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MGP000110

UniProt Annotations

Entry Information
Gene Nameaminolevulinate dehydratase
Protein EntryHEM2_HUMAN
UniProt IDP13716
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=P13716-1; Sequence=Displayed; Name=2; IsoId=P13716-2; Sequence=VSP_037866;
Biophysicochemical PropertiesKinetic parameters: KM=0.09 mM for 5-aminolevulinate at pH 7 {ECO:0000269|PubMed:11032836}; Vmax=43 umol/h/mg enzyme at pH 7 {ECO:0000269|PubMed:11032836}; pH dependence: Optimum pH is 6.8-7.3. {ECO:0000269|PubMed:11032836};
Catalytic Activity2 5-aminolevulinate = porphobilinogen + 2 H(2)O. {ECO:0000269|PubMed:11032836, ECO:0000269|PubMed:12897770, ECO:0000269|PubMed:19812033}.
CofactorName=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:11032836}; Note=Binds 8 zinc ions per octamer. Requires four zinc ions per octamer for full catalytic activity. Can bind up to 2 zinc ions per subunit. {ECO:0000269|PubMed:11032836};
DiseaseAcute hepatic porphyria (AHEPP) [MIM:612740]: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AHP is characterized by attacks of gastrointestinal disturbances, abdominal colic, paralyses and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors. {ECO:0000269|PubMed:10706561, ECO:0000269|PubMed:1309003, ECO:0000269|PubMed:1569184, ECO:0000269|PubMed:2063868}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Enzyme RegulationCan alternate between a fully active homooctamer and a low-activity homohexamer. A bound magnesium ion may promote the assembly of the fully active homooctamer. The magnesium-binding site is absent in the low-activity homohexamer. Inhibited by compounds that favor the hexameric state. Inhibited by divalent lead ions. The lead ions partially displace the zinc cofactor. {ECO:0000269|PubMed:11032836, ECO:0000269|PubMed:12897770, ECO:0000269|PubMed:19812033}.
FunctionCatalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen. {ECO:0000269|PubMed:11032836, ECO:0000269|PubMed:19812033}.
PathwayPorphyrin-containing compound metabolism; protoporphyrin- IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.
PolymorphismThere are two common alleles of ALAD. Individuals heterozygous or homozygous for ALAD*2 Asn-59 have significantly higher blood lead levels than do ALAD*1 Lys-59 homozygotes when exposed to environmental lead.
Sequence CautionSequence=AAH00977.3; Type=Erroneous initiation; Evidence={ECO:0000305};
SimilarityBelongs to the ALAD family. {ECO:0000305}.
SubunitHomooctamer; active form. Homohexamer; low activity form. {ECO:0000269|PubMed:12897770, ECO:0000269|PubMed:19812033, ECO:0000269|Ref.13}.
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/alad/";
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