Information on EC 3.4.24.18 - meprin A

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The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY
3.4.24.18
-
RECOMMENDED NAME
GeneOntology No.
meprin A
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Hydrolysis of protein and peptide substrates preferentially on carboxyl side of hydrophobic residues
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of amide bond
-
-
hydrolysis of arylamide bond
-
-
-
-
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E-24.18
-
-
-
-
EC 3.4.24.11
-
-
formerly included in
-
Endopeptidase-2
-
-
-
-
M12.002
-
-
Meprin
-
-
-
-
meprin A
-
-
meprin A metalloprotease
-
-
meprin A metalloprotease
-
-
meprin A metalloproteinase
-
-
meprin alpha
-
-
meprin alpha
Q16819
-
meprin alpha
-
-
meprin alpha1
Q5RHM1
-
meprin alpha2
B3DKP9
-
meprin beta
-
-
meprin metalloproteinase
-
-
Meprin-a
-
-
-
-
metalloprotease meprin A
-
-
mouse meprin alpha
-
-
N-Benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase
-
-
-
-
PABA peptide hydrolase
-
-
-
-
PABA-peptide hydrolase
-
-
-
-
PPH
-
-
-
-
PPH alpha
-
-
-
-
PPH beta
-
-
-
-
metalloprotease meprin A
-
-
additional information
-
meprin A from mouse, endopeptidase-2 from rat and PPH from human are closely related enzymes of the astacin family
CAS REGISTRY NUMBER
COMMENTARY
148938-24-3
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
patients with diabetes mellitus
-
-
Manually annotated by BRENDA team
Homo sapiens PPH
PPH
-
-
Manually annotated by BRENDA team
db/db mice lacking the hypothalamic leptin receptor, representing a model of type 2 diabetes mellitus
-
-
Manually annotated by BRENDA team
expression in HEK-293 cell
-
-
Manually annotated by BRENDA team
male ICR
-
-
Manually annotated by BRENDA team
meprin A, from male BALB/c
-
-
Manually annotated by BRENDA team
mouse, strain ICR and C3H/He
-
-
Manually annotated by BRENDA team
random bred ICR and at least 35 inbred, recombinant and congenic strains
-
-
Manually annotated by BRENDA team
Mus musculus male ICR
male ICR
-
-
Manually annotated by BRENDA team
endopeptidase-2, male Wistar
-
-
Manually annotated by BRENDA team
Sprague Dawley
-
-
Manually annotated by BRENDA team
treated with streptozocin, representing a model of type 1 diabetes mellitus
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
B3DKP9, Q5RHM1
knockdown of meprin alpah1 mRNA causes defects in general tissue differentiation
malfunction
B3DKP9, Q5RHM1
meprin alpha2 morphants show severe failures in the formation of the vascular system
malfunction
-
meprin inhibition elevates levels of natriuretic peptides in plasma and the vascular wall, decreases plaque volume and suppresses lipid deposition in carotid arteries, reduces production of reactive oxygen species and apoptosis (which are associated with atherosclerosis) in the vascular wall, and increases natriuretic peptide function on cell apoptosis, proliferation, and intracellular reactive oxygen species generation in the THP-1 cell line and primary vascular smooth muscle cells
physiological function
-
meprin A plays a role in the regulation of B-type natriuretic peptide 1-32 bioactivity in the kidney
physiological function
-
meprin beta induces a dramatic change in cell morphology and a significant reduction in cell number, whereas meprin alpha plays a role for basal keratinocyte proliferation in vitro
physiological function
-
meprin metalloproteases are important for cell differentiation and proliferation already during embryogenesis, predominantly by the activation of growth factors. Meprins play a significant role in vascular endothelial growth factor-A processing, subsequently regulating angiogenesis
physiological function
-
meprin metalloproteases are important for cell differentiation and proliferation already during embryogenesis, predominantly by the activation of growth factors. Meprins play a significant role in VEGF-A processing, subsequently regulating angiogenesis
physiological function
-
meprin-alpha is capable of increasing lipopolysaccharide-induced production of cytokines in peripheral blood mononuclear cells, which is associated with the activation of nuclear factor-kappaB
physiological function
-
meprins stimulate epithelial Na+ channel (ENaC) expressed exogenously in Xenopus oocytes and endogenously in epithelial cells. Co-expression of ENaC subunits and meprin beta or alpha/beta in Xenopus oocytes increases amiloride-sensitive Na+ currents 2fold. The meprin-mediated increase in ENaC currents in oocytes and epithelial cell monolayers requires meprin beta, but not the alpha subunit
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-aminobenzoic acid-RPPGFSPFRK(2,4-dinitrophenyl)G-OH + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-Arg-Gly-Pro-Phe-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Gly-Pro-Phe + Ser-Pro-(4-nitro)Phe-Arg
show the reaction diagram
-
fluorogenic bradykinin analog substrate, cleavage site: Phe-Ser
-
-
2-aminobenzoyl-Arg-Gly-Pro-Phe-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Gly-Pro-Phe + Ser-Pro-(4-nitro)Phe-Arg
show the reaction diagram
-
fluorogenic bradykinin analog substrate, cleavage site: Phe-Ser
-
-
2-aminobenzoyl-Arg-Hyp-Gly-Phe-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Hyp-Gly-Phe + Ser-Pro-(4-nitro)Phe-Arg
show the reaction diagram
-
fluorogenic bradykinin analog substrate, cleavage site: Phe-Ser
-
-
2-aminobenzoyl-Arg-Hyp-Gly-Phe-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Hyp-Gly-Phe + Ser-Pro-(4-nitro)Phe-Arg
show the reaction diagram
-
fluorogenic bradykinin analog substrate, cleavage site: Phe-Ser
-
-
2-aminobenzoyl-Arg-Pro-Gly-Ala-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly-Ala + Ser-Pro-(4-nitro)Phe-Arg
show the reaction diagram
-
fluorogenic bradykinin analog substrate, cleavage site: Ala-Ser
-
-
2-aminobenzoyl-Arg-Pro-Gly-Ala-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly-Ala + Ser-Pro-(4-nitro)Phe-Arg
show the reaction diagram
-
fluorogenic bradykinin analog substrate, cleavage site: Ala-Ser
-
-
2-aminobenzoyl-Arg-Pro-Gly-Glu-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly-Glu + Ser-Pro-(4-nitro)Phe-Arg
show the reaction diagram
-
fluorogenic bradykinin analog substrate, cleavage site: Glu-Ser
-
-
2-aminobenzoyl-Arg-Pro-Gly-Glu-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly-Glu + Ser-Pro-(4-nitro)Phe-Arg
show the reaction diagram
-
fluorogenic bradykinin analog substrate, cleavage site: Glu-Ser
-
-
2-aminobenzoyl-Arg-Pro-Gly-Leu-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly-Leu + Ser-Pro-(4-nitro)Phe-Arg
show the reaction diagram
-
fluorogenic bradykinin analog substrate, cleavage sites: Leu-Ser (major site) and Gly-Leu
major products
-
2-aminobenzoyl-Arg-Pro-Gly-Leu-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly-Leu + Ser-Pro-(4-nitro)Phe-Arg
show the reaction diagram
-
fluorogenic bradykinin analog substrate, cleavage sites: Leu-Ser (major site) and Gly-Leu
major products
-
2-aminobenzoyl-Arg-Pro-Gly-Lys-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly + Lys-Ser-Pro-(4-nitro)Phe-Arg
show the reaction diagram
-
fluorogenic bradykinin analog substrate, cleavage sites: Gly-Lys (major site) and Lys-Ser
major products
-
2-aminobenzoyl-Arg-Pro-Gly-Lys-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Gly + Lys-Ser-Pro-(4-nitro)Phe-Arg
show the reaction diagram
-
fluorogenic bradykinin analog substrate, cleavage sites: Gly-Lys (major site) and Lys-Ser
major products
-
2-aminobenzoyl-Arg-Pro-Ile-Phe-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Ile-Phe + Ser-Pro-(4-nitro)Phe-Arg
show the reaction diagram
-
fluorogenic bradykinin analog substrates, cleavage site: Phe-Ser
-
-
2-aminobenzoyl-Arg-Pro-Ile-Phe-Ser-Pro-(4-nitro)Phe-Arg + H2O
2-aminobenzoyl-Arg-Pro-Ile-Phe + Ser-Pro-(4-nitro)Phe-Arg
show the reaction diagram
-
fluorogenic bradykinin analog substrates, cleavage site: Phe-Ser
-
-
2-aminobenzoyl-RPPGFSPFRK-(dinitrophenyl)-G + H2O
?
