ALAD

アミノレブリン酸デヒドラターゼ 5-aminolevulinic acid dehydratase

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/08 09:48:21」(JST)

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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 • 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
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: 116.15 – 116.16 Mb	Chr 4: 62.51 – 62.52 Mb
PubMed search	[1]	[2]

Delta-aminolevulinic acid dehydratase is an enzyme that in humans is encoded by the ALAD gene.

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.

References

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. 

UpToDate Contents

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English Journal

• Toxicity of Pb-contaminated soil to Japanese quail (Coturnix japonica) and the use of the blood-dietary Pb slope in risk assessment.

• Beyer WN, Chen Y, Henry P, May T, Mosby D, Rattner BA, Shearn-Bochsler VI, Sprague D, Weber J.Author information US Geological Survey, Patuxent Wildlife Research Center, Beltsville, Maryland, USA.AbstractThis study relates tissue concentrations and toxic effects of Pb in Japanese quail (Coturnix japonica) to the dietary exposure of soil-borne Pb associated with mining and smelting. From 0% to 12% contaminated soil, by weight, was added to 5 experimental diets (0.12 to 382 mg Pb/kg, dry wt) and fed to the quail for 6 weeks. Benchmark doses associated with a 50% reduction in delta-aminolevulinic acid dehydratase activity were 0.62 mg Pb/kg in the blood, dry wt, and 27 mg Pb/kg in the diet. Benchmark doses associated with a 20% increase in the concentration of erythrocyte protoporphyrin were 2.7 mg Pb/kg in the blood and 152 mg Pb/kg in the diet. The quail showed no other signs of toxicity (histopathological lesions, alterations in plasma-testosterone concentration, and body and organ weights). The relation of the blood Pb concentration to the soil Pb concentration was linear, with a slope of 0.013 mg Pb/kg of blood (dry wt) divided by mg Pb/kg of diet. We suggest that this slope is potentially useful in ecological risk assessments on birds in the same way that the intake slope factor is an important parameter in risk assessments of children exposed to Pb. The slope may also be used in a tissue-residue approach as an additional line of evidence in ecological risk assessment, supplementary to an estimate of hazard based on dietary toxicity reference values. Integr Environ Assess Manag 2014;10:22-29. © 2013 SETAC.
• Integrated environmental assessment and management.Integr Environ Assess Manag.2014 Jan;10(1):22-9. doi: 10.1002/ieam.1453. Epub 2013 Nov 21.
• This study relates tissue concentrations and toxic effects of Pb in Japanese quail (Coturnix japonica) to the dietary exposure of soil-borne Pb associated with mining and smelting. From 0% to 12% contaminated soil, by weight, was added to 5 experimental diets (0.12 to 382 mg Pb/kg, dry wt) and fed
• PMID 23780874

• Clinical perspective on oxidative stress in sporadic amyotrophic lateral sclerosis.

• D'Amico E, Factor-Litvak P, Santella RM, Mitsumoto H.Author information Eleanor and Lou Gehrig MDA/ALS Research Center, The Neurological Institute of New York, Columbia University Medical Center, New York, NY 10032, USA.AbstractSporadic amyotrophic lateral sclerosis (ALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the pro-oxidative/antioxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies in ALS indicate that oxidative stress plays a major role in motor neuron degeneration and astrocyte dysfunction. Oxidative stress biomarkers in cerebrospinal fluid, plasma, and urine are elevated, suggesting that abnormal oxidative stress is generated outside of the central nervous system. Our review indicates that agricultural chemicals, heavy metals, military service, professional sports, excessive physical exertion, chronic head trauma, and certain foods might be modestly associated with ALS risk, with a stronger association between risk and smoking. At the cellular level, these factors are all involved in generating oxidative stress. Experimental studies indicate that a combination of insults that induce modest oxidative stress can exert additive deleterious effects on motor neurons, suggesting that multiple exposures in real-world environments are important. As the disease progresses, nutritional deficiency, cachexia, psychological stress, and impending respiratory failure may further increase oxidative stress. Moreover, accumulating evidence suggests that ALS is possibly a systemic disease. Laboratory, pathologic, and epidemiologic evidence clearly supports the hypothesis that oxidative stress is central in the pathogenic process, particularly in genetically susceptive individuals. If we are to improve ALS treatment, well-designed biochemical and genetic epidemiological studies, combined with a multidisciplinary research approach, are needed and will provide knowledge crucial to our understanding of ALS etiology, pathophysiology, and prognosis.
• Free radical biology & medicine.Free Radic Biol Med.2013 Dec;65:509-27. doi: 10.1016/j.freeradbiomed.2013.06.029. Epub 2013 Jun 21.
• Sporadic amyotrophic lateral sclerosis (ALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the pro-oxidative/antioxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies
• PMID 23797033

• In vitro glutathione peroxidase mimicry of ebselen is linked to its oxidation of critical thiols on key cerebral suphydryl proteins - A novel component of its GPx-mimic antioxidant mechanism emerging from its thiol-modulated toxicology and pharmacology.

