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Information on EC 3.4.15.1 - peptidyl-dipeptidase A and Organism(s) Rattus norvegicus and UniProt Accession P47820
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3.4.15.1 peptidyl-dipeptidase ASpecify your search results
Word Map
- 3.4.15.1
- hypertension
-
blocker
- cardiovascular
- arterial
-
antihypertensive
- cardiac
-
renin-angiotensin
- ventricular
- myocardial
- captopril
-
systolic
-
diuretic
- coronary
- renin
-
aceis
- infarction
-
beta-blockers
- enalapril
- glomerular
-
diastolic
-
ejection
- proteinuria
- mellitus
-
placebo
- hypertrophy
- aldosterone
- nephropathy
- creatinine
-
hemodynamic
- bradykinin
-
congestive
- ras
-
vasodilator
-
normotensive
- statin
-
renin-angiotensin-aldosterone
- hg
- sarcoidosis
- losartan
- aspirin
-
prescript
-
double-blind
- angiotensinogen
-
renoprotective
-
pressor
- digoxin
-
all-cause
-
renovascular
-
microalbuminuria
-
hypotensive
- drug development
- veterinary medicine
- medicine
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
release of a C-terminal dipeptide, oligopeptide-/-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of angiotensin I to angiotensin II, with increase in vasoconstrictor activity, but no action on angiotensin II
Synonyms
angiotensin-converting enzyme, angiotensin converting enzyme, angiotensin converting enzyme inhibitor, angiotensin i-converting enzyme, angiotensin-converting-enzyme, angiotensin i converting enzyme, ace-1, kininase ii, angiotensin-i converting enzyme, angiotensin-converting enzyme-2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ACE
angiotensin 1 converting enzyme
-
-
-
-
angiotensin converting enzyme
angiotensin I-converting enzyme
angiotensin-converting enzyme
carboxycathepsin
-
-
-
-
carboxypeptidase, dipeptidyl
-
-
-
-
CD143 antigen
-
-
-
-
DCP
Dipeptidyl carboxypeptidase
-
-
-
-
dipeptidyl carboxypeptidase I
-
-
-
-
endothelial cell peptidyl dipeptidase
-
-
-
-
kininase II
-
-
-
-
PDH
-
-
-
-
peptidase P
-
-
-
-
peptidyl dipeptidase
-
-
-
-
peptidyl dipeptidase A
-
-
-
-
peptidyl dipeptidase I
-
-
-
-
peptidyl dipeptidase-4
-
-
-
-
peptidyl dipeptide hydrolase
-
-
-
-
peptidyl-dipeptide hydrolase
-
-
-
-
peptidyldipeptide hydrolase
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-
-
-
ACE
-
-
-
-
ACE
-
-
angiotensin converting enzyme
-
-
-
-
angiotensin I-converting enzyme
-
-
-
-
angiotensin-converting enzyme
-
-
-
-
DCP
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9015-82-1
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
angiotensin I + H2O
angiotensin II + L-His-L-Leu
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
-
i.e. substance P, lung and brain ACE cleave substance P via two pathways. In one pathway ACE first releases Gly-Leu-Met-NH2 and then dipeptides sequentially from the carboxyl terminus. The other first produces Leu-Met-NH2 and then releases dipeptides to leave substance P(1-5)
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly + Leu-Met-NH2
bradykinin + H2O
L-Phe-L-Arg + L-Ser-L-Pro + L-Arg-L-Pro-L-Pro-Gly-L-Phe
-
-
-
-
?
hippuryl-His-Leu + H2O
hippuric acid + His-Leu
-
-
81211, 81219, 81220, 81241, 81244, 81252, 81254, 81283, 667885, 680293, 681562, 707783, 710160, 731569, 732968
-
-
?
hippuryl-L-His-L-Leu + H2O
hippuric acid + L-His-L-Leu
-
-
-
-
?
His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 + H2O
His-Lys-Thr-Asp-Ser-Phe-Val-Gly + Leu-Met-NH2
-
i.e. substance K, degraded by striatal but not by lung enzyme
-
-
?