show the reaction diagram
-
fluorogenic bradykinin analog substrate
-
?
Aldolase + H2O
?
show the reaction diagram
-
-
-
-
-
alpha-melanocyte stimulating hormone + H2O
?
show the reaction diagram
-
i.e. acetyl-Ser-Tyr-Ser-Met-Gly-His-Phe-Arg-Trp-Gly-Lys-Pro-Val, cleavage sites: Ser-Met, Gly-Lys, mouse
-
-
-
alpha-melanocyte stimulating hormone + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
alpha-MSH + H2O
?
show the reaction diagram
-
-
-
-
?
Angiotensin I + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
Angiotensin I + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe + Ile-His-Pro-Phe-His-Leu
show the reaction diagram
-
2 cleavage sites: Tyr-Ile and Phe-His
-
-
Angiotensin I + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe + Ile-His-Pro-Phe-His-Leu
show the reaction diagram
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu, cleavage site: Tyr-Ile
-
-
-
Angiotensin I + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe + Ile-His-Pro-Phe-His-Leu
show the reaction diagram
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu, cleavage site: Tyr-Ile
-
-
Angiotensin I + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe + Ile-His-Pro-Phe-His-Leu
show the reaction diagram
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu, cleavage site: Tyr-Ile
-
-
-
Angiotensin I + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe + Ile-His-Pro-Phe-His-Leu
show the reaction diagram
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu, cleavage site: Tyr-Ile
-
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
show the reaction diagram
-
poor substrate
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
show the reaction diagram
-
poor substrate
-
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
show the reaction diagram
-
cleavage site: Tyr-Ile
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
show the reaction diagram
-
cleavage site: Tyr-Ile
-
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
show the reaction diagram
-
cleavage site: Tyr-Ile
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
show the reaction diagram
-
cleavage site: Tyr-Ile
-
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
show the reaction diagram
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
show the reaction diagram
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
-
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
show the reaction diagram
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
-
-
Angiotensin II + H2O
Asp-Arg-Val-Tyr + Ile-His-Pro-Phe
show the reaction diagram
-
i.e. Asp-Arg-Val-Tyr-Ile-His-Pro-Phe
-
-
-
Angiotensin III + H2O
Arg-Val-Tyr + Ile-His-Pro-Phe
show the reaction diagram
-
poor substrate
-
-
Angiotensin III + H2O
Arg-Val-Tyr + Ile-His-Pro-Phe
show the reaction diagram
-
i.e. Arg-Val-Tyr-Ile-His-Pro-Phe, cleavage site: Tyr-Ile
-
-
-
Angiotensin III + H2O
Arg-Val-Tyr + Ile-His-Pro-Phe
show the reaction diagram
-
i.e. Arg-Val-Tyr-Ile-His-Pro-Phe, cleavage site: Tyr-Ile
-
-
Angiotensin III + H2O
Arg-Val-Tyr + Ile-His-Pro-Phe
show the reaction diagram
-
i.e. Arg-Val-Tyr-Ile-His-Pro-Phe, cleavage site: Tyr-Ile
-
-
-
annexin A1 + H2O
?
show the reaction diagram
-
substrate identified by 2D IEF/SDS-PAGE-based image analysis
-
-
?
Arg-Pro-Pro-Gly-(4-nitro)Phe-Ala-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Ala-Pro-Phe-Arg
show the reaction diagram
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Ala-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Ala-Pro-Phe-Arg
show the reaction diagram
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Arg-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Arg-Pro-Phe-Arg
show the reaction diagram
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Arg-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Arg-Pro-Phe-Arg
show the reaction diagram
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Lys-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Lys-Pro-Phe-Arg
show the reaction diagram
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Lys-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Lys-Pro-Phe-Arg
show the reaction diagram
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Phe-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Phe-Pro-Phe-Arg
show the reaction diagram
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Phe-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Phe-Pro-Phe-Arg
show the reaction diagram
-
chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Ser-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Ser-Pro-Phe-Arg
show the reaction diagram
-
i.e. nitrobradykinin, chromogenic bradykinin analog
-
-
Arg-Pro-Pro-Gly-(4-nitro)Phe-Ser-Pro-Phe-Arg + H2O
Arg-Pro-Pro-Gly-(4-nitro)Phe + Ser-Pro-Phe-Arg
show the reaction diagram
-
i.e. nitrobradykinin, chromogenic bradykinin analog
-
-
azocasein + H2O
?
show the reaction diagram
-
-
-
?
azocasein + H2O
fragments of azocasein
show the reaction diagram
-
-
-
-
-
azocasein + H2O
fragments of azocasein
show the reaction diagram
-
-
-
-
azocasein + H2O
fragments of azocasein
show the reaction diagram
-
excellent substrate for mouse, poorer substrate for rat and human enzymes
-
-
-
azocasein + H2O
fragments of azocasein
show the reaction diagram
-
better substrate for mouse enzyme than for rat enzyme
-
-
-
azocasein + H2O
fragments of azocasein
show the reaction diagram
Mus musculus male ICR
-
-
-
-
-
azocasein + H2O
fragments of azocasein
show the reaction diagram
Homo sapiens PPH
-
-
-
-
azocasein + H2O
fragments of azocasein
show the reaction diagram
Homo sapiens PPH
-
excellent substrate for mouse, poorer substrate for rat and human enzymes
-
-
-
Azocoll + H2O
?
show the reaction diagram
-
poor substrate
-
-
-
B-type natriuretic peptide + H2O
?
show the reaction diagram
-
meprin A degrades rat BNP but not human BNP
-
-
?
