Information on EC 2.3.1.37 - 5-aminolevulinate synthase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY
2.3.1.37
-
RECOMMENDED NAME
GeneOntology No.
5-aminolevulinate synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
mechanism
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
mechanism
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
mechanism
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
mechanism
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
mechanism
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
mechanism
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
mechanism
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
mechanism
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
mechanism
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
mechanism
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
mechanism
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
covalent binding of pyridoxal 5'-phosphate and glycine to active site Lys131 is required for optimal activity
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
Tyr121, Asp279, Arg439, and Lys313 are involved in substrate and cofactor binding, mechanism, subunit localisation
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
cysteine in heme-regulatory motif
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
Lys313 acts as a general base during formation of the quinonoid reaction intermediates
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
the active site is located at the subunit interface and contains catalytically essential residues from the two subunits
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
three-step kinetic process, ordered kinetic mechanism, reaction mechanism
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
pyridoxal 5'-phosphate binding site, sequence and function of glycine-rich motif
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
ordered bi-bi mechanism in which glycine binds first and 5-aminolevulinic acid dissociates last
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
mechanism, aldimine linkage between pyridoxal 5-phosphate and enzyme
Q6RVB3
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
5-aminolevulinate synthase operates under the stereoelectronic control predicted by Dunathans hypothesis
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
mechanism, ordered bi-bi mechanism in which glycine binds first and 5-aminolevulinic acid dissociates last
Rhodobacter sphaeroides Y
-
-
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2
show the reaction diagram
mechanism, aldimine linkage between pyridoxal 5-phosphate and enzyme
Rhodopseudomonas palustris KUGB306
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
2-amino-3-hydroxycyclopent-2-enone biosynthesis
-
-
Glycine, serine and threonine metabolism
-
-
heme metabolism
-
-
Metabolic pathways
-
-
Porphyrin and chlorophyll metabolism
-
-
tetrapyrrole biosynthesis II (from glycine)
-
-
SYSTEMATIC NAME
IUBMB Comments
succinyl-CoA:glycine C-succinyltransferase (decarboxylating)
A pyridoxal-phosphate protein. The enzyme in erythrocytes is genetically distinct from that in other tissues.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5-aminolevulinate synthase
-
-
5-aminolevulinate synthase
-
-
5-aminolevulinate synthase
-
-
5-aminolevulinate synthetase
-
-
-
-
5-aminolevulinic acid synthetase
-
-
-
-
ALA synthase
-
-
-
-
ALA synthase
-
-
ALA synthase
Rattus norvegicus Sprague-Dawley
-
-
-
ALA synthetase
-
-
-
-
ALA-S
-
-
ALA-S
-
-
ALAS
-
-
-
-
ALAS
-
-
ALAS
Rattus norvegicus Sprague-Dawley
-
-
-
ALAS2
P22557
-
alpha-aminolevulinic acid synthase
-
-
-
-
aminolevulinate synthase
-
-
-
-
aminolevulinate synthetase
-
-
-
-
aminolevulinic acid synthase
-
-
-
-
aminolevulinic acid synthetase
-
-
-
-
aminolevulinic synthetase
-
-
-
-
delta-ALAS
-
-
delta-aminolevulinate synthase
-
-
-
-
delta-aminolevulinate synthase
-
-
delta-aminolevulinate synthase
Rattus norvegicus Sprague-Dawley
-
-
-
delta-aminolevulinate synthetase
-
-
-
-
delta-aminolevulinic acid synthase
-
-
-
-
delta-aminolevulinic acid synthetase
-
-
-
-
delta-aminolevulinic synthetase
-
-
-
-
mALAS-2
-
mature form of the murine erythroid specific isoform of aminolevulinate synthase
sigma-aminolevulinate synthase
-
-
sigma-aminolevulinate synthase
-
-
sigma-aminolevulinate synthase
-
-
synthase, aminolevulinate
-
-
-
-
synthetase, aminolevulinate
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9037-14-3
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
2 isoforms ALAS-1 and ALAS-2, a houskeeping form and an erythroid-specific form
-
-
Manually annotated by BRENDA team
animals after acetylphenylhydrazine-induced anemia
-
-
Manually annotated by BRENDA team
2 isoforms ALAS-1 and ALAS-2, a houskeeping form and an erythroid-specific form
-
-
Manually annotated by BRENDA team
isoform ALAS1
Uniprot
Manually annotated by BRENDA team
major splice variant of enzyme isoform ALAS2, expression in Escherichia coli
-
-
Manually annotated by BRENDA team
2 isoforms ALAS-1 and ALAS-2, a houskeeping form and an erythroid-specific form
-
-
Manually annotated by BRENDA team
Albino male CF1
-
-
Manually annotated by BRENDA team
erythroid specific isoform
-
-
Manually annotated by BRENDA team
erythroid-specific isoform
-
-
Manually annotated by BRENDA team
erythroid-specific isoform; gene ALAS-2
-
-
Manually annotated by BRENDA team
erythroid-specific isoform; gene ALAS-2; hypoxia-inducible
-
-
Manually annotated by BRENDA team
erythroid-specific isoform; gene ALAS-E
-
-
Manually annotated by BRENDA team
gene hemA
-
-
Manually annotated by BRENDA team
inducible in erythroleukemia cells
-
-
Manually annotated by BRENDA team
no activity in Chromatium sp.
-
-
-
Manually annotated by BRENDA team
2 enzyme forms in cytosol and mitochondria
-
-
Manually annotated by BRENDA team
i.e. Paracoccus denitrificans
-
-
Manually annotated by BRENDA team
in cells grown anaerobically and in iron-containing nitrate medium, overview
-
-
Manually annotated by BRENDA team
2 isoenzymes: I, constitutive, and II, inducible related to bacteriochlorophyll formation and light conditions
-
-
Manually annotated by BRENDA team
2 isoforms in cytosol and mitochondria
-
-
Manually annotated by BRENDA team
drug-induced
-
-
Manually annotated by BRENDA team
non-specific, housekeeping isoform ALAS-N and erythroid-specific isoform ALAS-E
-
-
Manually annotated by BRENDA team
Sprague-Dawley
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprague-Dawley
Sprague-Dawley
-
-
Manually annotated by BRENDA team
2 isozymes; Y
-
-
Manually annotated by BRENDA team
enzyme exists in an inactive or low activity form which can under certain conditions become activated, spontaneous activation in presence of oxygen or an oxidizing agent shows a pH dependence with an optimum at about pH 7.0, assisted by 2-mercaptoethanol
-
-
Manually annotated by BRENDA team
expression in Escherichia coli
-
-
Manually annotated by BRENDA team
Rhodobacter sphaeroides Y
Y
-
-
Manually annotated by BRENDA team
strain KUGB306
Swissprot
Manually annotated by BRENDA team
Rhodopseudomonas palustris KUGB306
strain KUGB306
Swissprot
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
mutation in Alas gena cause massive water loss. The cuticle of alas mutant larvae detaches from the epidermis and its basal region is frayed. Reduction of Alas function results in weakening of the extracellular dityrosines network in the cuticle. Alas activity, which initiates heme biosynthesis in the mitochondrion, might be needed for the formation of a dityrosine-based barrier that confers resistance to the internal hydrostatic pressure protecting both the cuticle from transcellular infiltration of body fluid and the animal from dehydration
physiological function
-
construction of a green fluorescent protein knock-in mouse line in which the Alas1 gene encoding ALAS-N is replaced with a green fluorescent protein gene. Mice bearing a homozygous knock-in allele Alas1GFP /GFP are lethal by embryonic day 8.5. The Alas1 expression level differs substantially in tissues
physiological function
-
silencing by shRNA results in a decrease in iron-induced expression of band 3 protein
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-hydroxybutanoyl-CoA + glycine
? + CoA + CO2
show the reaction diagram
-
-
-
-
?
acetyl-CoA + glycine
?
show the reaction diagram
-
low activity
-
-
?
butanoyl-CoA + glycine
? + CoA + CO2
show the reaction diagram
-
-
-
-
?
butyryl-CoA + glycine
?
show the reaction diagram
-
low activity
-
-
?
octanoyl-CoA + glycine
? + CoA + CO2
show the reaction diagram
-
-
-
-
?
propionyl-CoA + glycine
?