Luteinizing hormone-releasing hormone + H2O
?
-
degraded by striatal and by lung enzyme
-
-
?
LVVYPWTQRY + H2O
LVVYPWTQ + RY + LVVY + PW + LVVYPW + TQ
-
-
dipeptide TQ is unidentified. Sequential removal of dipeptides in three consecutive steps
?
physalaemin + H2O
pGlu-Ala-Asp-Pro-Asn-Lys-Phe-Tyr-Gly + Leu-Met-NH2
-
degraded by striatal and by lung enzyme
-
-
?
angiotensin I + H2O
angiotensin II + His-Leu
-
i.e. DRVYIHPFHL
i.e. DRVYIHPF
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly + Leu-Met-NH2
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly + Leu-Met-NH2
-
i.e. substance P
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly + Leu-Met-NH2
-
lung and brain ACE cleave substance P via two pathways. In one pathway ACE first releases Gly-Leu-Met-NH2 and then dipeptides sequentially from the carboxyl terminus. The other first produces Leu-Met-NH2 and then releases dipeptides to leave substance P(1-5)
-
?
bradykinin + H2O
?
-
bradykinin is a nonapeptide released from high molecular weight kininogen, it exerts its vasodilatory effect mainly by stimulation of B2 receptors
-
-
?
additional information
?
-
-
potential role of follicular enzyme in early stages of follicular maturation and atresia
-
-
?
additional information
?
-
-
ACE degrades bradykinin, other vasoactive peptides, and activates angiotensin
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
angiotensin I + H2O
angiotensin II + His-Leu
-
i.e. DRVYIHPFHL
i.e. DRVYIHPF
-
?
angiotensin I + H2O
angiotensin II + L-His-L-Leu
-
-
-
-
?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 + H2O
?
-
i.e. substance P, lung and brain ACE cleave substance P via two pathways. In one pathway ACE first releases Gly-Leu-Met-NH2 and then dipeptides sequentially from the carboxyl terminus. The other first produces Leu-Met-NH2 and then releases dipeptides to leave substance P(1-5)
-
-
?
bradykinin + H2O
L-Phe-L-Arg + L-Ser-L-Pro + L-Arg-L-Pro-L-Pro-Gly-L-Phe
-
-
-
-
?
bradykinin + H2O
?
-
bradykinin is a nonapeptide released from high molecular weight kininogen, it exerts its vasodilatory effect mainly by stimulation of B2 receptors
-
-
?
additional information
?
-
-
potential role of follicular enzyme in early stages of follicular maturation and atresia
-
-
?
additional information
?
-
-
ACE degrades bradykinin, other vasoactive peptides, and activates angiotensin
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
NaCl
Zinc
-
0.3 mM ZnCl2 completely reverses the inhibition caused by 0.1 mM EDTA
NaCl
-
stimulates hydrolysis of hippuryl-His-Leu in concentration-dependent manner between 0 and 300 mM
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5-(3,4,5-trihydroxyphenyl)-gamma-valerolactone
the metabolite has a hypotensive effect in vivo
5-(3,5-dihydroxyphenyl)-gamma-valerolactone
the metabolite has a hypotensive effect in vivo
SPB1
Bacillus subtilis crude lipopeptide biosurfactant, the biosurfactant displays a potent inhibition of ACE activity in vitro, IC50 is 1.37 mg/ml
-
15B2
-
an inhibitor isolated from the culture broth of Actinomadura sp. No. 937ZE-1
chitooligosaccharide derivatives
-
i.e. COS, chitosan derivatives, polycationic polymers comprised principally of glucosamine units, generated via either chemical or enzymatic hydrolysis of chitosan. ACE inhibitory activity of hetero-COS, derived from crab chitin, is dependent on the degree of deacetylation of chitosan
-
D-mannitol
-
antihypertensive effect in spontaneously hypertensive rats by oral administration
dexamethasone
-
markedly inhibits the plasma extravasion in the tracheal mucosa produced by substance P. The simultanous inhibition of neutral endopeptidase and angiotensin converting enzyme completely reverses the effect of dexamethasone on substance P-induced extravasion
enalaprilat
-
inhibits ACE and the bradykinin degradation in vivo, which is reversed by insulin
ESIINF
-
the inhibitor produces an acute blood-pressure-lowering effect in spontaneously hypertensive rats upon a single oral administration