• Kade IJ, Balogun BD, Rocha JB.Author information Department of Biochemistry, Federal University of Technology, Akure, Ondo State, Nigeria. Electronic address: ijkade@yahoo.com.AbstractThe antioxidant mechanism of ebselen in rats brain is largely linked with its glutathione peroxidase (GPx) rather than its peroxiredoxin mimicry ability. However, the precise molecular dynamics between the GPx-mimicry of ebselen and thiol utilization is yet to be fully clarified and thus still open. Herein, we investigated the influence of dithiothreitol (DTT) on the antioxidant action of ebselen against oxidant-induced cerebral lipid peroxidation and deoxyribose degradation. Furthermore, the critical inhibitory concentrations of ebselen on the activities of sulphydryl enzymes such as cerebral sodium pump, δ-aminolevulinic acid dehydratase (δ-ALAD) and lactate dehydrogenase (LDH) were also investigated. We observe that ebselen (at ≥42 μM) markedly inhibited lipid peroxidation in the presence and absence of DTT, whereas it inhibited deoxyribose degradation only in the presence of DTT. Furthermore, under in vitro conditions, ebselen inhibited the thiol containing enzymes; cerebral sodium pump (at ≥40 μM), δ-ALAD (≥10 μM) and LDH (≥1 μM) which were either prevented or reversed by DTT. However, the inhibition of the activities of these sulphydryl proteins in diabetic animals was prevented by ebselen. Summarily, it is apparent that the effective in vitro inhibitory doses of ebselen on the activity of the sulphydryl proteins are far less than its antioxidant doses. In addition, the presence of DTT is evidently a critical requirement for ebselen to effect its antioxidant action against deoxyribose degeradation and not lipid peroxidation. Consequently, we conclude that ebselen possibly utilizes available thiols on sulphydryl proteins to effect its GPx mimicry antioxidant action against lipid peroxidation in rat brain homogenate.
• Chemico-biological interactions.Chem Biol Interact.2013 Oct 25;206(1):27-36. doi: 10.1016/j.cbi.2013.07.014. Epub 2013 Aug 7.
• The antioxidant mechanism of ebselen in rats brain is largely linked with its glutathione peroxidase (GPx) rather than its peroxiredoxin mimicry ability. However, the precise molecular dynamics between the GPx-mimicry of ebselen and thiol utilization is yet to be fully clarified and thus still open.
• PMID 23933410

Japanese Journal

• Effect of cadmium binding form on rabbit aminolevulinate dehydratase in high molecular weight fraction of rainbow trout liver

• JIA Huijuan,REN Huifeng,ENDO Hideaki,HAYASHI Tetsuhito
• Fisheries science : FS 76(3), 495-501, 2010-05-01
• NAID 10026450096

• 色素関係 δ-アミノレブリン酸脱水酵素(ALAD) (広範囲 血液・尿化学検査,免疫学的検査(第7版・1)その数値をどう読むか) -- (生化学的検査(1))

• 田島 裕
• 日本臨床 67(-) (968), 784-786, 2009-12
• NAID 40016874614

• Influence of Precursors and Inhibitor on the Production of Extracellular 5-Aminolevulinic Acid and Biomass by Rhodopseudomonas palustric KG31

• SAIKEUR Angkana,CHOORIT Wanna,PRASERTSAN Poonsuk,KANTACHOTE Duangporn,SASAKI Ken
• Bioscience, biotechnology, and biochemistry 73(5), 987-992, 2009-05-23
• … In this work, the effects of two precursors and an inhibitor of aminolevulinic dehydratase (ALAD) added to the VFA culture medium on the production of ALA and biomass were investigated. …
• NAID 10027540426

Related Links

• ALAD'ORO / GOODNESS SPORTS LABORATORY

埼玉県熊谷市を中心とするサッカースクール ... やる気のある子は全員のばす。変える。 ALAD'OROでは選抜やセレクションは一切していません。 なので、入団条件はすごくシンプル。

• δ-アミノレブリン酸脱水酵素｜シスメックス プライマリケア

ALADは8つのヘム合成系酵素の中で最も量が多く，赤血球ALAD活性（-DTTまたは＋DTT）が正常の90％以上減少してもポルフィリンの代謝異常は通常みられない．また，ALAD活性は各種治療薬や生体内外のさまざまな因子によっても影響を ...

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★リンクテーブル★

リンク元	「アミノレブリン酸デヒドラターゼ」
拡張検索	「ALAD deficiency」
関連記事	「AL」「ALA」

「アミノレブリン酸デヒドラターゼ」

　　[★]

dehydratase

英

aminolevulinate dehydratase, aminolevulinic acid dehydratase, 5-aminolevulinate dehydratase, 5-aminolevulinic acid dehydratase, ALAD, ALA-D

関

ヘム

「ALAD deficiency」

　　[★]

同

5-aminolevulinic acid dehydratase

「AL」

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• アルギニノコハク酸リアーゼ argininosuccinate lyase
• 急性白血病 acute leukemia
• アミロイドL鎖蛋白質 amyloid light chain protein

　

「ALA」

　　[★] 5-アミノレブリン酸 5-aminolevulinate