B-type natriuretic peptide 1-32 + H2O
B-type natriuretic peptide 8-32 + Ser-Pro-Lys-Met-Val-Gln-Gly
show the reaction diagram
-
-
-
-
?
benzoyl-Gly-His-Leu + H2O
?
show the reaction diagram
Homo sapiens, Homo sapiens PPH
-
very poor substrate, t1/2 of more than 16 h
-
-
-
Benzyloxycarbonyl-Arg-Arg 4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
Homo sapiens, Homo sapiens PPH
-
poor substrate, hydrolysis at 8.2% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
-
-
-
Benzyloxycarbonyl-Glu-Lys-Lys 4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
poor substrate, hydrolysis at 9.1% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
-
-
-
Benzyloxycarbonyl-Phe-Arg 4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
-
-
-
-
Benzyloxycarbonyl-Phe-Arg 4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
Homo sapiens, Homo sapiens PPH
-
poor substrate, hydrolysis at 3.6% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
-
-
-
Benzyloxycarbonyl-Val-Leu-Lys 4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
poor substrate, hydrolysis at 10.4% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
-
-
-
Big endothelin I + H2O
?
show the reaction diagram
-
rat
-
-
-
bombesin + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
show the reaction diagram
-
-
-
-
-
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
show the reaction diagram
-
-
-
-
-
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
show the reaction diagram
-
i.e. Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg, bradykinin(1-7) and bradykinin(1-8) best substrates next to substance P
-
-
-
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
show the reaction diagram
-
one cleavage site: Phe-Ser (major cleavage site)
-
-
-
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
show the reaction diagram
-
one cleavage site: Phe-Ser
-
-
-
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
show the reaction diagram
-
one cleavage site: Phe-Ser
-
-
-
bradykinin + H2O
Arg-Pro-Pro-Gly + Phe-Ser-Pro-Phe-Arg
show the reaction diagram
-
one cleavage site: Phe-Ser, minor cleavage site: Gly-Phe
-
-
-
Bradykinin + H2O
?
show the reaction diagram
-
-
-
?
Bradykinin + H2O
?
show the reaction diagram
-
-
-
-
?
Bradykinin + H2O
?
show the reaction diagram
-
-
-
?
Bradykinin + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
-
cerulein + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
cholecystokinin 8-sulfate + H2O
?
show the reaction diagram
-
-
-
?
collagen I + H2O
?
show the reaction diagram
-
-
-
?
Collagen IV + H2O
?
show the reaction diagram
-
-
-
?
Collagen IV + H2O
?
show the reaction diagram
-
-
-
-
?
Collagen type IV + H2O
Hydrolyzed collagen type IV
show the reaction diagram
-
-
-
-
collagen type IV + H2O
?
show the reaction diagram
-
meprin alpha can degrade collagen type IV
-
-
?
collagen type V + H2O
?
show the reaction diagram
-
substrate identified by 2D IEF/SDS-PAGE-based image analysis
-
-
?
Endothelin I + H2O
?
show the reaction diagram
-
rat
-
-
-
Fibronectin + H2O
?
show the reaction diagram
-
-
-
?
Fibronectin + H2O
?
show the reaction diagram
-
cleavage at positions Y294-Q295, N709-T210 and in the linker regions between fibronectin type I repeats 5 and 6 and fibronectin type II repeats 1 and 2
-
-
?
Fibronectin + H2O
Hydrolyzed fibronectin
show the reaction diagram
-
-
-
-
gastrin + H2O
?
show the reaction diagram
-
-
-
-
?
gastrin 17 + H2O
?
show the reaction diagram
-
mutant Y199K
-
?
Gelatin + H2O
Hydrolyzed gelatin
show the reaction diagram
-
-
-
-
Gelatin + H2O
?
show the reaction diagram
-
-
-
?
Glucagon + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
Glutaryl-Phe 4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
poor substrate, hydrolysis at 2.4% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
-
-
-
Gonadotropin + H2O
?
show the reaction diagram
-
mouse
-
-
-
GRP-(14-27) + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
Hemoglobin + H2O
?
show the reaction diagram
-
poor substrate
-
-
-
Human alpha-atrial natiuretic peptide + H2O
?
show the reaction diagram
-
-
-
-
-
Human alpha-atrial natiuretic peptide + H2O
?
show the reaction diagram
-
rat
-
-
-
Human transforming growth factor + H2O
?
show the reaction diagram
-
rat
-
-
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
show the reaction diagram
-
-
-
-
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
show the reaction diagram
-
I125-iodinated
-
-
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
show the reaction diagram
-
prevalent cleavage sites are Gly20-Glu21, Phe24-Phe25 and Phe25-Tyr26
-
-
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
show the reaction diagram
-
prevalent cleavage sites are Gly20-Glu21, Phe24-Phe25 and Phe25-Tyr26
15 different peptide fragments
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
show the reaction diagram
-
the others are Leu6-Cys(SO3-)7, Ala14-Leu15, Gly8-Ser9, His10-Leu11, Leu15-Tyr16, His5-Leu6 and Leu17-Val18
13 different peptide fragments
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
show the reaction diagram
-
10 cleavage sites
-
-
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
show the reaction diagram
-
10 cleavage sites
15 different peptide fragments
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
show the reaction diagram
-
7 major and 3 minor sites
-
-
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
show the reaction diagram
-
oxidized form
-
-
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
show the reaction diagram
-
oxidized form
15 different peptide fragments
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
show the reaction diagram
-
oxidized form
13 different peptide fragments
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
show the reaction diagram
Mus musculus male ICR
-
prevalent cleavage sites are Gly20-Glu21, Phe24-Phe25 and Phe25-Tyr26, 10 cleavage sites, oxidized form
15 different peptide fragments
-
Insulin B-chain + H2O
Hydrolyzed insulin B-chain
show the reaction diagram
Homo sapiens PPH
-
prevalent cleavage sites are Gly20-Glu21, Phe24-Phe25 and Phe25-Tyr26, 10 cleavage sites, 7 major and 3 minor sites, oxidized form
-
-
-
interleukin-1beta + H2O
?
show the reaction diagram
-
meprin beta activates interleukin 18
-
-
?
L-Leu 2-naphthylamide + H2O
?
show the reaction diagram
-
-
-
-
-
laminin + H2O
fragments of laminin
show the reaction diagram
-
-
-
-
Laminin + H2O
?
show the reaction diagram
-
-
-
?
Leu-Val-Tyr 4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
poor substrate, hydrolysis at 6.2% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
-
-
-
Luliberin + H2O
?
show the reaction diagram
-
i.e. luteinizing-hormone releasing hormone, preferred cleavage site: Trp3-Ser4, other sites are Ser4-Tyr5 and Tyr5-Gly6
-
-
-
luteinizing hormone releasing hormone LHRH + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
N-Benzoyl-L-tyrosyl-4-aminobenzoate + H2O
N-Benzoyl-L-tyrosine + 4-aminobenzoate
show the reaction diagram
-
-
-
-
-
N-Benzoyl-L-tyrosyl-4-aminobenzoate + H2O
N-Benzoyl-L-tyrosine + 4-aminobenzoate
show the reaction diagram
-
i.e. PABA-peptide, rat, human, arylamidolysis
-
-
-
N-Benzoyl-L-tyrosyl-4-aminobenzoate + H2O
N-Benzoyl-L-tyrosine + 4-aminobenzoate
show the reaction diagram
Homo sapiens, Homo sapiens PPH
-
very poor substrate, t1/2 of more than 16 h
-
-
neuropeptide Y + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
neurotensin + H2O
?
show the reaction diagram
-
i.e. pyro-Glu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu, mouse, rat, cleavage sites: Glu-Asn, Asn-Lys
-
-
-
neurotensin + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
nidogen-1 + H2O
?
show the reaction diagram
-
cleavage at D67-R68 and Q363-H364
-
-
?
orcokinin + H2O
?
show the reaction diagram
-
-
-
-
?