show the reaction diagram
-
low activity
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
ir
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
Q6RVB3
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
common intermediate in the biosynthesis of chlorophyll and heme
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
absolute requirement for glycine
-
ir
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
absolute requirement for glycine
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
absolute requirement for glycine
-
ir
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
absolute requirement for glycine
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
absolute requirement for glycine
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
absolute requirement for glycine
-
ir
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
absolute requirement for glycine
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
absolute requirement for glycine
-
ir
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
absolute requirement for succinyl-CoA
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
absolute requirement for succinyl-CoA
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
absolute requirement for succinyl-CoA
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
enzyme utilizes acetyl-CoA, propionyl-CoA and butyryl-CoA at much lower rates
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
glycine is formed by the reverse reaction under optimum conditions at 4-5% the rate of 5-aminolevulinate formed by the forward reaction under optimum conditions
-
r
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
absolutely specific for glycine
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
cellular iron status plays a regulatory role
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
regulatory mechanisms in hepatic and erythroid cells
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
first step in heme biosynthesis pathway
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
first step in heme biosynthesis pathway
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
first step in heme biosynthesis pathway
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
ALAS2 synthesizes heme specifically for haemoglobin
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
first and rate-limiting step of heme biosynthesis. Repression of 5-aminolevulinate synthase gene by the potent tumor promoter, TPA, involves multiple signal transduction pathways
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
5-aminolevulinate synthase operates under the stereoelectronic control predicted by Dunathans hypothesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
Rhodobacter sphaeroides Y
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
Rhodobacter sphaeroides Y
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
Rhodobacter sphaeroides Y
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
Rhodopseudomonas palustris KUGB306
Q6RVB3
-
-
-
?
succinyl-CoA-monomethyl ester + glycine
5-aminolevulinic acid methyl ester + CoA + CO2
show the reaction diagram
-
at 80% the rate of the reaction with succinyl-CoA
-
-
-
glutaryl-CoA + glycine
? + CoA + CO2
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
enzyme deficiency causes X-linked sideroblastic anemia
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
-
common intermediate in the biosynthesis of chlorophyll and heme
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
key enzyme in tetrapyrrole biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
cellular iron status plays a regulatory role
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
regulatory mechanisms in hepatic and erythroid cells
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
first step in heme biosynthesis pathway
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
first step in heme biosynthesis pathway
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
first step in heme biosynthesis pathway
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
rate-limiting enzyme of heme biosynthesis
-
-
?
succinyl-CoA + glycine
5-aminolevulinate + CoA + CO2
show the reaction diagram
-
ALAS2 synthesizes heme specifically for haemoglobin
-
-
?
additional information
?
-
-
enzyme deficiency causes X-linked sideroblastic anemia
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N-methyl-pyridoxal 5'-phosphate
-
in vitro, mutant D279A
pyridoxal 5'-phosphate
-
activates; required
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
absolute requirement
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
fully active with 0.05 mM pyridoxal 5'-phosphate; weekly bound
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
bound to the enzyme through a Schiff base linkage
pyridoxal 5'-phosphate
-
1 or 2 molecules of cofactor are bound per subunit of MW 50000 in hemiapoenzyme or holoenzyme, required
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
required
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
contains 1 molar equivalent of pyridoxal 5'-phosphate
pyridoxal 5'-phosphate
-
content in ALAS-E wild-type and Lys313 mutants; required
pyridoxal 5'-phosphate
-
required
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
required
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
required
pyridoxal 5'-phosphate
-
required
pyridoxal 5'-phosphate
-
noncovalently bound; required
pyridoxal 5'-phosphate
-
required
pyridoxal 5'-phosphate
-
required
pyridoxal 5'-phosphate
-
required
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
dependent on
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
-
pyridoxal 5'-phosphate
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
optimal at concentration of 50 mM, inhibition above 200 mM
Iron
-
regulation of erythroid-specific isoform ALAS-2 via 5'-iron responsive element, i.e. IRE
Li+
-
in Mg2+-containing medium: at 100 mM no effect on activity, higher concentrations are totally inhibitory; optimal at 0.5 M, not inhibitory up to 1 M
Li+
-
in Mg2+-containing medium: at 100 mM no effect on activity, higher concentrations are totally inhibitory
Mg2+
-
activates
Mg2+
-
optimal at concentration of 50 mM, inhibition above 200 mM
Na+
-
in Mg2+-containing medium: at 100 mM no effect on activity, higher concentrations are totally inhibitory; optimal at 0.5 M, not inhibitory up to 1 M
Na+
-
in Mg2+-containing medium: at 100 mM no effect on activity, higher concentrations are totally inhibitory
Na+
-
inhibition of complex form, stimulation of stripped form
potassium ferricyanide
-
activates at 0.5 mM
Mg2+
-
inhibition of complex form, stimulation of stripped form
additional information
-
partially purified enzyme requires high cation concentrations, equivalent to 0.3 M NaCl, for maximum activation, monovalent cations, i.e. Na+, K+, Li+, Rb+ or NH4+, in concentrations from 0.15 M to 0.30 M or divalent cations, i.e. Mg2+, Ca2+ or Mn2+, at lower concentrations of 0.03 M to 0.10 M are effective
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-hydroxyethyldisulfide
-
-
2-mercaptoethanol
-
slightly at high concentration, 10 mM
2-mercaptoethanol
-
-
2-mercaptoethanol
-
-
Aminomalonate
-
-
Aminomalonate
-
competitive versus glycine
Aminomalonate
-
weak
Aminomethylphosphonate
-
-
bilirubin
-
-
Borohydride
-
in presence of pyridoxal 5'-phosphate
Borohydride
-
aminomalonate protects; in presence of pyridoxal 5'-phosphate
Chloramphenicol
-
-
chlorophyllide a
-
-
Co2+
-
accumulation of Co2+-protoporphyrin containing products of hemolysis
Co2+
Q6RVB3
1 mM, strong
CoA
-
noncompetitive
Cu2+
-
isoenzyme a
Cu2+
-
at low concentration
Cu2+
Q6RVB3
1 mM, complete inhibition
cyanide
-
-
delta-aminolevuinate
-
product inhibition
delta-aminolevuinate
-
competitive against glycine, noncompetitive against succinyl-CoA
deuteroporphyrin
-
-
Diethyl aminomalonate
