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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-06-13 22:20:22 UTC
HMDB IDHMDB01035
Secondary Accession NumbersNone
Metabolite Identification
Common NameAngiotensin II
DescriptionAngiotensin II is a hormone that may act on the central nervous system to regulate renal sympathetic nerve activity, renal function, and, therefore, blood pressure. Angiotensin II is produced locally within the kidney and mediates tissue injury through a series of nonhemodynamic effects. angiotensin II is not only involved in the regulation of blood pressure, water and sodium homeostasis, and control of other neurohumoral systems, but also leads to excessive production of reactive oxygen species and to hypertrophy, proliferation, migration, and apoptosis of vascular cells. Angiotensin II is one of the main factors involved in hypertension-induced tissue damage. This peptide regulates the inflammatory process. Angiotensin II activates circulating cells, and participates in their adhesion to the activated endothelium and subsequent transmigration through the synthesis of adhesion molecules, chemokines and cytokines. Among the intracellular signals involved in angiotensin II-induced inflammation, the production of reactive oxygen species and the activation of nuclear factor-kappaB are the best known. Classical, well-defined actions of Angiotensin II in the brain include the regulation of hormone formation and release, the control of the central and peripheral sympathoadrenal systems, and the regulation of water and sodium intake. As a consequence of changes in the hormone, sympathetic and electrolyte systems, feedback mechanisms in turn modulate the activity of the brain Angiotensin II systems. There are two Angiotensin II systems in the brain. The discovery of brain Angiotensin II receptors located in neurons inside the blood brain barrier confirmed the existence of an endogenous brain Angiotensin II system, responding to Angiotensin II generated in and/or transported into the brain. In addition, Angiotensin II receptors in circumventricular organs and in cerebrovascular endothelial cells respond to circulating Angiotensin II of peripheral origin. Thus, the brain responds to both circulating and tissue Angiotensin II, and the two systems are integrated. (PMID: 17147923 , 16672146 , 16601568 , 16481883 , 16075377 ).
Structure
Thumb
Synonyms
  1. 1-8-Angiotensin I
  2. 1-L-Aspasaginyl-5-L-valyl angiotensin octapeptide
  3. Ang II
  4. Angiotensin 2
  5. Angiotensin II (human)
  6. Angiotensin II (mouse)
  7. Angiotonin
  8. Asp-arg-val-TYR-ile-his-pro-phe
  9. Human angiotensin II
  10. Hypertensin
  11. Ile(5)-angiotensin II
Chemical FormulaC50H71N13O12
Average Molecular Weight1046.1786
Monoisotopic Molecular Weight1045.534514801
IUPAC Name(3S)-3-amino-3-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S,2S)-1-{[(2S)-1-[(2S)-2-{[(1S)-1-carboxy-2-phenylethyl]carbamoyl}pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]carbamoyl}-2-methylbutyl]carbamoyl}-2-(4-hydroxyphenyl)ethyl]carbamoyl}-2-methylpropyl]carbamoyl}-4-[(diaminomethylidene)amino]butyl]carbamoyl}propanoic acid
Traditional Name(3S)-3-amino-3-{[(1S)-1-{[(1S)-1-{[(1S)-1-{[(1S,2S)-1-{[(2S)-1-[(2S)-2-{[(1S)-1-carboxy-2-phenylethyl]carbamoyl}pyrrolidin-1-yl]-3-(3H-imidazol-4-yl)-1-oxopropan-2-yl]carbamoyl}-2-methylbutyl]carbamoyl}-2-(4-hydroxyphenyl)ethyl]carbamoyl}-2-methylpropyl]c
CAS Registry Number11128-99-7
SMILES
CC[C@H](C)[C@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O
InChI Identifier
InChI=1S/C50H71N13O12/c1-5-28(4)41(47(72)59-36(23-31-25-54-26-56-31)48(73)63-20-10-14-38(63)45(70)60-37(49(74)75)22-29-11-7-6-8-12-29)62-44(69)35(21-30-15-17-32(64)18-16-30)58-46(71)40(27(2)3)61-43(68)34(13-9-19-55-50(52)53)57-42(67)33(51)24-39(65)66/h6-8,11-12,15-18,25-28,33-38,40-41,64H,5,9-10,13-14,19-24,51H2,1-4H3,(H,54,56)(H,57,67)(H,58,71)(H,59,72)(H,60,70)(H,61,68)(H,62,69)(H,65,66)(H,74,75)(H4,52,53,55)/t28-,33-,34-,35-,36-,37-,38-,40-,41-/m0/s1
InChI KeyCZGUSIXMZVURDU-JZXHSEFVSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAmino Acids, Peptides, and Analogues
ClassPeptides
Sub ClassN/A
Other Descriptors
  • Angiotensin [KO:K09821](KEGG)
  • Aromatic Heteropolycyclic Compounds
  • amino acid zwitterion(ChEBI)
Substituents
  • 1,3 Aminoalcohol
  • Alpha Amino Acid Or Derivative
  • Aminoimidazole
  • Amphetamine Or Derivative
  • Carboxamide Group
  • Carboxylic Acid
  • Dicarboxylic Acid Derivative
  • Guanidine
  • Imidazole
  • Imidazolyl Carboxylic Acid Derivative
  • N Acyl Alpha Amino Acid
  • N Substituted Alpha Amino Acid
  • Phenol
  • Phenol Derivative
  • Polyamine
  • Primary Aliphatic Amine (Alkylamine)
  • Pyrrolidine
  • Secondary Carboxylic Acid Amide
  • Tertiary Carboxylic Acid Amide
Direct ParentPeptides
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locationsNot Available
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.016ALOGPS
logP-0.87ALOGPS
logP-5.3ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)3.15ChemAxon
pKa (Strongest Basic)10.83ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count17ChemAxon