Oxytocin + H2O
Hydrolyzed oxytocin
show the reaction diagram
-
poor substrate
-
-
Parathyroid hormone + H2O
?
show the reaction diagram
Homo sapiens, Homo sapiens PPH
-
involved in PTH-degradation in human kidney
-
-
-
Parathyroid hormone + H2O
Hydrolyzed parathyroid hormone
show the reaction diagram
-
i.e. hPTH-(1-84), in vivo and in vitro
-
-
parathyroid hormone fragment 13-34 + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
pro-interleukin 1beta + H2O
interleukin 1beta + H2O
show the reaction diagram
Q64230
cleavage at the H115-D116 bond, which is one amino acid N-terminal to the caspase-1 cleavage site and five amino acids C-terminal to the meprin beta site. Both oligomeric meprin A and recombinant meprin alpha are capable of cleaving
the biological activity of the pro-interleukin-1beta cleaved product produced by meprin A, is 3fold higher to that of the interleukin-1beta product produced by meprin b or caspase-1
-
?
pro-KLK7 + H2O
KLK7 + ?
show the reaction diagram
-
meprin beta cleaves pro-KLK7 between Gly17 and Asp18
-
-
?
procollagen III + H2O
?
show the reaction diagram
-
meprin alpha can process procollagen III
-
-
?
protein GRP + H2O
?
show the reaction diagram
-
-
-
-
?
protein LHRH + H2O
?
show the reaction diagram
-
-
-
-
?
protein PTH12-34 + H2O
?
show the reaction diagram
-
-
-
-
?
sCCK8NH2 + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
Secretin + H2O
?
show the reaction diagram
-
-
-
-
?
Secretin + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
Substance P + H2O
Hydrolyzed substance P
show the reaction diagram
-
-
-
-
-
Substance P + H2O
Hydrolyzed substance P
show the reaction diagram
-
best substrate
-
-
Substance P + H2O
Hydrolyzed substance P
show the reaction diagram
-
rat
-
-
-
Substance P + H2O
Hydrolyzed substance P
show the reaction diagram
-
cleavage sites: Glu6-Phe7, Phe7-Phe8, Phe8-Gly9
-
-
-
Substance P + H2O
?
show the reaction diagram
-
-
-
-
?
Substance P + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
Succinyl-Ala-Ala-Ala 4-nitroanilide + H2O
?
show the reaction diagram
-
arylamidolysis
-
-
-
Succinyl-Ala-Ala-Pro-Phe 4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
poor substrate, hydrolysis at 9% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
-
-
-
Succinyl-Ala-Pro-Ala 4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
poor substrate, hydrolysis at 2.8% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
-
-
-
Succinyl-Gly-Pro 4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
poor substrate, hydrolysis at 10.7% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
-
-
-
Succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
Homo sapiens, Homo sapiens PPH
-
-
-
-
-
Succinyl-Leu-Tyr 4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
poor substrate, hydrolysis at 5.6% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
-
-
-
tissue growth factor-alpha + H2O
?
show the reaction diagram
-
meprin alpha can process tissue growth factor-alpha
-
-
?
Tyr 4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
poor substrate, hydrolysis at 3.3% the rate of succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide
-
-
-
Tyr-Leu-Val-Cys(SO3-)-Gly-Glu-Arg-Gly + H2O
?
show the reaction diagram
Mus musculus, Mus musculus male ICR
-
synthetic peptide derived from insulin B-chain
-
-
-
valosin + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
vascular endothelial growth factor-A + H2O
?
show the reaction diagram
B3DKP9, Q5RHM1
-
-
-
?
vascular endothelial growth factor-A + H2O
?
show the reaction diagram
-
cleavage of the vascular endothelial growth factor-A monomer by meprin alpha yields in two distinct fragments of 19600 Da, the N-terminal cleavage site in human vascular endothelial growth factor-A165 is between Ala30 and Glu31 due to recombinant human meprin alpha activity
-
-
?
Vasoactive intestinal peptide + H2O
?
show the reaction diagram
-
peptide of the gastrointestinal tract
-
?
vinculin + H2O
?
show the reaction diagram
-
substrate identified by 2D IEF/SDS-PAGE-based image analysis
-
-
?
[Met5]enkephalin-Arg6-Phe7 + H2O
?
show the reaction diagram
-
-
-
-
-
lysyl oxidase + H2O
?
show the reaction diagram
-
substrate identified by 2D IEF/SDS-PAGE-based image analysis
-
-
?
additional information
?
-
-
hydrolysis occurs on carboxy side of aromatic residues
-
-
-
additional information
?
-
-
hydrolysis occurs on carboxy side of aromatic residues
-
-
-
additional information
?
-
-
poor substrates are compounds with 3 or less amino acids
-
-
-
additional information
?
-
-
little or no activity towards benzoylarginine 2-naphthylamide, benzoylglycylarginine, benzyloxycarbonyl-Glu-Tyr, acetyl-Phe 2-naphthylester
-
-
-
additional information
?
-
-
no hydrolysis of Leu 4-nitroanilide, benzoyl-Arg-4-nitroanilide, succinyl-Ala 4-nitroanilide, Arg 4-methylcoumarinin 7-amide, benzoyl-Phe-Val-Arg 4-methylcoumarin 7-amide, Gly-Gly-Phe-Leu, Tyr-Gly-Gly-Phe-Leu, Tyr-Gly-Gly-Phe-Met, Leu-Arg-Arg-Ala-Ser-Leu-Gly, Ala-Phe-Pro-Leu-Gly-Phe, benzoyl-Phe-Val-Arg
-
-
-
additional information
?
-
-
dansyl-(D)-Ala-Gly-4-phenylalanylglycine, [Leu]-enkephalin, [Met]-enkephalin
-
-
-
additional information
?
-
-
insulin, [Arg8]-vasopressin, cytochrome c, ovalbumin, serum albumin
-
-
-
additional information
?
-
-
hydrolyzes peptides of at least 8 amino acids and prefers peptide bonds flanked by hydrophobic or neutral amino acid residues although hydrolysis is not limited to these bonds
-
-
-
additional information
?
-
-
orcokinin and gastrin 17 are no substrates
-
?
additional information
?
-
-
orcokinin, gastrin 17, peptide YY, kinetensin, [Lys8]-vasopressin, somatostatin, kassinin, oxytocin, and alpha-neurokinin are no substrates
-
?
additional information
?
-
-
cleaves growth factors, extracellular matrix proteins, and biological active peptides
-
?
additional information
?
-
-
no substrate: intact collagen I
-
-
-
additional information
?
-
-
2D IEF/SDS-PAGE-based image analysis procedure to analyse candidate substrates for meprin in a cell culture system-based approach and identification of meprin substrates with cleaved non-trypsin-generated N- and C-termini in peptide fragments upon LC-MS/MS analysis
-
-
-
additional information
?
-
-
meprin interacts with epithelial Na+ channel (ENaC)
-
-
-
additional information
?
-
Homo sapiens PPH
-
hydrolysis occurs on carboxy side of aromatic residues, dansyl-(D)-Ala-Gly-4-phenylalanylglycine, [Leu]-enkephalin, [Met]-enkephalin
-
-
-
additional information
?
-
Homo sapiens PPH
-
poor substrates are compounds with 3 or less amino acids
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
collagen type IV + H2O
?
show the reaction diagram
-
meprin alpha can degrade collagen type IV
-
-
?
Parathyroid hormone + H2O
?
show the reaction diagram
Homo sapiens, Homo sapiens PPH
-
involved in PTH-degradation in human kidney
-
-
-
procollagen III + H2O
?
show the reaction diagram
-
meprin alpha can process procollagen III
-
-
?
tissue growth factor-alpha + H2O
?
show the reaction diagram
-
meprin alpha can process tissue growth factor-alpha
-
-
?
interleukin-1beta + H2O
?
show the reaction diagram
-
meprin beta activates interleukin 18
-
-
?
additional information
?
-
-
cleaves growth factors, extracellular matrix proteins, and biological active peptides
-
?
additional information
?