-
-
dithiothreitol
-
-
Divalent cations
-
at high concentration, relative order of inhibition: Co2+, Mn2+, Mg2+, Ca2+
-
Divalent cations
-
Mg2+ or Ca2+: optimal at concentration of 50 mM, inhibition above 200 mM
-
ethanolamine
-
-
Fe2+
Q6RVB3
1 mM, strong
Fe3+
-
no inhibition
FeCl3
-
addition of imidazole at 0.2 mM prior to FeCl3 prevents inhibition
ferroheme
-
not heme
glutathione
-
-
Hemin
-
feed-back inhibition
Hemin
-
reversible, noncompetitive
Hemin
-
feed-back inhibition
Hemin
-
albumin protects; feed-back inhibition
Hemin
-
no inhibition
Hemin
-
no inhibition of rat fetal liver enzyme
Hemin
-
feed-back inhibition
Hemin
-
inhibition of the import of the enzyme into the mitochondrial matrix
Hemin
-
inhibition of the import of the enzyme into the mitochondrial matrix
Hemin
-
inhibition of the import of the enzyme into the mitochondrial matrix
Hemin
-
inhibition of the import of the enzyme into the mitochondrial matrix
Hg2+
-
isoenzyme a
Hg2+
-
2-mercaptoethanol protects partly
Iron-deuteroporphyrin
-
-
Iron-mesoporphyrin
-
-
Iron-protoporphyrin
-
-
K+
Q6RVB3
slight inhibition
L-cysteine
-
-
L-Penicillamine
-
-
light
-
above 30 lux intensity
-
mesoporphyrin
-
-
Metalloporphyrins
-
-
-
Mg-protoporphyrin
-
-
Mg2+
-
inhibition of complex form, stimulation of stripped form
Mg2+
Q6RVB3
slight inhibition
Monovalent cations
-
Na+ or Li+: optimal at 0.5 M, not inhibitory up to 1 M
-
N-ethylmaleimide
-
glycine and pyridoxal 5'-phosphate protect
N-ethylmaleimide
-
-
N-ethylmaleimide
-
2-mercaptoethanol protect
Na+
-
inhibition of complex form, stimulation of stripped form
NaCl
-
fetal rat liver enzyme
p-chloromercuribenzoate
-
pyridoxal 5'-phosphate protects
p-chloromercuribenzoate
-
isoenzyme a
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
2-mercaptoethanol protect partly
Pb2+
Q6RVB3
1 mM, strong
Propanolol
-
-
protoheme
-
feed-back inhibition, non-specific isoform ALAS-1
protoporphyrin
-
-
protoporphyrin
-
-
protoporphyrin
-
weak
succinyl-CoA
-
non-specific isoform ALAS-N in absence of ATP
tergitol
-
fetal enzyme
Zn2+
Q6RVB3
1 mM, complete inhibition
Monovalent cations
-
in Mg2+-containing medium: Na+ or Li+ at 100 mM have no effect on activity, higher concentrations are totally inhibitory
-
additional information
-
pheophytin and chlorophyll are not inhibitory
-
additional information
-
cysteine, glutathione, cystine or 2-mercaptoethanol diminishes activity in presence of 5-aminolevulinate
-
additional information
-
product inhibition pattern for the forward reaction and the reverse reaction
-
additional information
-
presence of high salt concentration in the sample buffer and running buffer of aggregated enzyme preparation results in inactivation
-
additional information
-
not inhibitory: D-glucose, D-fructose, D-xylose, D-mannose, L-arabinose, D-galactose, lactose, sucrose and maltose
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-allyl-2-isopropylacetamide
-
strong induction of enzyme in liver
2-allyl-2-isopropylacetamide
-
strong induction of enzyme in liver
3,5-di-carbethoxy-1,4-dihydrocillidine
-
strong induction of enzyme in liver
-
Activator protein
-
from rat liver mitochondria possibly activates by formation of high molecular weight aggregates of delta-aminolevulinic acid synthetase
-
Activator protein
-
from Rhodopseudomonas sphaeroides
-
ATP
-
activates in assays with crude enzyme extracts
ATP
-
slight activation, erythroid-specific isoform
Butyric acid
-
induction of enzyme expression, erythroleukemia cells
CoA
-
activates
Dimethylsulfoxide
-
induction of enzyme expression, erythroleukemia cells
dithiothreitol
-
activates
hexamethylene diacetamide
-
induction of enzyme expression, erythroleukemia cells
NaCl
-
required for maximal activity
native activator protein
-
purified from hepatic extract
-
native activator protein
-
purified from cell extract
-
O2
-
1%, 3fold increase in expression level, promotor activation in transiently transfected HeLa cells, hypoxia-inducible erythroid-isoform
phosphate
-
enzyme is maximally active in presence of 0.005 mM phosphate
Lubrol
-
activates, fetal enzyme
-
additional information
-
1-2 low molecular-weight compounds which stimulate or stabilize activity found by dialysis of crude extract
-
additional information
-
iron depletion does not increase isoform II promotor activity
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0055
2-Hydroxybutanoyl-CoA
-
mutant R85K, pH 7.5, 30C
0.0061
2-Hydroxybutanoyl-CoA
-
mutant R85L, pH 7.5, 30C
0.0098
2-Hydroxybutanoyl-CoA
-
wild-type, pH 7.5, 30C
0.0742
2-Hydroxybutanoyl-CoA
-
mutant R85L/T430V, pH 7.5, 30C
0.00054
Butanoyl-CoA
-
mutant R85L/T430V, pH 7.5, 30C
0.0027
Butanoyl-CoA
-
mutant R85K, pH 7.5, 30C
0.0061
Butanoyl-CoA
-
wild-type, pH 7.5, 30C
0.0093
Butanoyl-CoA
-
mutant R85L, pH 7.5, 30C
0.0075
glutaryl-CoA
-
mutant R85K, pH 7.5, 30C
0.017
glutaryl-CoA
-
wild-type, pH 7.5, 30C
0.0301
glutaryl-CoA
-
mutant R85L, pH 7.5, 30C
0.00032
glycine
-
pH 7.5, 30C, ALAS(K313A mutant)/ALAS
0.00045
glycine
-
pH 7.5, 30C, ALAS/ALAS
0.001
glycine
-
mutant Y428I/R433Q /G434N/E435T/L437N, pH 7.5, 20C
0.0015
glycine
-
mutant N427H, pH 7.5, 20C
0.0017
glycine
-
mutant L437Q, pH 7.5, 20C
0.0018
glycine
-
pH 7.5, 30C, ALAS/ALAS (K313A mutant)
0.002
glycine
-
pH 7.5, 30C, ALAS
0.002
glycine
-
mutant Y428N/P432N/R433I/G434E/E435K/L437K, pH 7.5, 20C
0.0023
glycine
-
mutant A425T, pH 7.5, 20C; mutant V423I/A425P/Y428C/P432R/R433K/E435N, pH 7.5, 20C
0.0026
glycine
-
mutant A425G/Y428H/R433H/G434N/E435K/L437K, pH 7.5, 20C
0.0029
glycine
-
mutant R433K/G434K/E435Q/L437Q, pH 7.5, 20C
0.003
glycine
-
mutant V423L/Y428R/P432E/R433I/G434N/E435Q/L437K, pH 7.5, 20C
0.011
glycine
-
wild-type, pH 7.5, 20C
0.0171
glycine
-
wild-type, cosubstrate octanoyl-CoA, pH 7.5, 30C
0.0172
glycine
-
mutant R85K, cosubstrate butanoyl-CoA, pH 7.5, 30C
0.0182
glycine
-
mutant R85K, cosubstrate 2-hydroxybutanoyl-CoA, pH 7.5, 30C
0.02
glycine
-
mutant R85K, cosubstrate succinyl-CoA, pH 7.5, 30C
0.0212
glycine
-
mutant R85K, cosubstrate glutaryl-CoA, pH 7.5, 30C
0.0221
glycine
-
wild-type, cosubstrate 2-hydroxybutanoyl-CoA, pH 7.5, 30C
0.0242
glycine
-
wild-type, cosubstrate succinyl-CoA, pH 7.5, 30C
0.0252
glycine
-
mutant R85K, cosubstrate octanoyl-CoA, pH 7.5, 30C
0.0284
glycine
-
wild-type, cosubstrate glutaryl-CoA, pH 7.5, 30C
0.0293
glycine
-
wild-type, cosubstrate butanoyl-CoA, pH 7.5, 30C
0.0552
glycine
-
mutant R85L, cosubstrate octanoyl-CoA, pH 7.5, 30C
0.0591
glycine
-
mutant R85L, cosubstrate 2-hydroxybutanoyl-CoA, pH 7.5, 30C
0.0631
glycine
-
mutant R85L, cosubstrate succinyl-CoA, pH 7.5, 30C
0.0703
glycine
-
mutant R85L, cosubstrate butanoyl-CoA, pH 7.5, 30C
0.0706
glycine
-
mutant R85L, cosubstrate glutaryl-CoA, pH 7.5, 30C
0.0742
glycine
-
mutant cosubstrate octanoyl-CoA, R85L/T430V, pH 7.5, 30C
0.0882
glycine
-
mutant cosubstrate butanoyl-CoA, R85L/T430V, pH 7.5, 30C
0.0922
glycine
-
mutant cosubstrate 2-hydroxybutanoyl-CoA, R85L/T430V, pH 7.5, 30C
0.0984
glycine
-
mutant cosubstrate succinyl-CoA, R85L/T430V, pH 7.5, 30C
1.05
glycine
-
-
2 - 3
glycine
-
pH 7.5, 30C, wild-type
2 - 3
glycine
-
pH 7.5, 30C, ALAS
2.01
glycine
Q6RVB3
pH 7.5
2.5
glycine
-
papain untreated enzyme
4
glycine
-
-
6.2
glycine
-
recombinant mutant G144T
6.5
glycine
-
erythroid-specific isoform
6.95
glycine
-
recombinant mutant dimer K149A/K313A
7.5
glycine
-
papain treated enzyme
8.33
glycine
-
-
8.39
glycine
-
-
9.3
glycine
-
recombinant mutant G144A
11.7
glycine
-
recombinant erythroid isoform
11.7
glycine
-
pH 7.5, 20C, mutant 2XALAS
11.8
glycine
-
pH 7.5, 30C, ALAS/ALAS (K313A mutant)
11.9
glycine
-
recombinant mutant G144S
12
glycine
-
-
12
glycine
-
mutant V423L/Y428R/P432E/R433I/G434N/E435Q/L437K, pH 7.5, 20C
12.5
glycine
-
recombinant erythroid isoform
13
glycine
-
mutant A425G/Y428H/R433H/G434N/E435K/L437K, pH 7.5, 20C; mutant Y428N/P432N/R433I/G434E/E435K/L437K, pH 7.5, 20C
14
glycine
