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Record Information
Version3.6
Creation Date2006-03-08 15:00:54 UTC
Update Date2016-02-11 01:05:04 UTC
HMDB IDHMDB01897
Secondary Accession NumbersNone
Metabolite Identification
Common NameSubstance P
DescriptionSubstance P (SP), is an 11-amino acid neuropeptide. SP is a member of the tachykinin family of peptides because it induces rapid smooth muscle contraction in guinea pig ileum and rat duodenum. Other members of the tachykinin family, sharing common carboxyl terminal Phe-X-Gly-Leu-met-NH2 sequences in mammals, include neurokinin A and neurokinin B. In mammals, tachykinins are produced by two genes, preprotachykinin-A (PPT-A) and preprotachykinin-B (PPT-B), and SP is a product of the PPT-A gene. SP is localized in the central nervous system as well as in several peripheral tissues, including the entire length of the gastrointestinal tract as well as the colon. The main sources of SP in the gut include the myenteric and submucosal plexus, intrinsic sensory neurons, as well as sensory neurons originating from the dorsal root ganglia. A newly identified gene, preprotachykinin C gene, encodes for the sequence of a new preprotachykinin protein designated hemokinin (HK) and produced primarily by hematopoietic cells. HK binds with high selectivity to NK-1R and has similar in vivo potency to SP. Like SP, HK is an 11-amino acid peptide having ~55% amino acid similarity to SP. The effects of SP are mediated by three different G-protein-coupled receptors (GPCRs), namely neurokinin (NK)-1, 2, and 3. SP binds with high affinity to NK-1 receptor (NK-1R), and with low affinity to NK-2 and 3 receptors. NK-1 receptors are present in both small intestine and colon of animals and humans and are localized in a variety of cells, including nerves, smooth muscle, immune cells, glands, endothelial cells, as well as epithelial cells. Although NK-1 receptors have been associated with several intestinal pathophysiologic conditions (see below), NK-2 receptors have been linked mostly with circular muscle contraction, and are localized in circular muscle and muscularis mucosae. Although NK-2 receptors are present predominantly on smooth muscle and, like NK-1, can affect gut motility, NK-3 receptors are expressed predominantly in neurons and can stimulate or diminish muscle contraction indirectly following SP binding to neuronal cells in the submucosal and myenteric nerve plexuses of the gastrointestinal tract. NK-3 receptors also provide slow excitatory synaptic input to neurons in ganglia of the sphincter of Oddi. Thus, both NK-2 and NK-3 receptors affect motility responses in the GI, but there is very little evidence that they are involved in neuroimmune interactions. (PMID: 17192554 ).
Structure
Thumb
Synonyms
ValueSource
Arg-pro-lys-pro-GLN-GLN-phe-phe-gly-leu-met-NH2HMDB
Chemical FormulaC63H98N18O13S
Average Molecular Weight1347.63
Monoisotopic Molecular Weight1346.728146002
IUPAC Name(2S)-2-[(2R)-2-{[(2S)-1-[(2S)-6-amino-2-{[(2R)-1-[(2S)-2-amino-5-carbamimidamidopentanoyl]pyrrolidin-2-yl]formamido}hexanoyl]pyrrolidin-2-yl]formamido}-4-carbamoylbutanamido]-N-[(1R)-1-{[(1R)-1-[({[(1R)-1-{[(1S)-1-carbamoyl-3-(methylsulfanyl)propyl]carbamoyl}-3-methylbutyl]carbamoyl}methyl)carbamoyl]-2-phenylethyl]carbamoyl}-2-phenylethyl]pentanediamide
