Information on EC 4.99.1.1 - ferrochelatase

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

EC NUMBER
COMMENTARY hide
4.99.1.1
-
RECOMMENDED NAME
GeneOntology No.
ferrochelatase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
protoheme + 2 H+ = protoporphyrin + Fe2+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
elimination
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
heme biosynthesis I (aerobic)
-
-
heme biosynthesis II (anaerobic)
-
-
superpathway of heme biosynthesis from uroporphyrinogen-III
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-
heme metabolism
-
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Porphyrin and chlorophyll metabolism
-
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Metabolic pathways
-
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Biosynthesis of secondary metabolites
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SYSTEMATIC NAME
IUBMB Comments
protoheme ferro-lyase (protoporphyrin-forming)
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CAS REGISTRY NUMBER
COMMENTARY hide
9012-93-5
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
chironomid larvae
SwissProt
Manually annotated by BRENDA team
strain CC124
SwissProt
Manually annotated by BRENDA team
strain CC124
SwissProt
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
zebrafish
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
var. PI 177418
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Rhizopus oryzae RA 99-880
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
Uniprot
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
-
siRNA-mediated knockdown of ferrochelatase suppresses heme synthesis and significantly increases intracellular protoporphyrin IX (PpIX) accumulation, this improves the phototoxicity of 5-aminolevulinic acid-based photodynamic therapy in urothelial cancer cell lines
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2,4-disulfonic deuteroporphyrin + Fe2+
?
show the reaction diagram
-
-
-
?
Cd2+-protoporphyrin + H+
protoporphyrin + Cd2+
show the reaction diagram
-
poor substrate
-
-
?
Co2+-protoporphyrin + H+
protoporphyrin + Co2+
show the reaction diagram
-
-
-
-
?
deuteroporphyrin + Fe2+
deuteroheme + H+
show the reaction diagram
deuteroporphyrin + Fe2+
protoheme + H+
show the reaction diagram
-
-
-
-
-
deuteroporphyrin + Mn2+
? + H+
show the reaction diagram
-
in contrast to protoporphyrin IX, deuteroporphyrin lacks the vinyl groups at the 2- and 4-ring positions, and therefore, it is possible to structurally discriminate enzyme-bound (metallated) deuteroporphyrin from any possible heme (protoheme) carryover from the enzyme preparation
-
-
?
deuteroporphyrin + Ni2+
? + H+
show the reaction diagram
-
the Ni-deuteroporphyrin structure is distinctly different from the Mn-deuteroporphyrin model, despite the only variation in enzyme preparation being the addition of either Ni or Mn
-
-
?
deuteroporphyrin IX + Zn2+
Zn deuteroporphyrin IX + H+
show the reaction diagram
-
in vitro, zinc is the preferred substrate at all concentrations of porphyrin
-
-
?
deuteroporphyrin IX + Zn2+
Zn-deuteroporphyrin IX + H+
show the reaction diagram
Fe2+-2,4-bis-acetal deuteroporphyrin
?
show the reaction diagram
-
-
-
-
?
Fe2+-2,4-diacetyldeuteroporphyrin
?
show the reaction diagram
-
-
-
-
?
Fe2+-2,4-disulfonate deuteroporphyrin
?
show the reaction diagram
-
-
-
-
?
Fe2+-hematoporphyrin
?
show the reaction diagram
Fe2+-mesoporphyrin IX + H+
mesoporphyrin IX + Fe2+
show the reaction diagram
-
-
-
-
?
Fe2+-protoporphyrin + H+
protoporphyrin + Fe2+
show the reaction diagram
-
-
-
-
?
heme + Zn2+
Zn-protoporphyrin + H+
show the reaction diagram
-
-
-
-
?
hemin + H+
mesoporphyrin IX + Zn2+
show the reaction diagram
-
-
-
-
r
hemoglobin + Zn2+
Zn-protoporphyrin + H+
show the reaction diagram
mesoporphyrin + Fe2+
mesoheme
show the reaction diagram
pH 8.0
-
-
?
mesoporphyrin + Fe2+
mesoheme + H+
show the reaction diagram
mesoporphyrin + Zn2+
mesoheme
show the reaction diagram
-
37C
-
-
?
mesoporphyrin + Zn2+
Zn-mesoporphyrin + H+
show the reaction diagram
-
-
-
-
?
mesoporphyrin IX + Fe2+
?
show the reaction diagram
mesoporphyrin IX + Fe2+
mesoheme IX + H+
show the reaction diagram
mesoporphyrin IX + Fe2+
protoporphyrin IX + H+
show the reaction diagram
-
-
-
-
?
mesoporphyrin IX + ferrous ammonium sulfate
mesoheme + ammonium sulfate
show the reaction diagram
-
room temperature
-
-
?
mesoporphyrin IX + Zn2+
hemin + H+
show the reaction diagram
-
-
-
-
r
myoglobin + Zn2+
Zn-protoporphyrin + H+
show the reaction diagram
N-methyl mesoporphyrin + Cu2+
?
show the reaction diagram
-
pH 7.4
-
-
?