-
pH 7.5, 20C, wild-type
14
glycine
-
mutant V423I/A425P/Y428C/P432R/R433K/E435N, pH 7.5, 20C; wild-type, pH 7.5, 20C
14.4
glycine
-
recombinant erythroid isoform mutant R433K
14.8
glycine
-
pH 7.5, 30C, ALAS(K313A mutant)/ALAS
15
glycine
-
mutant N427H, pH 7.5, 20C
16
glycine
-
mutant R433K/G434K/E435Q/L437Q, pH 7.5, 20C; mutant Y428I/R433Q /G434N/E435T/L437N, pH 7.5, 20C
16.7
glycine
-
pH 7.5, 30C, mutant 2XALAS
16.7
glycine
-
pH 7.5, 30C, ALAS/ALAS
18
glycine
-
mutant S254A, 30C, pH 7.5
18.4
glycine
-
recombinant erythroid isoform mutant R433L
19
glycine
-
-
23
glycine
-
recombinant erythroid isoform wild-type
24
glycine
-
mutant L437Q, pH 7.5, 20C
25
glycine
-
wild-type, 30C, pH 7.5
25
glycine
-
mutant A425T, pH 7.5, 20C
27
glycine
-
mutant S254T, 30C, pH 7.5
50
glycine
-
recombinant enzyme
51
glycine
-
recombinant protein
51
glycine
-
-
52.2
glycine
-
recombinant mutant G142C
52.2
glycine
-
recombinant mutant Y121H
103
glycine
-
recombinant erythroid isoform mutant R439K
140
glycine
-
recombinant erythroid isoform mutant D279E
0.0018
Octanoyl-CoA
-
mutant R85L, pH 7.5, 30C
0.0034
Octanoyl-CoA
-
wild-type, pH 7.5, 30C
0.0103
Octanoyl-CoA
-
mutant R85K, pH 7.5, 30C
0.0172
Octanoyl-CoA
-
mutant R85L/T430V, pH 7.5, 30C
0.00077
pyridoxal 5'-phosphate
-
-
0.001 - 0.01
pyridoxal 5'-phosphate
-
-
0.015
pyridoxal 5'-phosphate
-
-
0.003
pyridoxal phosphate
-
-
0.00064
succinyl-CoA
-
recombinant mutant G144A
0.0012
succinyl-CoA
-
recombinant erythroid isoform and mutant G144S
0.0012
succinyl-CoA
-
mutant S254T, 30C, pH 7.5
0.0013
succinyl-CoA
-
wild-type, 30C, pH 7.5
0.0016
succinyl-CoA
-
recombinant mutant Y121H
0.0019
succinyl-CoA
-
recombinant mutant G144T
0.002
succinyl-CoA
-
-
0.002
succinyl-CoA
-
erythroid-specific isoform
0.002
succinyl-CoA
-
recombinant mutant G142C
0.002
succinyl-CoA
-
recombinant erythroid isoform wild-type
0.0022
succinyl-CoA
-
recombinant erythroid isoform mutant R433K
0.0029
succinyl-CoA
-
wild-type, pH 7.5, 30C
0.0032
succinyl-CoA
-
recombinant erythroid isoform mutant R433L
0.01
succinyl-CoA
-
-
0.011
succinyl-CoA
-
-
0.0124
succinyl-CoA
-
mutant R85K, pH 7.5, 30C
0.013
succinyl-CoA
-
-
0.014
succinyl-CoA
-
recombinant mutant Y121F
0.02
succinyl-CoA
-
-
0.0203
succinyl-CoA
-
mutant R85L, pH 7.5, 30C
0.025
succinyl-CoA
-
-
0.027
succinyl-CoA
-
recombinant erythroid isoform mutant R439K
0.032
succinyl-CoA
-
mutant S254A, 30C, pH 7.5
0.035
succinyl-CoA
-
recombinant erythroid isoform mutant D279E
0.055
succinyl-CoA
-
recombinant protein
0.055
succinyl-CoA
-
-
0.07
succinyl-CoA
-
-
0.096
succinyl-CoA
-
mutant R85L/T430V, pH 7.5, 30C
0.1
succinyl-CoA
-
recombinant enzyme
0.2
succinyl-CoA
-
-
0.45
succinyl-CoA
-
pH 7.5, 30C, mutant 2XALAS
0.63
succinyl-CoA
-
pH 7.5, 20C, mutant 2XALAS
1.52
succinyl-CoA
-
recombinant mutant dimer K149A/K313A
1.82
succinyl-CoA
-
-
2.3
succinyl-CoA
-
pH 7.5, 30C, wild-type
5
succinyl-CoA
-
-
10
succinyl-CoA
-
-
10
succinyl-CoA
-
-
11
succinyl-CoA
-
pH 7.5, 20C, wild-type
49.55
succinyl-CoA
Q6RVB3
pH 7.5
400
glycine
-
recombinant mutant Y121F
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
overview
-
additional information
additional information
-
-
-
additional information
additional information
-
overview
-
additional information
additional information
-
-
-
additional information
additional information
-
overview
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.01
2-Hydroxybutanoyl-CoA
-
mutant R85L, pH 7.5, 30C
0.047
2-Hydroxybutanoyl-CoA
-
mutant R85K, pH 7.5, 30C
0.067
2-Hydroxybutanoyl-CoA
-
wild-type, pH 7.5, 30C
0.001
Butanoyl-CoA
-
mutant R85L/T430V, pH 7.5, 30C
0.0335
Butanoyl-CoA
-
mutant R85L, pH 7.5, 30C
0.105
Butanoyl-CoA
-
wild-type, pH 7.5, 30C
0.17
Butanoyl-CoA
-
mutant R85K, pH 7.5, 30C
0.037
glutaryl-CoA
-
mutant R85L, pH 7.5, 30C
0.05
glutaryl-CoA
-
mutant R85K, pH 7.5, 30C
0.117
glutaryl-CoA
-
wild-type, pH 7.5, 30C
0.016
glycine
-
pH 7.5, 20C, wild-type
0.02
glycine
-
wild-type, co-substrate: succinyl-CoA, pH 7.5, 20C
0.03
glycine
-
co-substrate: succinyl-CoA, mutant L437Q, pH 7.5, 20C
0.05
glycine
-
mutant S254T, 30C, pH 7.5
0.07
glycine
-
pH 7.5, 30C, ALAS/ALAS (K313A mutant)
0.07
glycine
-
co-substrate: succinyl-CoA, mutant A425T, pH 7.5, 20C; co-substrate: succinyl-CoA, mutant N427H, pH 7.5, 20C
0.11
glycine
-
pH 7.5, 20C, mutant 2XALAS
0.14
glycine
-
wild-type, 30C, pH 7.5
0.16
glycine
-
co-substrate: succinyl-CoA, mutant V423I/A425P/Y428C/P432R/R433K/E435N, pH 7.5, 20C
0.166
glycine
-
pH 7.5, 30C, ALAS
0.167
glycine
-
pH 7.5, 30C, wild-type
0.17
glycine
-
co-substrate: succinyl-CoA, mutant Y428I/R433Q /G434N/E435T/L437N, pH 7.5, 20C
0.2
glycine
-
co-substrate: succinyl-CoA, mutant A425G/Y428H/R433H/G434N/E435K/L437K, pH 7.5, 20C; co-substrate: succinyl-CoA, mutant R433K/G434K/E435Q/L437Q, pH 7.5, 20C
0.23
glycine
-
co-substrate: succinyl-CoA, mutant Y428N/P432N/R433I/G434E/E435K/L437K, pH 7.5, 20C
0.27
glycine
-
mutant S254A, 30C, pH 7.5
0.31
glycine
-
co-substrate: succinyl-CoA, mutant V423L/Y428R/P432E/R433I/G434N/E435Q/L437K, pH 7.5, 20C
0.36
glycine
-
pH 7.5, 30C, ALAS(K313A mutant)/ALAS
0.92
glycine
-
pH 7.5, 30C, mutant 2XALAS
0.92
glycine
-
pH 7.5, 30C, ALAS/ALAS
0.00002
Octanoyl-CoA
-
mutant R85L/T430V, pH 7.5, 30C
0.03
Octanoyl-CoA
-
mutant R85L, pH 7.5, 30C
0.172
Octanoyl-CoA
-
mutant R85K, pH 7.5, 30C
0.34
Octanoyl-CoA
-
wild-type, pH 7.5, 30C
0.002
succinyl-CoA
-
mutant R85L/T430V, pH 7.5, 30C
0.0095
succinyl-CoA
-
-
0.016
succinyl-CoA
-
mutant R85L, pH 7.5, 30C
0.0183
succinyl-CoA
-
recombinant erythroid isoform mutant G142C
0.0355
succinyl-CoA
-
recombinant erythroid isoform mutant Y121H
0.0633
succinyl-CoA
-
recombinant erythroid isoform mutant G144T
0.0967
succinyl-CoA
-
recombinant erythroid isoform mutant D279E
0.107
succinyl-CoA
-
mutant R85K, pH 7.5, 30C
0.12
succinyl-CoA
-
recombinant erythroid isoform mutant G144S
0.132
succinyl-CoA
-
recombinant erythroid isoform mutant G144A
0.167
succinyl-CoA
-
recombinant erythroid isoform
0.167
succinyl-CoA
-
wild-type, pH 7.5, 30C
0.235
succinyl-CoA
-
recombinant erythroid isoform mutant Y121F
0.308
succinyl-CoA
-
recombinant erythroid isoform
0.508
succinyl-CoA
-
recombinant erythroid mutant R439K
0.658
succinyl-CoA
-
recombinant erythroid isoform
0.842
succinyl-CoA
-
recombinant erythroid mutant R433L
1.35
succinyl-CoA
-
recombinant erythroid mutant R433K
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0018
2-Hydroxybutanoyl-CoA
-
mutant R85L, pH 7.5, 30C
7991
0.007
2-Hydroxybutanoyl-CoA
-
wild-type, pH 7.5, 30C
7991
0.0085
2-Hydroxybutanoyl-CoA
-
mutant R85K, pH 7.5, 30C
7991
0.022
2-Hydroxybutanoyl-CoA
-
mutant R85L/T430V, pH 7.5, 30C
7991
0.0005
Butanoyl-CoA
-
mutant R85L/T430V, pH 7.5, 30C
802
0.0035
Butanoyl-CoA
-
mutant R85L, pH 7.5, 30C
802
0.02
Butanoyl-CoA
-
wild-type, pH 7.5, 30C
802
0.062
Butanoyl-CoA
-
mutant R85K, pH 7.5, 30C
802
0.0007
glutaryl-CoA
-
mutant R85K, pH 7.5, 30C
656
0.0012
glutaryl-CoA
-
mutant R85L, pH 7.5, 30C
656
0.0068
glutaryl-CoA
-
wild-type, pH 7.5, 30C
656
0.00002
glycine
-
mutant cosubstrate succinyl-CoA, R85L/T430V, pH 7.5, 30C
72
0.00017
glycine
-
mutant R85K, cosubstrate glutaryl-CoA, pH 7.5, 30C
72
0.00018
glycine
-
mutant R85L, cosubstrate 2-hydroxybutanoyl-CoA, pH 7.5, 30C
72
0.0002
glycine
-
mutant R85L, cosubstrate succinyl-CoA, pH 7.5, 30C
72
0.0005
glycine
-
mutant R85L, cosubstrate butanoyl-CoA, pH 7.5, 30C; mutant R85L, cosubstrate octanoyl-CoA, pH 7.5, 30C
72
0.0019
glycine
-
mutant S254T, 30C, pH 7.5
72
0.0023
glycine
-
mutant R85K, cosubstrate 2-hydroxybutanoyl-CoA, pH 7.5, 30C
72
0.0028
glycine
-
wild-type, cosubstrate 2-hydroxybutanoyl-CoA, pH 7.5, 30C
72
0.0043
glycine
-
wild-type, cosubstrate butanoyl-CoA, pH 7.5, 30C
72
0.0048
glycine
-
wild-type, cosubstrate glutaryl-CoA, pH 7.5, 30C
72
0.005
glycine
-
mutant R85K, cosubstrate succinyl-CoA, pH 7.5, 30C
72
0.0056
glycine
-
wild-type, 30C, pH 7.5
72
0.0067
glycine
-