-
-
meprin interacts with epithelial Na+ channel (ENaC)
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Calcium
-
3 mol calcium per mol subunit (atomic absorption spectroscopy); metalloendopeptidase; tightly bound, no addition of Ca2+ required
Calcium
-
Ca2+ inhibits above 1 mM; metalloendopeptidase
Zinc
-
1 mol zinc per mol subunit (atomic absorption spectroscopy); metalloendopeptidase; tightly bound, no addition of Zn2+ required
Zinc
-
metalloendopeptidase; zinc binding motif; Zn2+ inhibits above 1 mM
Zinc
-
metalloendopeptidase
Zinc
-
zinc binding motif
Zinc
-
metalloendopeptidase; zinc binding motif; Zn2+ reactivates inactive apoenzyme
Zinc
-
1 mol zinc per mol subunit (atomic absorption spectroscopy); metalloendopeptidase; zinc binding motif; Zn2+ reactivates inactive apoenzyme
Zinc
-
metalloendopeptidase; zinc binding motif; Zn2+ reactivates inactive apoenzyme
Zn2+
-
5 zinc ligands proposed to coordinate zinc at the active site
Zn2+
-
zinc-dependent endopeptidase
Zn2+
-
zinc metalloendopeptidase
Zn2+
-
zinc-metalloendopeptidase
Calcium
-
3 mol calcium per mol subunit (atomic absorption spectroscopy); Ca2+ reactivates inactive apoenzyme; metalloendopeptidase
additional information
-
considerable stimulation of azocasein hydrolysis at ionic strength values up to 0.15-0.2
additional information
-
Cu2+ does not reactivate inactive apoenzyme
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1,10-phenanthroline
-
at neutral and alkaline pH-values, reversible by dialysis
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
2-(N-Hydroxycarboxamido)-4-methylpentanoyl-L-alanyl-glycylamide
-
i.e. Zinkov inhibitor
2-mercaptoethanol
-
-
2-mercaptoethanol
-
-
2-mercaptoethanol
-
-
Acetyl-Arg-Pro-Gly-Tyr hydroxamate
-
kinetics
actinonin
-
i.e. 3-[[1-[[2-(hydroxymethyl)-1-pyrolidinyl]carbonyl]-2-methylpropyl]carbamoyl]octano hydroxamic acid, strong, kinetics
actinonin
-
in a mouse model of sepsis induced by cecal ligation puncture that results in elevated levels of serum interleukin 1beta, meprin inhibitor actinonin significantly reduces levels of serum interleukin 1beta
actinonin
-
pre-ischemic treatment with actinonin at 10 or 30 mg/kg, i.v. dose-ependently attenuates the ischemia/reperfusion-induced renal injury in male rats, but fails to improve the renal injury in female rats
Arg-Pro-Pro-Gly-(4-nitro)Phe-Glu-Pro-Phe-Arg
-
-
batimastat
-
-
Ca2+
-
above 1 mM, metalloproteinase, does not require additional Ca2+
chymostatin
-
-
chymostatin
-
-
cysteine
-
not cystine
cysteine
-
-
cysteine
-
-
cysteine
-
-
dithioerythritol
-
-
doxycycline
-
-
DTT
-
strong
DTT
-
strong
EDTA
-
at neutral and alkaline pH-values, reversible by dialysis
EDTA
-
restored by divalent metal ions, Zn2+ being more effective than Ca2+ or Mg2+
EDTA
-
-
EGTA
-
-
EGTA
-
-
galardin
-
-
GM6001
-
Ilomastat
GSH
-
not oxidized form
homophenylalanine hydroxamate
-
-
Hydroxamyl-succinyl-Pro-Phe-Arg
-
kinetics
N-isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid
-
-
Pro-Leu-Gly hydroxamate
-
-
Pro-Leu-Gly-hydroxamate
-
-
Ro 32-7315
-
-
TAPI-0
-
i.e. tumour necrosis factor alpha protease inhibitor-0
TAPI-2
-
i.e. tumour necrosis factor alpha protease inhibitor-2
TNF-a processing enzyme inhibitor
-
TAPI-2
-
TNF-alpha processing enzyme inhibitor
-
TAPI-2
-
tyrosine hydroxamate
-
-
verapamil
-
verapamil at 1 mg/kg, i.v. can efficiently prevent the ischemic acute kidney injury in female rats, as well as male rats
Zn2+
-
above 1 mM, metalloproteinase, does not require additional Zn2+
Zn2+
-
zinc endopeptidase
L-Pro-L-Leu-Gly-hydroxamate
-
-
additional information
-
diisopropyl phosphofluoridate, p-hydroxymercuribenzoate, phenylmercurisulfonate, antipain, cystine, oxidized glutathione; iodoacetate; leupeptin; no inhibition by phosphoramidon; PMSF, pepstatin
-
additional information
-
-
-
additional information
-
hippuryl-His-Leu, His-Leu, benzamidine; soybean trypsin inhibitor
-
additional information
-
amastatin, bestatin, puromycin, N-tosyl-L-Phe chloromethyl ketone, monoclonal antibody HBB 3/716/36; iodoacetate; leupeptin; no inhibition by phosphoramidon; PMSF, pepstatin
-
additional information
-
iodoacetate; L-trans-epoxysuccinyl-leucylamido-(4-guanidino)-butane (i.e. E-64); no inhibition by phosphoramidon; soybean trypsin inhibitor
-
additional information
-
inhibitors of elastase, aminopeptidase, serine, aspartic or cysteic proteases; no inhibition by phosphoramidon
-
additional information
-
leupeptin; L-trans-epoxysuccinyl-leucylamido-(4-guanidino)-butane (i.e. E-64); NEM, tissue inhibitor of metalloproteinases; no inhibition by phosphoramidon; PMSF, pepstatin; soybean trypsin inhibitor
-
additional information
-
3,4-dichloroisocoumarin; iodoacetate; no inhibition by phosphoramidon; PMSF, pepstatin; soybean trypsin inhibitor
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KLK4
-
activator of meprin beta
-
KLK5
-
activator of meprin alpha and beta
-
neutrophil elastase
-
activator of meprin alpha
-
plasmin
-
activator of meprin alpha
-
Trypsin
-
-
-
Trypsin
-
activated by limited trypsin digestion
-
Trypsin
-
-
-
Trypsin
-
activator of meprin alpha and beta
-
KLK8
-
activator of meprin beta
-
additional information
-
contrary to meprin B only very little activation by trypsin treatment
-
additional information
-
no activation by organomercurials or trypsin treatment
-
additional information
-
alpha- and beta-tryptase, urokinase plasminogen activator, KLK2, KLK6, KLK7, and KLK11 do not activate meprin alpha and beta
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.22
2-Aminobenzoyl-Arg-Gly-Pro-Phe-Ser-Pro-(4-nitro)Phe-Arg
-
-
0.183
2-Aminobenzoyl-Arg-Hyp-Gly-Phe-Ser-Pro-(4-nitro)Phe-Arg
-
-
1.38
2-Aminobenzoyl-Arg-Pro-Gly-Ala-Ser-Pro-(4-nitro)Phe-Arg
-
-
1.22
2-Aminobenzoyl-Arg-Pro-Gly-Glu-Ser-Pro-(4-nitro)Phe-Arg
-
-
2.46
2-Aminobenzoyl-Arg-Pro-Gly-Leu-Ser-Pro-(4-nitro)Phe-Arg
-
-
0.402
2-Aminobenzoyl-Arg-Pro-Gly-Lys-Ser-Pro-(4-nitro)Phe-Arg
-
-
0.296
2-Aminobenzoyl-Arg-Pro-Ile-Phe-Ser-Pro-(4-nitro)Phe-Arg
-
-
0.0223
alpha-MSH
-
meprin A hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.292
alpha-MSH
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.331
Arg-Pro-Pro-Gly-(4-nitro)Phe-Ala-Pro-Phe-Arg
-
-
0.174
Arg-Pro-Pro-Gly-(4-nitro)Phe-Arg-Pro-Phe-Arg
-
-
0.182
Arg-Pro-Pro-Gly-(4-nitro)Phe-Lys-Pro-Phe-Arg
-
-
0.226
Arg-Pro-Pro-Gly-(4-nitro)Phe-Phe-Pro-Phe-Arg
-
-
0.29
Arg-Pro-Pro-Gly-(4-nitro)Phe-Ser-Pro-Phe-Arg
-
-
0.0121