Traditional Name(2S)-2-[(2R)-2-{[(2S)-1-[(2S)-6-amino-2-{[(2R)-1-[(2S)-2-amino-5-carbamimidamidopentanoyl]pyrrolidin-2-yl]formamido}hexanoyl]pyrrolidin-2-yl]formamido}-4-carbamoylbutanamido]-N-[(1R)-1-{[(1R)-1-[({[(1R)-1-{[(1S)-1-carbamoyl-3-(methylsulfanyl)propyl]carbamoyl}-3-methylbutyl]carbamoyl}methyl)carbamoyl]-2-phenylethyl]carbamoyl}-2-phenylethyl]pentanediamide
CAS Registry Number33507-63-0
SMILES
CSCC[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)CNC(=O)[C@@H](CC1=CC=CC=C1)NC(=O)[C@@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCNC(N)=N)C(N)=O
InChI Identifier
InChI=1S/C63H98N18O13S/c1-37(2)33-45(57(89)74-41(53(68)85)27-32-95-3)73-52(84)36-72-54(86)46(34-38-15-6-4-7-16-38)78-58(90)47(35-39-17-8-5-9-18-39)79-56(88)42(23-25-50(66)82)75-55(87)43(24-26-51(67)83)76-59(91)49-22-14-31-81(49)62(94)44(20-10-11-28-64)77-60(92)48-21-13-30-80(48)61(93)40(65)19-12-29-71-63(69)70/h4-9,15-18,37,40-49H,10-14,19-36,64-65H2,1-3H3,(H2,66,82)(H2,67,83)(H2,68,85)(H,72,86)(H,73,84)(H,74,89)(H,75,87)(H,76,91)(H,77,92)(H,78,90)(H,79,88)(H4,69,70,71)/t40-,41-,42-,43+,44-,45+,46+,47+,48+,49-/m0/s1
InChI KeyInChIKey=ADNPLDHMAVUMIW-SGTHPBLKSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues.
KingdomOrganic compounds
Super ClassOrganic Polymers
ClassPolypeptides
Sub ClassNot Available
Direct ParentPolypeptides
Alternative Parents
Substituents
  • Polypeptide
  • Alpha peptide
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid amide
  • Phenylpropylamine
  • Amphetamine or derivatives
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Pyrrolidine-2-carboxamide
  • Pyrrolidine carboxylic acid or derivatives
  • N-acylpyrrolidine
  • Fatty acyl
  • Benzenoid
  • N-acyl-amine
  • Fatty amide
  • Monocyclic benzene moiety
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Primary carboxylic acid amide
  • Guanidine
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Dialkylthioether
  • Sulfenyl compound
  • Carboximidamide
  • Thioether
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary amine
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Imine
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
BiofunctionNot Available
ApplicationNot Available
Cellular locationsNot Available
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point148 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.023 mg/mLALOGPS
logP-0.15ALOGPS
logP-5.8ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)11.49ChemAxon
pKa (Strongest Basic)11.9ChemAxon
Physiological Charge3ChemAxon
Hydrogen Acceptor Count18ChemAxon
Hydrogen Donor Count16ChemAxon
Polar Surface Area516.63 Å2ChemAxon
Rotatable Bond Count42ChemAxon
Refractivity362.14 m3·mol-1ChemAxon
Polarizability141.28 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular LocationsNot Available
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified3.6e-6 +/- 1.8e-6 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.323-1.07 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified7e-06 +/- 6e-07 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified1.41e-4 +/- 1.42e-05 uMNewborn (0-30 days old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.022673 +/- 0.00834 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0227 +/- 0.0083 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified5e-05 +/- 2.3e-06 uMChildren (1-13 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified9.5e-06 +/- 1.5e-06 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified9.6e-06 +/- 3.2e-06 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified1.44e-05 +/- 4.2e-06 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified7.425e-07 +/- 7.425e-08 uMNot SpecifiedNot Specified