Gly-L-Ala-Hyp-Gly-L-Pro-L-Ala-Gly-L-Pro-Gly-Gly-L-Ile-Hyp-Gly-L-Glu-L-Arg-Gly
-
-
Gly-Phe-Hyp-Gly-Thr-Hyp-Gly-Leu-Hyp-Gly-Phe
-
inhibitory peptide derived from chicken breast muscle possesses hypotensive activity for spontaneously hypertensive rats
inhibitory peptides from rice dreg hydrolysate
-
significant antihypertensive action and no other side effects by oral administration in spontaneous hypertension rats
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KRQKYDI
-
competitive inhibitor, the strongest inhibitor among reported troponin-originated peptides. The inhibhitor is slowly hydrolyzed by treatment with angiotensin I-converting enzyme. When KRQKYDI is administered orally to spontaneously hypertensive rats at a dose of 10 mg/kg, a temporary antihypertensive activity is observed at 3 and 6 h after administration
L-681,176
-
purification of the inhibitor found in the culture filtrate of Streptomyces sp. MA 5143
NaCl
-
concentration dependent inhibition of hippuryl-His-Leu between 0 and 100 mM
phlorotannins
-
e.g. from Ahnfeltiopsis flabelliformis, Ecklonia cava, Ecklonia stolonifera, Pelvetia siliqousa, and Undaria pinnatifida, phenolic compounds formed by the polymerization of phloroglucinol or defined as 1,3,5-trihydroxybenzene monomer units and biosynthesized through the acetate-malonate pathway. They are highly hydrophilic components with a wide range of molecular sizes ranging between 126-650 kDa. A closed ring dibenzo-1,4-dioxin moiety may be crucial for ACE inhibitory effects
-
quercetin 3-O-alpha-(6''-p-coumaroylglucosyl-beta -1,2-rhamnoside)
-
IC50: 0.351 mM
quercetin-3-O-alpha-(6''-caffeoylglucosyl-beta-1,2-rhamnoside)
-
IC50: 0.1589 mM
sardine peptide
-
a protein hydrolysate derived from muscles of sardines, inhibits in vivo and reduces the blood glucose level, but not the plasma insulin level
-
trandolapril
-
the angiotensin-converting enzyme inhibitor has no significant effect on apoptosis induced via endotoxic shock with Escherichia coli lipopolysaccharides
Trp-Pro-Glu-Ala-Ala-Glu-Leu-Met-Met-Glu-Val-Asp-Pro
-
noncompetitive inhibitor.The peptide has an antihypertensive effect according to the time-course measurement after oral administration to spontaneously hypertensive rats. Maximal reduction is detected 3 h after oral administration at a dose of 10 mg/kg of body weight
Val-Lys-Lys-Val-Leu-Gly-Asn-Pro
-
the angiotensin-I converting enzyme inhibitory peptide derived from porcine skeletal muscle myosin is a noncompetitive inhibitor that is slowly hydrolyzed by angiotensin-I converting enzyme. At the dose of 10 mg/kg, this peptide shows antihypertensive activity after a maximum of 3 h of administration
YRGGLEPINF
-
the inhibitor produces an acute blood-pressure-lowering effect in spontaneously hypertensive rats upon a single oral administration
captopril
-
-
captopril
-
lipophilic ACE inhibitors quinapril, enalapril, and captopril increase the survival and lifetime of rats with experimental chronic heart failure
captopril
-
the anngiotensin converting enzyme inhibitor captopril modifies conditioned place preference induced by morphine and morphine withdrawal signs in rats
captopril
-
ACE inhibition during pregnancy and lactation in adult offspring rats induces behavioural changes, e.g. in the open field test, overview
captopril
-
inhibits in vivo and reduces the blood glucose level, but not the plasma insulin level
enalapril
-
acute angiotensin-converting enzyme inhibition evokes bradykinin-induced sympathetic activation in diabetic rats
enalapril
-
lipophilic ACE inhibitors quinapril, enalapril, and captopril increase the survival and lifetime of rats with experimental chronic heart failure
enalapril
-
reduces the liver tissue transforming growth factor beta-1 and has an ameliorating effect on the fibrosis markers transforming growth factor beta-1 and matrix metalloproteinase-2. Enalapril does not affect the process of liver fibrosis at all (induced in rats by bile-duct ligation)