Hydrogen Donor Count13ChemAxon
Polar Surface Area408.84 Å2ChemAxon
Rotatable Bond Count29ChemAxon
Refractivity269.81 m3·mol-1ChemAxon
Polarizability107.02 Å3ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular LocationsNot Available
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot Available
Normal
  • Not Applicable
details
Cerebrospinal Fluid (CSF)Detected and Quantified6.418e-06 +/- 2.535e-06 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified6.418e-06 +/- 2.535e-06 uMAdult (>18 years old)Femalenormal details
UrineDetected and Quantified0.0000012 +/- 0.0000002 umol/mmol creatinineAdult (>18 years old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.0000574 +/- 0.0000030 uMAdult (>18 years old)BothHypertension details
Cerebrospinal Fluid (CSF)Detected and Quantified1.922e-06 +/- 1.741e-06 uMAdult (>18 years old)Not Specifiedneuromyelitis optica spectrum disorders with anti-Anti-aquaporin-4(AQP4) antibody details
Cerebrospinal Fluid (CSF)Detected and Quantified3.625e-06 +/- 1.473e-06 uMAdult (>18 years old)Not Specifiedmultiple sclerosis details
Cerebrospinal Fluid (CSF)Detected and Quantified4.907e-06 +/- 2.171e-06 uMAdult (>18 years old)Not Specifiedinflammatory neuropathies details
Cerebrospinal Fluid (CSF)Detected and Quantified1.922e-06 +/- 1.741e-06 uMAdult (>18 years old)FemaleNeuromyelitis optica details
Cerebrospinal Fluid (CSF)Detected and Quantified5.174e-06 +/- 2.238e-06 uMAdult (>18 years old)Both
Neurological diseases
details
Cerebrospinal Fluid (CSF)Detected and Quantified3.0000e-06 +/- 1.597e-06 uMAdult (>18 years old)Bothmultiple sclerosis details
Associated Disorders and Diseases
Disease References
Hypertension
  1. Sim MK, Qui XS: Angiotensins in plasma of hypertensive rats and human. Regul Pept. 2003 Mar 28;111(1-3):179-82. Pubmed: 12609766
Associated OMIM IDs
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022383
KNApSAcK IDNot Available
Chemspider ID150504
KEGG Compound IDC02135
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkAngiotensin II
NuGOwiki LinkHMDB01035
Metagene LinkHMDB01035
METLIN IDNot Available
PubChem Compound172198
PDB IDNot Available
ChEBI ID2719
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Malpas SC, Ramchandra R, Guild SJ, McBryde F, Barrett CJ: Renal sympathetic nerve activity in the development of hypertension. Curr Hypertens Rep. 2006 Jun;8(3):242-8. Pubmed: 17147923
  2. Durvasula RV, Shankland SJ: The renin-angiotensin system in glomerular podocytes: mediator of glomerulosclerosis and link to hypertensive nephropathy. Curr Hypertens Rep. 2006 May;8(2):132-8. Pubmed: 16672146
  3. Wassmann S, Nickenig G: Pathophysiological regulation of the AT1-receptor and implications for vascular disease. J Hypertens Suppl. 2006 Mar;24(1):S15-21. Pubmed: 16601568
  4. Ruiz-Ortega M, Esteban V, Ruperez M, Sanchez-Lopez E, Rodriguez-Vita J, Carvajal G, Egido J: Renal and vascular hypertension-induced inflammation: role of angiotensin II. Curr Opin Nephrol Hypertens. 2006 Mar;15(2):159-66. Pubmed: 16481883
  5. Saavedra JM: Brain angiotensin II: new developments, unanswered questions and therapeutic opportunities. Cell Mol Neurobiol. 2005 Jun;25(3-4):485-512. Pubmed: 16075377

Enzymes

General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH (By similarity).
Gene Name:
PGD
Uniprot ID:
P52209
Molecular weight:
53139.56
General function:
Involved in ribose-5-phosphate isomerase activity
Specific function:
Not Available
Gene Name:
RPIA
Uniprot ID:
P49247
Molecular weight:
33268.72
General function:
Involved in metallopeptidase activity
Specific function:
Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety
Gene Name:
ACE
Uniprot ID:
P12821
Molecular weight:
149713.7
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system
Gene Name:
AGTR1
Uniprot ID:
P30556
Molecular weight:
41060.5
General function:
Involved in catalytic activity
Specific function:
Catalyzes the reversible epimerization of D-ribulose 5-phosphate to D-xylulose 5-phosphate.
Gene Name:
RPE
Uniprot ID:
Q96AT9
Molecular weight:
19537.385
General function:
Involved in oxidoreductase activity
Specific function:
Not Available
Gene Name:
PGD
Uniprot ID:
A9Z1X1
Molecular weight:
32311.5
General function:
Involved in metallopeptidase activity
Specific function:
Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.
Gene Name:
ACE2
Uniprot ID:
Q9BYF1
Molecular weight:
92462.4
Reactions
Angiotensin II + Water → angiotensin-(1-7) + L-Phenylalaninedetails
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Receptor for angiotensin II. Cooperates with MTUS1 to inhibit ERK2 activation and cell proliferation
Gene Name:
AGTR2
Uniprot ID:
P50052
Molecular weight:
41183.4
General function:
Involved in protein binding
Specific function:
Appears to be a negative regulator of type-1 angiotensin II receptor-mediated signaling by regulating receptor internalisation as well as mechanism of receptor desensitization such as phosphorylation. Induces also a decrease in cell proliferation and angiotensin II-stimulated transcriptional activity
Gene Name:
AGTRAP
Uniprot ID:
Q6RW13
Molecular weight:
17419.0