N-methyl mesoporphyrin + Zn2+
?
show the reaction diagram
-
pH 7.4
-
-
?
porphyrin + Fe2+
heme + H+
show the reaction diagram
-
-
-
-
?
porphyrin + metal ion
metalloporphyrin
show the reaction diagram
protoheme + H+
protoporphyrin + Fe2+
show the reaction diagram
protoporphyrin + Cu2+
Cu2+-protoporphyrin + H+
show the reaction diagram
-
-
-
?
protoporphyrin + Fe2+
protoheme + 2 H+
show the reaction diagram
protoporphyrin + Fe2+
protoheme + H+
show the reaction diagram
protoporphyrin + Zn2+
Zn2+-protoporphyrin + H+
show the reaction diagram
protoporphyrin IX + Co2+
Co2+-protoporphyrin + H+
show the reaction diagram
-
-
-
-
?
protoporphyrin IX + Cu2+
Cu2+-protoporphyrin + H+
show the reaction diagram
-
Cu2+ is a good substrate
-
-
?
protoporphyrin IX + Fe2+
?
show the reaction diagram
protoporphyrin IX + Fe2+
heme + H+
show the reaction diagram
-
-
-
?
protoporphyrin IX + Fe2+
protoheme + H+
show the reaction diagram
protoporphyrin IX + Fe2+
protoheme IX + H+
show the reaction diagram
protoporphyrin IX + FeCl3
protoheme + HCl
show the reaction diagram
pH 7.5, 37C
-
-
-
protoporphyrin IX + Ni2+
?
show the reaction diagram
-
-
-
-
?
protoporphyrin IX + Zn2+
?
show the reaction diagram
-
-
-
?
protoporphyrin IX + Zn2+
Zn protoporphyrin IX
show the reaction diagram
-
pH 7.4, room temperature
-
-
?
protoporphyrin IX + Zn2+
Zn-protoporphyrin + H+
show the reaction diagram
-
-
-
-
?
protoporphyrin IX + Zn2+
Zn-protoporphyrin IX
show the reaction diagram
protoporphyrin IX + Zn2+
Zn-protoporphyrin IX + H+
show the reaction diagram
-
-
-
-
?
protoporphyrin IX + Zn2+
Zn2+-protoporphyrin IX + H+
show the reaction diagram
-
-
-
-
?
Sn2+-protoporphyrin + H+
protoporphyrin + Sn2+
show the reaction diagram
-
-
-
-
?
Zn2+-mesoporphyrin + H+
mesoporphyrin + Zn2+
show the reaction diagram
Zn2+-protoporphyrin + H+
protoporphyrin + Zn2+
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
protoheme + H+
protoporphyrin + Fe2+
show the reaction diagram
protoporphyrin + Fe2+
protoheme + 2 H+
show the reaction diagram
protoporphyrin + Fe2+
protoheme + H+
show the reaction diagram
protoporphyrin IX + Fe2+
?
show the reaction diagram
protoporphyrin IX + Fe2+
protoheme IX + H+
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
heme
-
-
[2Fe-2S]-center
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
absolute requirement
Hg2+
-
human ferrochelatase is capable of catalyzing the insertion of the inhibitory metal ion Hg2+ into a porphyrin macrocycle
Pb2+
0.1 mM, reduces the enzymatic activity by more than 60%
Sn2+
-
-
[2Fe-2S]cluster
additional information
-
no [2Fe-2S] cluster
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,2'-dipyridyl
-
-
deferoxamine
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-
deuteroporphyrin IX
-
-
Divalent cations
-
-
-
Fe2+
-
Zn2+-chelatase activity
iodacetic acid
-
-
iodoacetamide
metalloporphyrin
-
containing Fe2+, Co2+, Zn2+, Sn2+
-
Metalloporphyrins
-
-
-
Mg2+
0.1 mM, reduces the enzymatic activity by more than 60%
Mg2+-protoporphyrin
-
-
monobromobimane
-
-
N-alkylated porphyrins
-
N-ethylmaleimide
N-methyl mesoporphyrin
-
transition-state inhibitor
N-methylmesoporphyrin
-
N-Methylprotoporphyrin
N-methylprotoporphyrin IX
-
Ni2+
-
substrate inhibition occurs when assayed in the absence of metal ion-complexing buffer components
p-chloromercuribenzoate
-
-
porphyrin
-
high porphyrin concentrations noticeably increase the extent of zinc inhibition
porphyrin isomer
-
competitive
-
Porphyrins
protohaem
-
-
-
sulfhydryl reagents
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ascorbate
Cu2+
0.1 mM, causes 4fold increase in activity
L-cysteine