wild-type, cosubstrate succinyl-CoA, pH 7.5, 30C
72
0.0083
glycine
-
mutant R85K, cosubstrate butanoyl-CoA, pH 7.5, 30C
72
0.0087
glycine
-
mutant R85K, cosubstrate octanoyl-CoA, pH 7.5, 30C
72
0.015
glycine
-
mutant S254A, 30C, pH 7.5
72
0.02
glycine
-
mutant cosubstrate octanoyl-CoA, R85L/T430V, pH 7.5, 30C; wild-type, cosubstrate octanoyl-CoA, pH 7.5, 30C
72
0.13
glycine
-
mutant R85L, cosubstrate glutaryl-CoA, pH 7.5, 30C
72
0.055
Octanoyl-CoA
-
mutant R85L, pH 7.5, 30C
385
0.113
Octanoyl-CoA
-
wild-type, pH 7.5, 30C
385
0.117
Octanoyl-CoA
-
mutant R85K, pH 7.5, 30C
385
0.0002
succinyl-CoA
-
mutant R85L/T430V, pH 7.5, 30C
224
0.0008
succinyl-CoA
-
mutant R85L, pH 7.5, 30C
224
0.0084
succinyl-CoA
-
mutant S254A, 30C, pH 7.5
224
0.0089
succinyl-CoA
-
mutant R85K, pH 7.5, 30C
224
0.042
succinyl-CoA
-
mutant S254T, 30C, pH 7.5
224
0.11
succinyl-CoA
-
wild-type, 30C, pH 7.5
224
0.55
succinyl-CoA
-
wild-type, pH 7.5, 30C
224
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.23
5-aminolevulinate
-
versus glycine
0.023
Aminomalonate
-
-
10
Aminomethylphosphonate
-
-
0.12
CoA
-
versus glycine
0.035
Hemin
-
-
0.2
metalloporphyrin
-
-
-
additional information
additional information
-
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0037
-
crude enzyme extract
0.0057
-
maximal enzyme activity after 3 weeks of storage of tubers at 0-15C at 30 lux
0.018
-
purified enzyme
0.035
-
purified enzyme
0.091
-
purified enzyme
0.16
-
purified enzyme
0.167
-
isozyme II
0.35
-
purified enzyme
0.375
-
purified isozyme I
0.558
-
purified enzyme
0.58
-
purified enzyme
0.62
-
purified enzyme
0.65
-
purified enzyme
1.22
-
purified enzyme
1.34
-
purified enzyme
1.87
-
purified erythroid-specific isoform
2.17 - 2.83
-
purified enzyme
2.17
-
purified enzyme
2.22
-
purified enzyme
27.73
Q6RVB3
pH 7.5
additional information
-
EDTA required for the assay to inhibit 5-aminolevulinate dehydratase
additional information
-
-
additional information
-
-
additional information
-
active and inactive forms, inactive form can be activated by addition of rat mitochondrial protein extract
additional information
-
activation of inactive enzyme form required activator protein and L-cystine
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
enzyme expressed in transgenic tabacco plants
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 8
-
-
7
-
0.1 M phosphate buffer
7.1 - 7.5
-
isoenzyme A
7.4 - 7.6
-
-
7.5
-
0.1 M Tris-HCl buffer
7.5
-
assay at
7.5
-
assay at
7.6
-
erythroid-specific isoform
8.5
-
erythroid-specific isoform
additional information
-
pI: 7.5
additional information
-
pI: 5.5
additional information
-
pI
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.8 - 8.6
-
about 50% of activity maximum at pH 5.8 and pH 8.6
6.5 - 9.5
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20
-
assay at
30
-
assay at
30
-
assay at
30
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
sodium butyrate treatment activates ALAS2 gene transcription
Manually annotated by BRENDA team
-
high expression of isoform ALAS1
Manually annotated by BRENDA team
-
ALA-S activity is induced by acute administration of anaesthetics (89%), veronal (240%), and ethanol (80). ALA-S mRNA expression augmented by chronic administration of eflurane, allylisopropylacetamide and veronal
Manually annotated by BRENDA team
-
high activity in cells grown anaerobically in defined medium, low in cells grown in an iron-deficient medium and in cells grown aerobically
Manually annotated by BRENDA team
-
high expression of isoform ALAS1
Manually annotated by BRENDA team
-
high expression of isoform ALAS1
Manually annotated by BRENDA team
-
enzyme in erythrocytes is genetically distinct from that in other tissue
Manually annotated by BRENDA team
-
erythroid induction cultures of CD34+ hematopoietic stem/progenitor cells
Manually annotated by BRENDA team
-
erythroid-specific isoform
Manually annotated by BRENDA team
-
including submandibular and parotid glands, high expression of ALAS1
Manually annotated by BRENDA team
-
sodium butyrate treatment activates ALAS2 gene transcription
Manually annotated by BRENDA team
-
high expression of isoform ALAS1
Manually annotated by BRENDA team
-
ALAS2 is expressed exclusively in erythroid cells
Manually annotated by BRENDA team
-
sodium butyrate treatment activates ALAS2 gene transcription
Manually annotated by BRENDA team
-
high expression of isoform ALAS1
Manually annotated by BRENDA team
-
rapid stimulation of ALA-s mRNA by ACTH which acts through cyclic AMP
Manually annotated by BRENDA team
-
high expression of isoform ALAS1
Manually annotated by BRENDA team
-
high expression of isoform ALAS1
Manually annotated by BRENDA team
-
high expression of isoform ALAS1
Manually annotated by BRENDA team
-
dim light and cold-stored, green skin peeling
Manually annotated by BRENDA team
-
increased activity of ALA synthase which is the rate-limiting enzyme of heme biosynthesis, in the liver of the fatigued animals
Manually annotated by BRENDA team
additional information
-
import into mitochondria
Manually annotated by BRENDA team
additional information
-
enzyme is synthezised in the cytosol as the precursor protein and then imported into the mitochondria matrix and cleaved to the mature enzyme, the targeting information is encoded in nonoverlapping regions of the presequence
Manually annotated by BRENDA team
additional information
-
enzyme is synthezised in the cytosol as the precursor protein and then imported into the mitochondria matrix and cleaved to the mature enzyme, the targeting information is encoded in nonoverlapping regions of the presequence
Manually annotated by BRENDA team
additional information
-
infusion of rats with ACTH for 1 h caused an increase of adrenal ALA-s mRNA and activity
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Rhodobacter capsulatus (strain ATCC BAA-309 / NBRC 16581 / SB1003)
Rhodobacter capsulatus (strain ATCC BAA-309 / NBRC 16581 / SB1003)
Rhodobacter capsulatus (strain ATCC BAA-309 / NBRC 16581 / SB1003)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
57000
-
gel filtration
486811
58000
-
monomer, gel filtration
486822
61000 - 64000
-
isoenzyme II, gel filtration
486840
61000 - 65000
-
-
486815
61000
-
gel filtration
486842
62000 - 68000
-
gel filtration
486825
64840
-
erythroid-specific isoform precursor, DNA-sequence determination
486848
65000 - 70000
-
-
486817
68000
-
gel filtration
486810
70000
-
mitochondrial enzyme, cytosolic enzyme is a precursor of the mitochondrial enzyme
486816
76000
-
precursor form, gel filtration
486838
77000
-
mitochondria, gel filtration
486843
80000
-
active form, gel filtration
486829
81000
-
gel filtration
486819
87000
-
gel filtration
486832
87000
-
gel filtration
486839
93000
-
gel filtration
486835
97000
-
gel filtration
486839
100000
-
inactive form, gel filtration
486829
100000
-
enzyme I and II, gel filtration
486831
105000
-
enzyme I, gel filtration
486844
107000 - 110000
-
stripped form, sucrose density gradient centrifugation, gel filtration, disc gel electrophoresis
486837
110000
-
cytosolic enzyme, is a precursor of the mitochondrial enzyme
486816
110000
-
sucrose density gradient centrifugation, gel filtration
486834
110000
-
enzyme II, gel filtration
486844
112000
-
gel filtration
486852, 486853
115000
-
gel filtration
486814
118000
-
dimer, gel filtration
486822
120000
-
gel filtration
486833
158000
-
gel filtration
486860
178000
-
cytosol, gel filtration
486843
200000
-
gel filtration
486820
218000
-
tetramer of enzyme and native activator protein, gel filtration
486822
295000
-
gel filtration, presence of NaCl
486812
500000
-
gel filtration, absence of NaCl
486812
additional information
-
amino acid composition
486825
additional information
-
mitochondrial enzyme has a minimum MW of 70000 (SDS-PAGE) and is apparently synthesized as a larger precursor of minimum MW 76000
486838
additional information
-
amino acid sequence determination of the purified protein
486848
additional information
-
amino acid sequence alignment
486852
additional information
-
amino acid sequence alignment
486855
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 57000, SDS-PAGE
?
-
x * 49000, SDS-PAGE
?
-
x * 63000, about, SDS-PAGE
?
-
x * 68000, possibly degraded enzyme, SDS-PAGE
?
-
x * 49000, erythroid-specific isoform, SDS-PAGE
dimer
-
2 * 56000, SDS-PAGE
dimer
-
2 * 53000, SDS-PAGE
dimer
-
2 * 49000, SDS-PAGE
dimer
-
2 * 49000, SDS-PAGE
dimer
-
2 * 54000, SDS-PAGE
dimer
-
2 * 51000, cytosol, SDS-PAGE
dimer
-
2 * 56000, mouse enzyme expressed in Escherichia coli, SDS-PAGE
dimer
-
2 * 62200, SDS-PAGE
dimer
-
2 * 58000, mitochondria, SDS-PAGE
monomer
-
1 * 57000, SDS-PAGE
monomer
-
1 * 61000-65000
additional information
-
the active site is located at the subunit interface and contains catalytically essential residues from the two subunits
additional information
-
splice variant lacking exon 4-encoded sequence produces a functional enzyme with slightly reduced activity compared to full-length enzyme. Interaction of both full-length enzyme and splice variant lacking exon 4-encoded sequence with succinyl CoA synthase
additional information
-
three-dimensional structural model of enzyme, comparison with human enzyme
additional information
-
three-dimensional structural model of enzyme, comparison with Rhodobacter sphaeroides enzyme. Mapping of a range of human mutants that give rise to X-linked sideroblastic anemia
additional information
P13196
two heme-binding motifs in the leader sequence, as well as one present in the N-terminus of the mature enzyme, function in vivo in the heme-regulated translocation of enzyme
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
first 49 amino acids of enzyme pre-protein are mitochondrial targeting sequence
ubiquitinylation
-
ALAS2 appears to be ubiquitinated as rapidly as at is produced
additional information
P13196
two heme-binding motifs in the leader sequence, as well as one present in the N-terminus of the mature enzyme, function in vivo in the heme-regulated translocation of enzyme
additional information
-
ALAS2 is hydroxylated under normoxic conditions
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion, crystal structure of full-length homodimeric enzyme binding its cofactor pyridoxal 5'-phosphate at 2.1 A, and structures of the enzyme in complex with the substrates glycine or succinyl-coenzyme A at 2.7 A and 2.8 A, respectivel
P18079
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.8 - 8
-
unstable below pH 6.8 and above pH 8.0, irreversible loss of activity
486812
9
Q6RVB3
retains about 80% of activity
661787
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
60 min, 20% loss of activity with addition of 2-mercaptoethanol and glycerol, 60% loss of activity without addition of 2-mercaptoethanol and glycerol
486811
50
Q6RVB3
retains about 80% of activity
661787
additional information
-
room temperature, inactivation within 30 min
486809
additional information
-
-
486820
additional information
-
temperature insensitive
486820
additional information
-
-
486823
additional information
-
thermal stability of glycine-rich motif mutants is reduced compared to the wild-type
486851
additional information
-
-
486851
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
enzyme is susceptible to proteolytic degradation during isolation, tendency to form aggregates
-
holoenzyme is more stable than apoenzyme
-
pyridoxal 5'-phosphate stabilizes
-
enzyme is susceptible to proteolytic degradation during isolation, tendency to form aggregates
-
partially purified enzyme requires high cation concentration, equivalent to 0.3 M NaCl for maximum stabilization
-
short half-life
-
freezing and thawing: precipitation and loss of activity
-
holoenzyme is more stable than apoenzyme
-
pyridoxal 5'-phosphate stabilizes
-
stable to freezing and thawing
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
ALAS2 is broken down under normoxic conditions by the proteasome
-
671812
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15C, 20 mM potassium phosphate buffer, pH 7.6, 1 mM dithioerythritol, 0.01 mM pyridoxal 5'-phosphate, 30% loss of activity after 2 weeks
-
-195C, following an initial loss of 20% of activity due to freeze-thawing the enzyme loses no further activity for at least 6 months
-
4C, 20 mM potassium phosphate buffer, pH 7.6, 1 mM dithioerythritol, 0.01 mM pyridoxal 5'-phosphate, 20% loss of activity after 2 weeks
-
4C, 50 mM Tris-HCl, 100 mM glycine, 0.1 mM pyridoxal 5'-phosphate, 1 mM dithioerythritol, pH 7.6, 5 mM 5'-AMP, stable for at least 4 months
-
4C, 30 min, 50% loss of apoenzyme of Protaminobacter ruber
-
-15C, loss of 25% activity within 10 days
-
-195C, following an initial loss of 20% of activity due to freeze-thawing the enzyme loses no further activity for at least 6 months
-
-20C, 20% loss of activity after 1 month
-
4C, 50 mM Tris-HCl, 100 mM glycine, 0.1 mM pyridoxal 5'-phosphate, 1 mM dithioerythritol, pH 7.6, 5 mM 5'-AMP, stable for at least 4 months
-
4C, loss of 40% activity within 10 days
-
-15C, 0.1 mM pyridoxal 5'-phosphate, 10% glycerol, 20% loss of activity after 6 weeks
-
-15C, 50 mM phosphate buffer, pH 6.8, 10% glycerol, 1 mM 2-mercaptoethanol, stable for several months
-
4C, 50 mM phosphate buffer, pH 6.8, 10% glycerol, 1 mM 2-mercaptoethanol, 10% loss of activity after 2 weeks
-
5C, 50 mM phosphate buffer, pH 7.2, 10 mM 2-mercaptoethanol, 20% loss of activity after 1 week
-
-15C, not stable
-
0-4C, 18 h stable
-
-30C, complete loss of activity overnight
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partial
-
recombinant from E. coli
-
recombinant of His-tagged wild-type and mutants from E. coli
-
recombinant wild-type and Lys313 mutants from Escherichia coli
-
recombinant wild-type and mutants from E. coli
-
high activity in cells grown anaerobically in defined medium, low in cells grown in an iron-deficient medium and in cells grown aerobically
-
partial purification, 2 isozymes
-
2 forms: a complex form and a stripped form that represents a catalytically active protein component of the complex form
-
difficulties due to the tendency of the enzyme to form large MW aggregates and to its susceptibility to proteolytic degradation
-
erythroid-specific isoform from reticulocytes, papain digestion method
-
partial, fetal enzyme
-
2 forms from low-iron medium
-
activator protein
-
isoforms I and II
-
2 isoenzymes: A and B
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
-
expression in Oryza sativa
-
expression in Escherichia coli
-
cDNA from erythroid genetic library
-
expressed in eukaryotic cells
-
liver and erythroid enzyme
-
expressed in Escherichia coli
-
expression of erythroid-specific isoform ALAS-E and mutants in Escherichia coli
-
expression of erythroid-specific isoform in MEL mutant under control of metallothionin promotor
-
expression of His-tagged wild-type, mutant K313A, mutant R149A and dimer mutant K313A/R149A, each subunit from 1 plasmid, in Escherichia coli hemA- mutant
-
expression of wild-type and mutants in Escherichia coli
-
overexpression of His-tagged wild-type and mutants in Escherichia coli
-
overexpression of mouse erythroid enzyme in Escherichia coli
-
transient expression of erythroid-specific isoform and promotor-mutant in HeLa cells, luciferase reporter gene
-
expression in Escherichia coli
-
erythroid-specific isoform ALAS-E, DNA-sequencing and sequence analysis, amino acid sequence determination of precursor protein
-
liver enzyme
-
expression in Escherichia coli
P18079
expression in Escherichia coli
-
fusion protein of enzyme and plastid-targeting small subunit of ribulose bisphosphate carboxylase for construction of transgenic plants
-
gene hem, functional complementation of Saccharomyces cerevisiae hem1 mutant
