5-amminolevulinato deidratasi

La 5-amminolevulinato deidratasi (porfobilinogeno sintasi) è un enzima citosolico che catalizza la reazione tra due molecole di acido 5-aminolevulinico per formare porfobilinogeno, il che rappresenta la seconda tappa del processo biosintetico dell'eme. È una proteina con peso di 280 KDa costituita da otto subunità, di cui quattro interagiscono con l'acido 5-aminolevulinico. L'ALA deidratasi è un enzima zinco-dipendente. È inibito da molti metalli pesanti e particolarmente dal piombo, ed infatti, in caso di avvelenamento da piombo, l'acido 5-aminolevulinico si accumula nell'organismo senza essere trasformato in porfobilinogeno proprio a causa dell'inibizione di questo enzima.

5-amminolevulinato deidratasi
Modello tridimensionale dell'enzima
Numero EC	4.2.1.24
Classe	Liasi
Banche dati	BRENDA, EXPASY, GTD, PDB (RCSB PDB PDBe PDBj PDBsum)
Fonte: IUBMB

Bibliografia

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• Plewinska M, Thunell S, Holmberg L, et al., delta-Aminolevulinate dehydratase deficient porphyria: identification of the molecular lesions in a severely affected homozygote, in Am. J. Hum. Genet., vol. 49, n. 1, 1991, pp. 167–74, PMC 1683193, PMID 2063868.
• Potluri VR, Astrin KH, Wetmur JG, et al., Human delta-aminolevulinate dehydratase: chromosomal localization to 9q34 by in situ hybridization, in Hum. Genet., vol. 76, n. 3, 1987, pp. 236–9, DOI:10.1007/BF00283614, PMID 3036687.
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• Wetmur JG, Bishop DF, Cantelmo C, Desnick RJ, Human delta-aminolevulinate dehydratase: nucleotide sequence of a full-length cDNA clone, in Proc. Natl. Acad. Sci. U.S.A., vol. 83, n. 20, 1986, pp. 7703–7, DOI:10.1073/pnas.83.20.7703, PMC 386789, PMID 3463993.
• Wetmur JG, Bishop DF, Ostasiewicz L, Desnick RJ, Molecular cloning of a cDNA for human delta-aminolevulinate dehydratase, in Gene, vol. 43, n. 1-2, 1986, pp. 123–30, DOI:10.1016/0378-1119(86)90015-6, PMID 3758678.
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• Kaya AH, Plewinska M, Wong DM, et al., Human delta-aminolevulinate dehydratase (ALAD) gene: structure and alternative splicing of the erythroid and housekeeping mRNAs, in Genomics, vol. 19, n. 2, 1994, pp. 242–8, DOI:10.1006/geno.1994.1054, PMID 8188255.
• Akagi R, Yasui Y, Harper P, Sassa S, A novel mutation of delta-aminolaevulinate dehydratase in a healthy child with 12% erythrocyte enzyme activity, in Br. J. Haematol., vol. 106, n. 4, 1999, pp. 931–7, DOI:10.1046/j.1365-2141.1999.01647.x, PMID 10519994.
• Akagi R, Shimizu R, Furuyama K, et al., Novel molecular defects of the delta-aminolevulinate dehydratase gene in a patient with inherited acute hepatic porphyria, in Hepatology, vol. 31, n. 3, 2000, pp. 704–8, DOI:10.1002/hep.510310321, PMID 10706561.
• Kervinen J, Jaffe EK, Stauffer F, et al., Mechanistic basis for suicide inactivation of porphobilinogen synthase by 4,7-dioxosebacic acid, an inhibitor that shows dramatic species selectivity, in Biochemistry, vol. 40, n. 28, 2001, pp. 8227–36, DOI:10.1021/bi010656k, PMID 11444968.

Voci correlate

• 5-amminolevulinato sintasi
• Eme
• Piombo

Collegamenti esterni

• (EN) ALAD, su Enciclopedia Britannica, Encyclopædia Britannica, Inc.

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