enalapril
-
the angiotensin-converting enzyme inhibitor has no significant effect on apoptosis induced via endotoxic shock with Escherichia coli lipopolysaccharides
genistein
-
0.003-0.3 mM genistein decreases the angiotensin-converting enzyme activity in blood plasma in a concentration-dependent manner
genistein
-
the isoflavone inhibits ACE in plasma and alters the vascular responses to angiotensin I and bradykinin, overview
lisinopril
-
angiotensin-converting enzyme inhibitor enhances the liver regeneration in rats after partial hepatectomy. Angiotensin-converting enzyme enhanced the hepatic regenerative response to PH by two independent mechanisms: an activation of B2 receptors and inhibition of angiotensin II production, both of which may stimulate production of hepatocyte growth factor, resulting in enhancement of the hepatic regeneration
lisinopril
-
therapeutic resistance to angiotensin converting enzyme inhibition is related to a difference in the combination of renal pharmacodynamic and pharmacokinetic characteristics in non-responders, primarily consisting of increased renal expression of angiotensin converting enzyme and higher angiotensin converting enzyme inhibitor clearance
lisinopril
-
treatment with 75 mg/l lisinopril significantly reduces renal ACE activity without affecting renal ACE2 activity
N-[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl-L-proline
-
accelerated nitrotyrosine content in the renal cortex during high-glucose conditions is prevented by treatment with the angiotensin-converting enzyme inhibitor treatment. The suppressed degradation of nitrotyrosine in the renal cortex by the angiotensin-converting enzyme inhibitor enhances both superoxide anion degradation per se and antioxidative effects including activation of superoxide dismutase
N-[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl-L-proline
-
independent of diet enalapril treatment decreases food intake, energetic gain and body weight in normotensive young rats, followed by reduced body fat mass and serum leptin
nicotianamine
-
mixed inhibition. The preferential inhibition of circulating and tissue angiotensin I-converting enzyme by nicotianamine can contribute to the suppression of hypertension
perindopril
-
chronic administration of perindopril results in a decrease in body adiposity
perindopril
-
chronic in vivo administration of the angiotensin-converting enzyme inhibitor reduces apoptosis induced via endotoxic shock with Escherichia coli lipopolysaccharides
perindopril
-
in growing spontaneously hypertensive rats, chronic treatment with perindopril enhances untrained exercise capacity, while it does no affect acquired exercise capacity as a result of exercise training. Perindopril promotes adaptive changes of skeletal muscle in response to exercise such as increases in capillary density and percentage of type I fibre
perindopril
-
decreases food intake and circulating insulin in both diet groups, and hepatic ACE activity in high fat fed animals only, while decreased plasma leptin concentration with ACE inhibition is only evident in chow fed animals
quinapril
-
lipophilic ACE inhibitors quinapril, enalapril, and captopril increase the survival and lifetime of rats with experimental chronic heart failure
quinapril
-
the angiotensin-converting enzyme inhibitor has no significant effect on apoptosis induced via endotoxic shock with Escherichia coli lipopolysaccharides
quinapril
-
18 mg/kg quinapril per day feeding for 3 days significantly reduces blood plasma ACE activity by 80%, quinapril administration for 16 days greatly decreases blood plasma ACE activity by 88% with 18 mg/kg per day, ACE activities in the heart, lung, and skeletal muscles of the 16-day ACE-inhibition with 18 mg/kg per day are 9%, 16%, and 22% of the controls, respectively
ramipril
-
in the early phase of diabetes, the angiotensin-converting enzyme inhibitor reverses glomerular overexpression and activation of some critical growth factor pathways and increases protection against oxidative stress. These effects involve B2-kinin receptor activation