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the relative expression of ALAS1 mRNA, the first and rate-limiting enzyme for heme biosynthesis under normal physiological conditions, is significantly reduced by nearly 90% in patients with Alzheimer's disease compared to control. The relative expression of porphobilinogen deaminase mRNA, the third enzyme in the heme synthesis pathway and a secondary rate-limiting enzyme in heme biosynthesis, is also significantly reduced by nearly 60% in brain of patients with Alzheimer's disease and significantly related to apolipoprotein E genotype. The relative expression of aminolevulinate dehydratase mRNA, the second and a non-rate-limiting enzyme for heme biosynthesis, is unchanged between the two groups
-
HIF1R knockdown by RNA interference decreased the level of ALAS2 expression. In silico analysis reveal three potential hypoxia-response elements (HREs) that are located 611, 621, and 741 bp downstream of the ALAS2 gene
-
analysis of the 5' regulatory region of 5-aminolevulinate synthase gene in variegate porphyria patients heterozygous for the causative R59W mutation in the protoporphyrinogen oxidase gene. In the presence of estrogen and ERalpha, the wild-type -853C/-1253T allele induces a 47% increase in transcription, while the -853T/-1253A double mutant allele showed a 35% increase in transcription. The highest induction is observed for the mutant -853T/1253T allele generating an increase of 66%
-
increased expression of erythroid specific 5-aminolevulinate synthase ALAS2 and gamma-globin mRNAs after 48 h of hypoxia. Exogenous TGF-beta1 induces hemoglobinization and the expression of ALAS2 mRNA in YN-1-0-A cells, but not of c-globin and mitoferrin mRNAs. A specific inhibitor of intracellular TGF-b signaling markedly reduces the degree of the hypoxia-mediated increase in the expression of ALAS2 mRNA in YN-1-0-A cells
-
under hypoxic conditions, significantly increased ALAS2 mRNA and protein levels are detected in K562 cells and erythroid induction cultures of CD34+ hematopoietic stem/progenitor cells
-
in mouse model of erythropoietic protoporphyria, isoflurane induces 5-aminolevulinate synthase activity and increases excretion of porphyrin precursors
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A425G/Y428H/R433H/G434N/E435K/L437K
-
hexa variant, kcat increased compared to wild-type, Km (Gly) comparable to wild-type, Km (succinyl-CoA) decreased compared to wild-type
A425T
-
single variant, kcat slightly increased compared to wild-type, Km (Gly) comparable to wild-type, Km (succinyl-CoA) decreased compared to wild-type
L437Q
-
single variant, kcat comparable to wild-type, Km (Gly) comparable to wild-type, Km (succinyl-CoA) decreased compared to wild-type
N427H
-
single variant, kcat slightly increased compared to wild-type, Km (Gly) comparable to wild-type, Km (succinyl-CoA) decreased compared to wild-type
R433K/G434K/E435Q/L437Q
-
quadruple variant, kcat increased compared to wild-type, Km (Gly) comparable to wild-type, Km (succinyl-CoA) decreased compared to wild-type
V423I/A425P/Y428C/P432R/R433K/E435N
-
hexa variant, kcat increased compared to wild-type, Km (Gly) comparable to wild-type, Km (succinyl-CoA) decreased compared to wild-type
V423L/Y428R/P432E/R433I/G434N/E435Q/L437K
-
hepta variant, kcat increased compared to wild-type, Km (Gly) comparable to wild-type, Km (succinyl-CoA) decreased compared to wild-type
Y428I/R433Q /G434N/E435T/L437N
-
penta variant, kcat increased compared to wild-type, Km (Gly) comparable to wild-type, Km (succinyl-CoA) decreased compared to wild-type
Y428N/P432N/R433I/G434E/E435K/L437K
-
hexa variant, kcat increased compared to wild-type, Km (Gly) comparable to wild-type, Km (succinyl-CoA) decreased compared to wild-type
S568G
-
mutant shows decreased catalytic activity in vitro (20% compared to wild-type), but a higher half-life compared to those of wild-type ALAS2
V562A
-
mutant shows a higher catalytic activity in vitro, but a shorter half-life in vivo compared to those of wild-type ALAS2
D279A
-
exchange mutant of potential cofactor binding residue Asp279, no activity, dissociation constant for pyridoxal 5'-phosphate is 19fold increased, different mode of cofactor binding, no formation of quinonoid reaction intermediate, which can be restored by addition of analogue N-methyl-pyridoxal 5'-phosphate
D279E
-
exchange mutant of potential cofactor binding residue Asp279, 30fold reduced catalytic efficiency for succinyl-CoA compared to the wild-type
G142C
-
glycine-rich motif mutant, 15fold increased dissociation constant value for binding of cofactor pyridoxal 5'-phosphate, 6% turnover compared to the wild-type, 4fold increase of Km-value for glycine
G144A
-
glycine-rich motif mutant, 8.5fold increased dissociation constant value for binding of cofactor pyridoxal 5'-phosphate, 43% turnover compared to the wild-type, unaltered Km-values for the substrates
G144S
-
glycine-rich motif mutant, 8fold increased dissociation constant value for binding of cofactor pyridoxal 5'-phosphate, 39% turnover compared to the wild-type, unaltered Km-values for the substrates
G144T
-
glycine-rich motif mutant, 24.5fold increased dissociation constant value for binding of cofactor pyridoxal 5'-phosphate, 21% turnover compared to the wild-type, unaltered Km-values for the substrates
K313A
-
mutation site located at the active site of 1 subunit, functional complementation of Escherichia coli mutant strain hemA-, no activity
K313A
-
site-directed mutagenesis, mutants of erythroid-specific isoform, exchange of active site lysine residue 313, binding of pyridoxal 5'-phosphate and glycine noncovalently, reduced activity, because covalent binding is required
K313A/R149A
-
each mutation site located on 1 subunit, 2 plasmids, coexpression of the dimer in Escherichia coli hemA-, functional complementation, 26% activity compared to wild-type
K313G
-
site-directed mutagenesis, mutants of erythroid-specific isoform, exchange of active site lysine residue 313, binding of pyridoxal 5'-phosphate and glycine noncovalently, reduced activity, because covalent binding is required
K313H
-
site-directed mutagenesis, mutants of erythroid-specific isoform, exchange of active site lysine residue 313, binding of pyridoxal 5'-phosphate and glycine noncovalently, reduced activity, because covalent binding is required
K313H
-
formation of quinonoid reaction intermediates
R149A
-
mutation site located at the active site of 1 subunit, functional complementation of Escherichia coli mutant strain hemA-, no activity
R433K
-
active site mutant, 2fold increased activity
R433L
-
active site mutant, similar to the wild-type
R439K
-
active site mutant, 77% activity compared to the wild-type, 9-13fold increased Km for both substrates, 5fold increased dissociation constant for glycine
R439L
-
active site mutant, no activity, 30fold increased dissociation constant for glycine
R85K
-
catalytic efficiency similar to wild-type
R85L
-
68fold increase in catalytic efficincy with substrate octanoyl-CoA
R85L/T430V
-
strong decrease in catalytic efficiency
S254A
-
increase in Km value for succinyl-Coa and kcat value. Removal of the side chain hydroxyl group alters the microenvironment of the PLP cofactor and hinders succinyl-CoA binding
S254T
-
decrease in kcat value without altering Km value
Y121F
-
exchange mutant of potential cofactor binding residue Tyr121, 5% activity compared to the wild-type, Km for glycine is 5fold increased, lower affinity for pyridoxal 5'phosphate
Y121H
-
exchange mutant of potential cofactor binding residue Tyr121, 36% activity compared to the wild-type, Km for glycine is 34fold increased, lower affinity for pyridoxal 5'phosphate
N157Y/N162S
-
mutant strain G101, lacks enzyme activity, but can complement mutant strain G220 with mutation T452R
M567I
-
mutant shows 25% of wild-type activity, while its half-life is longer than that of wild-type