bradykinin
-
pH 7.5, 37C, mutant Y226F
0.0163
bradykinin
-
pH 7.5, 37C, wild-type
0.101
bradykinin
-
meprin A hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.125
bradykinin
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.224
bradykinin
-
pH 7.5, 37C
0.11
cholecystokinin 8-sulfate
-
pH 7.5, 37C, mutant Y199K
0.23
cholecystokinin 8-sulfate
-
pH 7.5, 37C, mutant F161R
0.29
cholecystokinin 8-sulfate
-
pH 7.5, 37C, mutant P228K
0.49
cholecystokinin 8-sulfate
-
pH 7.5, 37C
0.2
gastrin
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.44
gastrin 17
-
pH 7.5, 37C, mutant Y199K
0.11
GRP
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
-
0.116
GRP-(14-27)
-
pH 7.5, 37C
0.0565
LHRH
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
-
0.156
LHRH
-
meprin A hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 for between 8-30 min
-
0.0732
orcokinin
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
-
0.0296
protein GRP
-
meprin A hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
-
0.018
protein PTH12-34
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.0672
protein PTH12-34
-
meprin A hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.0339
secretin
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.111
secretin
-
meprin A hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.0306
Substance P
-
meprin A hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.0413
Substance P
-
hydrolysis in 20 mM Tris-HCl, 150 mM NaCl, pH 7.5 between 8-30 min
0.118
Substance P
-
pH 7.5, 37C
0.12
valosin
-
pH 7.5, 37C
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.1
2-Aminobenzoyl-Arg-Gly-Pro-Phe-Ser-Pro-(4-nitro)Phe-Arg
-
-
26.7
2-Aminobenzoyl-Arg-Hyp-Gly-Phe-Ser-Pro-(4-nitro)Phe-Arg
-
-
98.5
2-Aminobenzoyl-Arg-Pro-Gly-Ala-Ser-Pro-(4-nitro)Phe-Arg
-
-
4.9
2-Aminobenzoyl-Arg-Pro-Gly-Glu-Ser-Pro-(4-nitro)Phe-Arg
-
-
12
2-Aminobenzoyl-Arg-Pro-Gly-Leu-Ser-Pro-(4-nitro)Phe-Arg
-
-
2.4
2-Aminobenzoyl-Arg-Pro-Gly-Lys-Ser-Pro-(4-nitro)Phe-Arg
-
-
133
2-Aminobenzoyl-Arg-Pro-Ile-Phe-Ser-Pro-(4-nitro)Phe-Arg
-
-
16.5
alpha-MSH
-
-
45.4
alpha-MSH
-
-
51.5
Arg-Pro-Pro-Gly-(4-nitro)Phe-Ala-Pro-Phe-Arg
-
-
19.6
Arg-Pro-Pro-Gly-(4-nitro)Phe-Arg-Pro-Phe-Arg
-
-
5
Arg-Pro-Pro-Gly-(4-nitro)Phe-Lys-Pro-Phe-Arg
-
-
7.6
Arg-Pro-Pro-Gly-(4-nitro)Phe-Phe-Pro-Phe-Arg
-
-
40.9
Arg-Pro-Pro-Gly-(4-nitro)Phe-Ser-Pro-Phe-Arg
-
-
3.7
bradykinin
-
-
13.4
bradykinin
-
pH 7.5, 37C
16.6
bradykinin
-
-
22
bradykinin
-
pH 7.5, 37C
3.8
cholecystokinin 8-sulfate
-
pH 7.5, 37C, mutant P228K
8.6
cholecystokinin 8-sulfate
-
pH 7.5, 37C
13.4
cholecystokinin 8-sulfate
-
pH 7.5, 37C, mutant F161R
14.2
cholecystokinin 8-sulfate
-
pH 7.5, 37C, mutant Y199K
0.4
gastrin
-
-
10.8
gastrin 17
-
pH 7.5, 37C, mutant Y199K
17.4
Glucagon
-
pH 7.5, 37C
6.3
orcokinin
-
-
-
4.6
parathyphoid hormone 12-34
-
-
19.6
protein GRP
-
-
-
24.6
protein GRP
-
-
-
5.1
protein LHRH
-
-
-
39.4
protein LHRH
-
-
-
10.5
protein PTH12-34
-
-
4.4
secretin
-
-
8.4
secretin
-
-
11.8
secretin
-
pH 7.5, 37C
5.2
Substance P
-
-
12.1
Substance P
-
-
18.8
valosin
-
pH 7.5, 37C
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00002
actinonin
-
pH 7.5, 37C
0.0044
batimastat
-
pH 7.5, 37C
0.074
captopril
-
pH 7.5, 37C
0.00017
galardin
-
pH 7.5, 37C
0.00053
L-Pro-L-Leu-Gly-hydroxamate
-
pH 7.5, 37C
0.0004
N-isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid
-
pH 7.5, 37C
0.0016
Ro 32-7315
-
pH 7.5, 37C
0.0022
TAPI-0
-
pH 7.5, 37C
0.0015
TAPI-2
-
pH 7.5, 37C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.005
actinonin
-
-
0.18
actinonin
-
-
40
captopril
-
-
0.008
CGS 27023A
-
-
0.016
CGS 27023A
-
-
0.0033
CONA 65
-
-
2
CONA 65
-
-
0.04
CONA 68
-
-
-
0.05
CONA 68
-
-
-
0.17
CONA 71
-
-
-
0.25
CONA 71
-
-
-
0.065
CONA 73
-
-
-
0.31
CONA 73
-
-
-
12
doxycycline
-
-
20
doxycycline
-
-
0.06
GM6001
-
Ilomastat
0.6
GM6001
-
Ilomastat
0.1
homophenylalanine hydroxamate
-
-
0.8
homophenylalanine hydroxamate
-
-
0.4
Pro-Leu-Gly hydroxamate
-
-
16
Pro-Leu-Gly hydroxamate
-
-
0.08
TNF-alpha processing enzyme inhibitor
-
-
-
0.8
TNF-alpha processing enzyme inhibitor
-
-
-
0.1
tyrosine hydroxamate
-
-
1.1
tyrosine hydroxamate
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00363
-
succinyl-Ala-Ala-Ala 4-nitroanilide
0.095
-
Tyr-Leu-Val-Cys(SO3-)-Gly-Glu-Arg-Gly
0.9
-
mutant N152Q
1.38
-
oxidized insulin B-chain, trypsin-treated enzyme
1.4
-
mutant N426Q and N41Q
1.6
-
mutant N614Q
2
-
mutant N270Q
2.1
-
mutant N330Q
2.2
-
mutant N546Q
2.4
-
mutant N234Q
2.9
-
mutant Y226F
2.9
-
specific activity of homo-oligomeric meprin A against PTH
3.2
-
wild-type
3.3
-
mutant N553Q
4.2
-
specific activity of homo-oligomeric meprin A against PTH
4.54
-
n-bradykinin
5.9
-
mutant N452Q
20.8
-
wild-type
2700
-
specific activity of homo-oligomeric meprin A against gelatin
20500
-
specific activity of homo-oligomeric meprin A against azocasein
20800
-
specific activity of homo-oligomeric meprin A against azocasein
25000
-
specific activity of homo-oligomeric meprin A against gelatin
additional information
-
4.6673 mg azocasein/min/mg (untreated enzyme), 7.2512 mg azocasein/min/mg (trypsin-treated enzyme)
additional information
-
-
additional information
-
-
additional information
-
0.096 mg gelatin/min/mg
additional information
-
3.25-13 mg azocasein/min/mg
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 8
-
gelatin as substrate
7.4
-
assay at
7.5 - 8
-
-
9.5
-
azocasein as substrate
additional information
-
pI: 4.3
additional information
-
pI: multiple bonds in the range of 4-5, presumably due to glycosylation
additional information
-
marked microheterogeneity due to glycosylation with pIs in the range of 6-6.85
additional information
-
pI: multiple bonds in the range of 4-5, presumably due to glycosylation
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 9
-
rapid decrease of activity below 5 and above 9
7 - 8
-
plateau with maximal activity at pH 7.5-8
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
-
assay at
30
-
assay at; nitrobradykinin assay
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
in human epidermis, meprin alpha is expressed exclusively in the keratinocytes of the stratum basale, whereas meprin beta is restricted to the cells of the stratum granulosum
Manually annotated by BRENDA team
-
Madin-Darby canine kidney epithelial cells
Manually annotated by BRENDA team
-
from duodenum to rectum
Manually annotated by BRENDA team
-