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.056
2,4-bisacetal deuteroporphyrin
-
-
-
0.479
2,4-diacetyldeuteroporphyrin
-
-
-
0.052
2,4-disulfonic deuteroporphyrin
-
-
-
0.0052 - 0.56
Co2+
0.063 - 0.17
Cu2+
0.0213
deuteroporphyrin
-
-
0.0026 - 0.0461
deuteroporphyrin IX
0.00048 - 0.166
Fe2+
0.055
hematoporphyrin
-
-
0.0057
Hemin
-
pH 5.5, 45C
0.004 - 0.1
mesoporphyrin
0.0047 - 0.0302
mesoporphyrin IX
0.012
Myoglobin
-
at pH 6.5 and 30C
-
0.02206 - 0.1037
Ni2+
0.0121 - 0.0246
porphyrin
0.002 - 0.05
protoporphyrin
0.00022 - 0.116
protoporphyrin IX
0.00017 - 0.06
Zn2+
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.016 - 0.033
Co2+
0.065
Cu2+
Bacillus subtilis
-
wild type enzyme, in 100 mM tris(hydroxymethyl)aminomethane-HCl, pH 7.4, temperature not specified in the publication
0.018 - 0.3
Fe2+
0.52
Hemin
Sus scrofa
-
pH 5.5, 45C
6.7
mesoporphyrin IX
Sus scrofa
-
pH 8.0, 37C
0.01167 - 0.0573
porphyrin
0.3 - 0.483
protoporphyrin
Bacillus subtilis
-
-
0.0125 - 1.9
protoporphyrin IX
0.034 - 6.7
Zn2+
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
76 - 1200
deuteroporphyrin IX
6244
62.5 - 416.8
Fe2+
25
0.000092
Hemin
Sus scrofa
-
pH 5.5, 45C
822
0.00101
mesoporphyrin IX
Sus scrofa
-
pH 8.0, 37C
2159
0.56 - 9.05
Ni2+
38
47.3 - 2015
protoporphyrin IX
868
0.00525 - 19000
Zn2+
14
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0712 - 0.3376
deuteroporphyrin IX
0.0014 - 0.00251
N-Methylprotoporphyrin
0.007 - 2.4
Ni2+
additional information
additional information
-
Ki-values of porphyrin isomers that are not substrates are in the range of 0.013-0.07 mM, Ki-values of metalloporphyrin isomers that are not substrates are in the range of 0.002-0.013 mM, Ki-values for metal inhibitors are in the range of 0.01-0.05 mM
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0015
-
at pH and C
0.033
-
R31G, pH 7.6, 30C, unaerobic conditions
0.041
-
wild-type, pH 7.6, 30C, unaerobic conditions
0.054
-
mutant T302A, pH 7.6, 30C, unaerobic conditions
0.056
-
mutant D76G/K102T, pH 7.6, 30C, unaerobic conditions
0.065
-
M11V/G104A, pH 7.6, 30C, unaerobic conditions
0.067
-
mutant E61K, pH 7.6, 30C, unaerobic conditions
0.093
-
E61K/L185Q/G212D, pH 7.6, 30C, unaerobic conditions
0.413
-
-
15.2
-
pH 8.0, 37C
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 6
-
-
5.5
-
reverse reaction
5.5 - 6
-
pH optimum for zinc removal
7.3
-
etioplast
7.3 - 7.5
-
2 optima, pH 7.3-7.5, pH 8.0-8.2, deuteroheme formation
7.5 - 8
8 - 8.2
-
2 optima, pH 7.3-7.5, pH 8.0-8.2, deuteroheme formation
8.25
-
protoporphyrin
8.35
-
mesoporphyrin
8.45
-
deuteroporphyrin
additional information
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.3 - 8.6
-
-
6.8 - 8.3
-
-
6.8 - 9.5
-
-
7.2 - 8.8
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
18 - 37
-
Q10: 2.9 kcal/mol
55.8
-
Tm, wild-type in phosphate buffer
56
-
Tm, wild-type in bicine buffer
57.5
-
Tm, mutant E289A
61
-
Tm, mutant E289Q
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.12
predicted from amino acid sequence
7.35
-
isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
conversion of mesoporphyrin is dependent on the expression of ferrochelatase, since control Balb/3T3 cells have much lower expression of ferrochelatase than the ferrochelatase transfectants
Manually annotated by BRENDA team
-
splenic erythroblast
Manually annotated by BRENDA team
-
cultured
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
the recombinant protein expressed in Escherichia coli
Manually annotated by BRENDA team
-
preprotein with a cleavable presequence at its amino-terminus
Manually annotated by BRENDA team
additional information