additional information
-
analysis of the 5' regulatory region of 5-aminolevulinate synthase gene in variegate porphyria patients heterozygous for the causative R59W mutation in the protoporphyrinogen oxidase gene. In the presence of estrogen and ERalpha, the wild-type -853C/-1253T allele induces a 47% increase in transcription, while the -853T/-1253A double mutant allele showed a 35% increase in transcription. The highest induction is observed for the mutant -853T/1253T allele generating an increase of 66%
additional information
-
the deletion of 33 amino acids at C-terminal end results in higher catalytic activity both in vitro and in vivo with the longer half-life compared to wild-type
K313R
-
formation of quinonoid reaction intermediates
additional information
-
site-directed mutagenesis of hypoxia-inducible factor-1, i.e. HIF-1, binding site in promotor sequence -328/-318, reveales HIF-1 like activation of enzyme expression during hypoxia
additional information
-
stable MEL mutant, no induction of enzyme expression by dimethylsulfoxide, hexamethylene diacetamide and butyric acid, decline of enzyme activity after DMSO application, expression of erythroid-specific isoform in MEL mutant under control of metallothionin promotor results in induction of enzyme activity by addition of Zn2+ and Cd2+ in absence of DMSO
additional information
-
circularly permuted enzyme variants with N-terminal amino acids corrosponding to L25, Q69, N404, N408 and a monomeric protein consisting of two wild-type enzyme subunits covalently linked through the N-terminus of one subunit to the C-terminuns of the other. Analysis of guanidine hydrochloride-induced unfolding, conformational stability, and structure
additional information
-
linkage of two subunits into a single polypeptide chain dimer 2XALAS, results in enzyme with about 7fold greater turnover number than wild-type and with greater A410/A330 ratio
additional information
-
a single chain dimeric ALAS variant is created, in which one of the two active sites harbors a K313A mutation eliminating measurable enzyme activity in order to investigate the unusual enhanced enzymatic activity resulting from linking ALAS dimmers. The two active sites in ALAS/ALAS differentially contribute to the enhanced activity of the enzyme, even though the amount of ALA produced during the first turnover is identical in both active sites. The kcat values of the K313A variants differ significantly depending on which of the two active sites harbors the mutation
C145R
-
mutant strain G205, lacks enzyme activity, but can complement mutant strain Ole3 with mutation G344C
additional information
-
construction of transgenic plants of Nicotiana tabacum wild-type and mutant deficient in chlorophyll biosynthesis expressing the enzyme targeted to the plastids, functional complementation of the mutant, regulation
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
complete reversibility of guanidine hydrochloride-induced unfolding
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
-
by expression in Escherichia coli Rosetta and combining D-xylose as a inhibitor for 5-aminolevulinate dehydratase with D-glucose in fed-batch culture and based on the optimal culture system, the yield of 5-aminolevulinate achieved is 7.3 g/l or 56 mM under the appropriate conditions
synthesis
-
in Escherichia coli expressing 5-aminolevulinate synthase, increasing D-glucose concentration in culture enhances final cell density and 5-aminolevulinate yield and simultaneously decreases the activities of 5-aminolevulinate synthase and 5-aminolevulinate dehydratase. The inhibitory effect of D-glucose on 5-aminolevulinate synthase activity is relieved with the metabolism of D-glucose. A final extracellular 5-aminolevulinate concentration of 3.1 g/l can be reached by feeding with D-glucose
agriculture
-
with high irradiance, transgenic rice lines P5 and P14 expressing 5-aminolevulinate synthase show a decrease in contents of chlorophyll and the chloroplast-encoded gene psbA mRNA, whereas a decrease in light-harvesting Chl-binding proteins is observed only in P14. These effects are not observed in the wild-type or all of the lines treated with low irradiance. High irradiance results in a greater decrease in the quantum yield of photosystem 2 and a greater increase in nonphotochemical quenching in the transgenic lines, particularly in P14. Photoprotective zeaxanthin contents increase at high irradiance, even though carotenoid contents are lower in the transgenic lines. When exposed to high irradiance, superoxide dismutase greatly increased in transgenic lines P5 and P14, but peroxidase and glutathione reductase increases only in P14, in which more photodynamic damage occurrs
synthesis
-
production of 5-aminolevulinic acid by a genetic engineering. As glycine and succinate are inexpensive, the enzymatic production of 5-aminolevulinic acid from glycine and succinate might be an attractive process
medicine
-
three-dimensional structural model of enzyme, mapping of a range of human mutants that give rise to X-linked sideroblastic anemia
medicine
-
hypoxia induces the expression of TGF-beta1 and mitoferrin mRNAs through separate mechanisms in erythroid cells. TGF-beta1 subsequently induces erythroidspecific 5-aminolevulinate synthase ALAS2 expression
medicine
-
the relative expression of ALAS1 mRNA, the first and rate-limiting enzyme for heme biosynthesis under normal physiological conditions, is significantly reduced by nearly 90% in patients with Alzheimer's disease compared to control. The relative expression of porphobilinogen deaminase mRNA, the third enzyme in the heme synthesis pathway and a secondary rate-limiting enzyme in heme biosynthesis, is also significantly reduced by nearly 60% in brain of patients with Alzheimer's disease and significantly related to apolipoprotein E genotype. The relative expression of aminolevulinate dehydratase mRNA, the second and a non-rate-limiting enzyme for heme biosynthesis, is unchanged between the two groups
medicine
-
in mouse model of erythropoietic protoporphyria, isoflurane induces 5-aminolevulinate synthase activity and increases excretion of porphyrin precursors. Mice homozygotically lacking ferrochelatase activity and receiving anaestesia show enhanced 5-aminolevulinate synthase and Cyp2E1 activities in the liver and increased urinary excretion of porphyrin precursors
pharmacology
-
enzyme is a target for drug development because of its immunological and inhibitor specificity
biotechnology
-
Propionibacterium acidipropionici TISTR442 produce the highest amount of 5-aminolevulinic acid (ALA) when cultivated in medium supplemented with glycine at 18 g/l. This optimal condition for ALA production via the addition of glycine provides an easy and low-cost technique for themass cultivation of Propionibacterium acidipropionici
synthesis
-
optimization of recombinant aminolevulinate synthase production using factorial design. Initial succinate, glucose, and IPTG concentration are key factors affecting enzyme activity. Fermentation yields up to 5.2 g/l 5-aminolevulinate
synthesis
-
production of 5-aminolevulinate by recombinant Escherichia coli. Terrific broth medium results in significantly higher cell growth and 5-aminolevulinate production than Luria-Bertani medium. 5-Aminolevulinate production is significantly enhanced by the addition of succinate together with glycine in the medium. Maximal 5-aminolevulinate production of 2.5 g/l is observed upon the addition of D-glucose as an 5-aminolevulinate dehydratase inhibitor in the late-log culture phase and maintenance of a pH value of 6.5
nutrition
-
enzyme expressed in transgenic Nicotiana tabacum plants demonstrate functional complementation in the chlorophyll biosynthesis and open strategies for producing tolerance against inhibitors of the C5 pathway