higher specific activity in distal ileum than in proximal duodenum
Manually annotated by BRENDA team
-
intestinal epithelium
Manually annotated by BRENDA team
Homo sapiens PPH
-
higher specific activity in distal ileum than in proximal duodenum
-
Manually annotated by BRENDA team
-
lumen of proximal tubule, juxtamedullary nephrons
Manually annotated by BRENDA team
Q64230
kidney cortex
Manually annotated by BRENDA team
-
Madin-Darby canine kidney epithelial cells
Manually annotated by BRENDA team
-
in skin, meprins are located in separate layers of human epidermis
Manually annotated by BRENDA team
-
in human epidermis, meprin alpha is expressed exclusively in the keratinocytes of the stratum basale
Manually annotated by BRENDA team
-
in human epidermis, meprin beta is restricted to the cells of the stratum granulosum
Manually annotated by BRENDA team
Mus musculus male ICR, Homo sapiens PPH
-
-
-
Manually annotated by BRENDA team
additional information
-
tissue distribution (immuno-peroxidase staining), not in brain or spinal cord
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
membrane-bound
Manually annotated by BRENDA team
-
cell surface metalloproteinase, alphabeta-heterodimers firmly attached to brush border membrane, alpha2-homodimers only associated with membrane
Manually annotated by BRENDA team
-
intrinsic protein
Manually annotated by BRENDA team
-
beta subunits are type I integral membrane proteins and alpha subunits are disulfide linked to or non-covalently associated with membrane-anchored meprin beta subunits
Manually annotated by BRENDA team
-
renal brush border membrane
Manually annotated by BRENDA team
-
renal brush border membrane
Manually annotated by BRENDA team
-
apical membrane of intestinal epithelial cells
Manually annotated by BRENDA team
Mus musculus male ICR
-
renal brush border membrane
-
Manually annotated by BRENDA team
Homo sapiens PPH
-
apical membrane of intestinal epithelial cells
-
Manually annotated by BRENDA team
Homo sapiens PPH
-
-
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
74300
-
homooligomeric isoform, active, monomer, MALDI-TOF mass spectroscopy
652414
77700
-
homooligomeric isoform, latent, monomer, MALDI-TOF mass spectroscopy
652414
86000
-
monomeric molecular mass of a meprin alpha-subunit
685446
95000
-
SDS-PAGE
652026
140000 - 180000
-
rat, SDS-PAGE, non-reducing conditions
31029
148000
-
homooligomeric isoform, active, dimer, MALDI-TOF mass spectroscopy
652414
152000
-
heterooligomeric isoform, active, dimer, MALDI-TOF mass spectroscopy
652414
156000
-
homooligomeric isoform, latent, dimer, MALDI-TOF mass spectroscopy
652414
166000
-
heterooligomeric isoform, latent, dimer, MALDI-TOF mass spectroscopy
652414
167000
-
mouse, native enzyme, sedimentation equilibrium centrifugation with 4 M guanidine-HCl
31026
171000
-
mouse, SDS-PAGE, 3-20% gradient gel, non-reducing conditions
31026
200000
-
human, SDS-PAGE, non-reducing conditions
31021, 31027
204000
-
mouse, alpha2 homodimer, SDS-PAGE, non-reducing conditions
31026
220000
-
rat, SDS-PAGE, non-reducing conditions
31023
224000
-
mouse, alphabeta homodimer, SDS-PAGE, non-reducing conditions
31026
245000
-
mouse, PAGE in the presence of 4 M urea
31026
250000
-
above, mouse, SDS-PAGE, 10% homogenous gel, non-reducing conditions
31026
270000 - 320000
-
mouse, gel filtration
31018, 31031
320000
-
mouse, gel filtration, SDS-PAGE in the absence of 2-mercaptoethanol
31019, 31031
350000
-
rat, gel filtration
31029
360000
-
mouse, sedimentation equilibrium centrifugation
31026
495000
-
mouse, PAGE
31026
additional information
-
amino acid composition
31019
additional information
-
amino acid sequence alignment of meprin A and PPH
31022
additional information
-
amino acid composition (of meprin A and B)
31024
additional information
-
amino acid sequence of protease domain of meprin A compared to that of meprin B, EC 3.4.24.63
31028
additional information
-
-
31031
additional information
-
amino acid sequence, domain structure and tertiary structure deduced from cDNAs
31031
additional information
-
molecular weight above the highest marker 669000, gel filtration
652135
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
2 * 70000, human, SDS-PAGE after enzymatic deglycosylation
dimer
-
2 * 91000, human, SDS-PAGE, reducing conditions
dimer
-
2 * 100000, human, SDS-PAGE in the presence of DTT
octamer
-
8 * 90000, SDS-PAGE
oligomer
-
-
oligomer
-
x * 69000 + x * 79000, mouse, deglycosylated alpha and beta-subunit, SDS-PAGE in the presence of 2-mercaptoethanol
oligomer
-
x * 80000, rat, SDS-PAGE, reducing conditions
oligomer
-
x * 90000, mouse, SDS-PAGE, reducing conditions
oligomer
-
x * 86000, mouse, performic acid oxidized enzyme, sedimentation equilibrium centrifugation with 4 M guanidine-HCl
oligomer
-
x * 81000, mouse, SDS-PAGE in the presence of 2-mercaptoethanol
oligomer
-
heterooligomer
tetramer
-
SDS-PAGE
tetramer
-
SDS-PAGE
tetramer
-
x * 90000 + x * 110000, mouse, SDS-PAGE
tetramer
-
4 * 85000, mouse
tetramer
-
4 * 85000, mouse
tetramer
-
4 * 90000, mouse, SDS-PAGE, reducing conditions
tetramer
-
under reducing conditions
tetramer
-
disulfide-bridged dimers (alpha2 or alphabeta) aggregate non-covalently to form higher MW complexes, predominantly tetramers
tetramer
-
rat
tetramer
-
in the presence of 2-mercaptoethanol
tetramer
-
in the presence of 2-mercaptoethanol
tetramer
Mus musculus male ICR
-
4 * 90000, mouse, SDS-PAGE, reducing conditions
-
dimer
Homo sapiens PPH
-
2 * 100000, human, SDS-PAGE in the presence of DTT, 2 * 91000, human, SDS-PAGE, reducing conditions, 2 * 70000, human, SDS-PAGE after enzymatic deglycosylation
-
additional information
-
the mouse enzyme is composed of disulfide linked dimers associating non-covalently to form tetramers and sometimes higher order oligomers
additional information
-
the basic covalently linked structure is a dimer
additional information
-
two distinct subunit types
additional information
-
dimeric meprin seems to be catalytically active
additional information
-
beta-subunit is a type I transmembrane protein
additional information
-
enzyme forms oligomers of ten or more subunits with intersubunit disulfide bonds and further association of subunits. No single glycan is essential for oligomer formation
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
no sialic acid
glycoprotein
-
highly glycosylated
glycoprotein
Homo sapiens PPH
-
highly glycosylated, no sialic acid