ramipril
-
the angiotensin-converting enzyme inhibitor has no significant effect on apoptosis induced via endotoxic shock with Escherichia coli lipopolysaccharides
additional information
effects of metabolites produced from (-)-epigallocatechin gallate by rat intestinal bacteria on angiotensin I-converting enzyme activity and blood pressure in spontaneously hypertensive rats. All of the metabolites show ACE inhibitory activities and the order of IC50 is hydroxyphenyl valeric acids > 5-(3,4,5-trihydroxyphenyl)-gamma-valerolactone > 5-(3,4,5-trihydroxyphenyl) 4-hydroxyvaleric acid >> 5-(3,5-dihydroxyphenyl) 4-hydroxyvaleric acid >> 5-(3,5-dihydroxyphenyl)-gamma-valerolactone. Among the catechins, galloylated catechins exhibit stronger ACE inhibitory activity than nongalloylated catechins. Measurement of systolic blood pressure (SBP) after oral administration
-
additional information
-
endogenous inhibitor from rat heart may modulate the activity of the enzyme in the heart in response to alterations of the oxidation-reduction balance in the tissue, MW of the inhibitor is about 100000 Da
-
additional information
-
design and properties of N-carboxyalkyldipeptide inhibitors
-
additional information
-
the presence of verticione, verticine, peimisine may be responsible, at least in part, for the antihypertensive action of the bulbs of Fritillaria ussuriensis
-
additional information
-
hot water extract of Tamogi-take mushroom, antihypertensive effect in spontaneously hypertensive rats by oral administration
-
additional information
-
isolation of angiotensin converting enzyme (ACE) inhibitory flavonoids from Sedum sarmentosum
-
additional information
-
angiotensin I-converting enzyme inhibitory peptides from protein hydrolysates by a soybean protease D3
-
additional information
-
tissue angiotensin converting enzyme inhibitors exert more pronounced antithrombotic effect than plasma ACE-Is in experimental thrombosis
-
additional information
-
chicken collagen hydrolysates possess ACE-inhibitory activities, chicken collagen hydrolysates inhibit about 30% of the activity of ACE, whereas further enzymatic treatment doubles their activities
-
additional information
-
not inhibited by MLN4760, SCH39370, amastatin bestatin, chymostatin, and p-chloromercuribenzoate
-
additional information
-
2.7fold peptide-enriched soy sauce-like seasoning, termed Fermented Soybean Seasoning, FSS, shows ACE inhibitory activity with an IC50 of 0.454 mg/ml, fermentation method, overview. FSS shows antihypertensive effects, overview
-
additional information
-
ACE inhibitory peptides derived from marine organisms show a strong suppressive effect on systolic blood pressure of spontaneously hypertensive rats, and this antihypertensive activity is similar with captopril, a commercial antihypertensive drug. Hydrophobicity of the N-terminus is one of the common features of ACE inhibitory peptides, and may contribute to the inhibitory activity. No side effect observed on rats after administration of antihypertensive peptides. The peptides exhibit antihypertensive activity in vivo rather than in vitro. An antihypertensive peptide isolated from bonito fish hydrolysate product, is hydrolyzed by ACE to produce a smaller peptide than the initial one, which has 8fold increased ACE inhibitory activity compared with the initial peptide. Polyphenolic compounds inhibit ACE activity through sequestration of the enzyme metal factor, Zn2+ ion
-
additional information
-
metabolic effects of low dose angiotensin converting enzyme inhibitor in dietary obesity in the rat
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Cl-
-
activation, optimal NaCl concentration for the brain enzyme in hydrolysis of LVVYPWTQRY is 10 mM, optimal concentration for hydrolysis of angiotensin I is 200 mM
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE