Ensembl release 89: ENSMUSG00000028393 - Ensembl, May 2017
^ „Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ „Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Eiberg H, Mohr J, Nielsen LS (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 (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 (2007). Toxicological Profile for Lead (PDF). Atlanta, GA: Agency for Toxic Substances and Disease Registry (US). стр. 22, 30. PMID 24049859. Приступљено 22. 11. 2015.
^ „Entrez Gene: ALAD aminolevulinate, delta-, dehydratase”.

Literatura

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.

[refGRCm38Ensembl-1] а ^б ^в GRCm38: Ensembl release 89: ENSMUSG00000028393 - Ensembl, May 2017

[2] „Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] „Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid6839527-4] Eiberg H, Mohr J, Nielsen LS (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.

[pmid6378062-5] Beaumont C; Foubert C; Grandchamp B; Weil D; Van Cong N'Guyen; Gross MS; Nordmann Y (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.

[ATSDR2007-6] Abadin H, Ashizawa A, Stevens YW, Llados F, Diamond G, Sage G, Citra M, Quinones A, Bosch SJ, Swarts SG (2007). Toxicological Profile for Lead (PDF). Atlanta, GA: Agency for Toxic Substances and Disease Registry (US). стр. 22, 30. PMID 24049859. Приступљено 22. 11. 2015.

[entrez-7] „Entrez Gene: ALAD aminolevulinate, delta-, dehydratase”.

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