-
glycoprotein
-
-
glycoprotein
-
complex-type glycosylation
glycoprotein
-
about 18% carbohydrates, mostly N-linked sugars
glycoprotein
-
30% Asp-linked carbohydrates, no glycolipid anchor
glycoprotein
-
no sialic acid
glycoprotein
-
30% oligosaccharides
glycoprotein
-
nine out of ten potential glycoslytation sites are glycosylated. Removal of two glycans at N234 and N270, as well as removal of glycan at N452, decrease the chemical and thermal stability of the homooligomer without affecting quarternary structure
glycoprotein
Mus musculus male ICR
-
complex-type glycosylation
-
glycoprotein
-
-
glycoprotein
-
30% Asp-linked carbohydrates, no glycolipid anchor
glycoprotein
-
no sialic acid
glycoprotein
-
30% oligosaccharides
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7
-
below, rapid irreversible denaturation
31019
7.5
-
t1/2: 30 min at 60C
31019
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
52
-
quite stable, less than 10% activity lost in 30 min
650461
55
-
wild-type enzyme retains 55% activity after 20 min, similar results for the mutants N41Q, N330Q, N426Q, N452Q, N546Q, and N553Q, mutants N234Q, N270Q, and N614Q retains 10% activity after 20 min, N152Q retains 6% activity after 5 min
652026
58
-
t1/2: 50 min
31024
60
-
t1/2: 30 min at pH 7.5
31019
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Solubilized PPH is rather labile, immobilization by protein A-Sepharose stabilizes
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, immobilized enzyme, 3 months
-
-20C, 1 mg enzyme/ml, more than a year with little loss of activity
-
4C, 1 mg enzyme/ml at least 2 weeks with little loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
from partially purified microvillar membranes; immunoaffinity chromatography; to near homogeneity
-
to near homogeneity
-
partial
-
purification of oligomeric meprin A from kidney cortex
-
recombinant enzyme
-
solubilized from 100000 g sediment with toluene and trypsin
-
immunoaffinity chromatography
-
purification of oligomeric meprin A from kidney cortex
Q64230
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed as a recombinant protein
-
human PPH
-
expressed in human embryonic kidney 293 cells
-
expressed in human embryonic kidney 293 cells ATCC 1573 CRL
-
human embryonic kidney 293 cells stably transfected with cDNA
-
human PPH
-
meprin alpha subunit
-
pcDNAI/Amp plasmid containing full-length wild-type meprin alpha-subunit cDNA transfected into MDCK cells and human embryonic kidney 293 cells
-
homooligomeric meprin A produced by transfecting cells with alpha or beta cDNA
-
meprin alpha subunit
Q64230
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
F161R
-
site-directed mutagenesis
N152Q
-
site-directed mutagenesis
N152Q/N270Q
-
no formation of intersubunit disulfide bonds and noncovalent association of subunits, loss of enzymatic activity
N234Q
-
site-directed mutagenesis
N270Q
-
site-directed mutagenesis
N330Q
-
site-directed mutagenesis
N41Q
-
site-directed mutagenesis
N426Q
-
site-directed mutagenesis
N452Q
-
site-directed mutagenesis
N546Q
-
site-directed mutagenesis
N553Q
-
site-directed mutagenesis
N614Q
-
site-directed mutagenesis
P228K
-
site-directed mutagenesis
Y199K
-
site-directed mutagenesis
Y226F
-
site-directed mutagenesis
H167A
-
site-directed mutagenesis
additional information
-
replacement of enzyme transmembrane and cytoplasmic domains, alphaT and alphaC, with their beta counterparts allows rapid movement of the alpha subunit to the cell surface. Enzyme alphaT and alphaC domains substituted into mephrin beta delayed movement of this chimera through the secretory pathway. Enzyme mutant C320ADELTAI, lacking a 56 amino acid inserted domain and unable to form disulfide bridges or higher order oligomers, is transported through the secretory pathway, but more slowly than mephrin beta
additional information
P28825
meprin A subunit alpha knock-out mice exhibit a more severe intestinal injury and inflammation than their wild-type counterparts following oral administration of dextran sulfate sodium
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
no significant differences in the overall excretion patterns among patients with diabetes mellitus compared with the nephrotic-range proteinuria group and control
medicine
-
genetic association of gene MEP1A encoding the alpha-subunit of meprin A with inflammatory bowel disease in patients with ulcerative colitis. Meprin-alpha mRNA is decreased in inflamed mucosa of patients with ulcerative colitis
medicine
-
meprin alpha is a therapeutic target in cardiovascular diseases or in tumor growth inhibition
medicine
-
db/db mice lacking the hypothalamic leptin receptor, representing a model of type 2 diabetes mellitus, manifest decreased enzyme and meprin-beta gene and protein expression before the development of overt kidney disease. Inverse relationship between renal enzyme content and the severity of the renal injury. Treatment with an inhibitor of angiotensin-converting enzyme is more effective than ANG II receptor type I blocker therapy in ameliorating diabetic nephrosis
medicine
P28825
meprin A subunit alpha knock-out mice exhibit a more severe intestinal injury and inflammation than their wild-type counterparts following oral administration of dextran sulfate sodium
medicine
-
meprin inhibition is therapeutically useful in atherosclerosis prevention
pharmacology
-
in a mouse model of sepsis induced by cecal ligation puncture that results in elevated levels of serum interleukin 1beta, meprin inhibitor actinonin significantly reduces levels of serum interleukin 1beta
medicine
-
animals treated with streptozocin, representing a model of type 1 diabetes mellitus, show inverse relationship between renal enzyme content and the severity of the renal injury
pharmacology
-
ischemic acute kidney injury was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. At 24 h after reperfusion, renal function and histology of both males and females showed significant deterioration. The degrees of renal dysfunction and histological damage are much more severe in males than in females. Pre-ischemic treatment with actinonin at 10 or 30 mg/kg i.v., dose-ependently attenuats the ischemia/reperfusion-induced renal injury in male rats, but fails to improve the renal injury in female rats. Verapamil at 1 mg/kg i.v., can efficiently prevent the ischemic acute kidney injury in female rats, as well as male rats