Normal
details
Cerebrospinal Fluid (CSF)Detected and Quantified8.910e-07 +/- 5.940e-07 uMNot SpecifiedNot Specified
Normal
details
Cerebrospinal Fluid (CSF)Detected and Quantified1.23e-05 +/- 2.8e-06 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified2.339e-05 +/- 1.188e-06 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified2.354e-05 +/- 1.559e-06 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified2.309e-05 +/- 1.782e-06 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified4.39e-05 +/- 9.9e-06 uMAdult (>18 years old)Not SpecifiedNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified4.9e-6 +/- 2.7e-6 uMAdult (>18 years old)Both
Migraine
details
Cerebrospinal Fluid (CSF)Detected and Quantified1.37-16.3 uMNot SpecifiedNot SpecifiedCobalamin deficiency details
Cerebrospinal Fluid (CSF)Detected and Quantified8.64e-4 +/- 3.576e-4 uMNewborn (0-30 days old)Not SpecifiedSpina Bifida details
Cerebrospinal Fluid (CSF)Detected and Quantified0.15 uMNot SpecifiedNot SpecifiedSpina Bifida details
Cerebrospinal Fluid (CSF)Detected and Quantified2.5e-4 +/- 2.82e-05 uMNewborn (0-30 days old)Not SpecifiedPremature details
Cerebrospinal Fluid (CSF)Detected and Quantified1.41e-4 +/- 1.42e-05 uMNewborn (0-30 days old)Not SpecifiedFull term newborn details
Cerebrospinal Fluid (CSF)Detected and Quantified3.61e-05 +/- 2.7e-06 uMNot SpecifiedNot SpecifiedFibromyalgia details
Cerebrospinal Fluid (CSF)Detected and Quantified4.01e-05 +/- 2.7e-06 uMAdult (>18 years old)Not SpecifiedFibromyalgia details
Cerebrospinal Fluid (CSF)Detected and Quantified2.92e-05 +/- 5e-06 uMNot SpecifiedNot SpecifiedFibromyalgia details
Cerebrospinal Fluid (CSF)Detected and Quantified3.51e-05 +/- 3.2e-06 uMNot SpecifiedNot SpecifiedFibromyalgia details
Cerebrospinal Fluid (CSF)Detected and Quantified1.92e-05 +/- 6.7e-06 uMNot SpecifiedNot SpecifiedSleep Apnea Syndrome details
Cerebrospinal Fluid (CSF)Detected and Quantified9.653e-07 +/- 8.910e-07 uMNot SpecifiedNot Specified
Chronic headache
details
Cerebrospinal Fluid (CSF)Detected and Quantified5.198e-07 +/- 3.713e-07 uMNot SpecifiedNot Specified
Chronic headache
details
Cerebrospinal Fluid (CSF)Detected and Quantified1.99e-05 +/- 3.9e-06 uMAdult (>18 years old)Not SpecifiedTerm Pregnancy details
Cerebrospinal Fluid (CSF)Detected and Quantified2.176e-05 +/- 1.188e-06 uMAdult (>18 years old)Not SpecifiedAlzheimer's disease details
Cerebrospinal Fluid (CSF)Detected and Quantified3.111e-05 +/- 2.822e-06 uMAdult (>18 years old)Not SpecifiedAlzheimer's disease details
Cerebrospinal Fluid (CSF)Detected and Quantified2.658e-05 +/- 2.153e-06 uMAdult (>18 years old)Not SpecifiedNon-Alzheimer dementias details
Cerebrospinal Fluid (CSF)Detected and Quantified2.562e-05 +/- 9.653e-07 uMAdult (>18 years old)Not Specified
Neurological disorders without cognitive impairment
details
Cerebrospinal Fluid (CSF)Detected and Quantified2.770e-05 +/- 2.0000e-06 uMAdult (>18 years old)Not SpecifiedAlzheimer's Disease details
Cerebrospinal Fluid (CSF)Detected and Quantified3.03e-05 +/- 7.8e-06 uMAdult (>18 years old)Not SpecifiedNarcolepsy details
UrineDetected and Quantified9.8e-6 +/- 3.6e-6 umol/mmol creatinineAdult (>18 years old)FemaleMalignant solid neoplasm details
UrineDetected and Quantified1.1e-5 (5e-7 - 3.6e-5) umol/mmol creatinineAdult (>18 years old)BothCisplatin containing chemotherapy details
Associated Disorders and Diseases
Disease References
Migraine
  1. Fusayasu E, Kowa H, Takeshima T, Nakaso K, Nakashima K: Increased plasma substance P and CGRP levels, and high ACE activity in migraineurs during headache-free periods. Pain. 2007 Apr;128(3):209-14. Epub 2006 Nov 22. [17123735 ]
Associated OMIM IDs
DrugBank IDDB05875
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB002259
KNApSAcK IDNot Available
Chemspider ID23215821
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkSubstance P
NuGOwiki LinkHMDB01897
Metagene LinkHMDB01897
METLIN IDNot Available
PubChem Compound44359816
PDB IDNot Available
ChEBI ID332416
References
Synthesis ReferenceEgorova, S. V.; Akhrem, A. A. Synthesis of substance P. Vestsi Akademii Navuk BSSR, Seryya Khimichnykh Navuk (1989), (1), 46-51.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Koon HW, Pothoulakis C: Immunomodulatory properties of substance P: the gastrointestinal system as a model. Ann N Y Acad Sci. 2006 Nov;1088:23-40. [17192554 ]
  2. Rothstein RD, Johnson E, Ouyang A: Substance P: mechanism of action and receptor distribution at the feline ileocecal sphincter region. Am J Physiol. 1989 Sep;257(3 Pt 1):G447-53. [2476938 ]
  3. Grimsholm O, Rantapaa-Dahlqvist S, Dalen T, Forsgren S: Observations favouring the occurrence of local production and marked effects of bombesin/gastrin-releasing peptide in the synovial tissue of the human knee joint--comparisons with substance P and the NK-1 receptor. Neuropeptides. 2008 Apr;42(2):133-45. doi: 10.1016/j.npep.2007.12.008. [18289674 ]
  4. Sequence Information [Link]

Enzymes

General function:
Involved in carboxylesterase activity
Specific function:
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name:
BCHE
Uniprot ID:
P06276
Molecular weight:
68417.575
References
  1. Lockridge O: Substance P hydrolysis by human serum cholinesterase. J Neurochem. 1982 Jul;39(1):106-10. [6177830 ]
General function:
Involved in peroxidase activity
Specific function:
Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular weight:
68995.625
References
  1. Koon HW, Zhao D, Zhan Y, Rhee SH, Moyer MP, Pothoulakis C: Substance P stimulates cyclooxygenase-2 and prostaglandin E2 expression through JAK-STAT activation in human colonic epithelial cells. J Immunol. 2006 Apr 15;176(8):5050-9. [16585602 ]
  2. Sio SW, Ang SF, Lu J, Moochhala S, Bhatia M: Substance P upregulates cyclooxygenase-2 and prostaglandin E metabolite by activating ERK1/2 and NF-kappaB in a mouse model of burn-induced remote acute lung injury. J Immunol. 2010 Nov 15;185(10):6265-76. Epub 2010 Oct 6. [20926798 ]
  3. Gallicchio M, Rosa AC, Benetti E, Collino M, Dianzani C, Fantozzi R: Substance P-induced cyclooxygenase-2 expression in human umbilical vein endothelial cells. Br J Pharmacol. 2006 Mar;147(6):681-9. [16432508 ]
General function:
Involved in monooxygenase activity
Specific function:
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name:
CYP19A1
Uniprot ID:
P11511
Molecular weight:
57882.48
References
  1. Gobbetti A, Zerani M, Di Fiore MM, Botte V: Relationships among GnRH, substance P, prostaglandins, sex steroids and aromatase activity in the brain of the male lizard Podarcis sicula sicula during reproduction. J Reprod Fertil. 1994 Aug;101(3):523-9. [7525952 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is:substance P > substance K > neuromedin-K
Gene Name:
TACR1
Uniprot ID:
P25103
Molecular weight:
46250.5