Kyotorphin (BioDeep_00000005058)

 

Secondary id: BioDeep_00000033516, BioDeep_00001868710

human metabolite Endogenous


代谢物信息卡片


(2S)-2-[(2S)-2-amino-3-(4-hydroxyphenyl)propanamido]-5-carbamimidamidopentanoic acid

化学式: C15H23N5O4 (337.175)
中文名称: TYR-ARG
谱图信息: 最多检出来源 Homo sapiens(feces) 36.01%

分子结构信息

SMILES: C(C[C@@H](C(=O)O)NC(=O)[C@H](Cc1ccc(cc1)O)N)CNC(=N)N
InChI: InChI=1S/C15H23N5O4/c16-11(8-9-3-5-10(21)6-4-9)13(22)20-12(14(23)24)2-1-7-19-15(17)18/h3-6,11-12,21H,1-2,7-8,16H2,(H,20,22)(H,23,24)(H4,17,18,19)

描述信息

Kyotorphin (L-tyrosyl-L-arginine) is a neuroactive dipeptide which plays a role in pain regulation in the brain. It was first isolated from bovine brain by Japanese scientists in 1979. Kyotorphin was named for the site of its discovery, Kyoto, Japan and because of its morphine- (or endorphin-) like analgesic activity. Kyotorphin has an analgesic effect, but it does not interact with the opioid receptors. Instead, it acts by releasing an Met-enkephalin and stabilizing it from degradation. It may also possess properties of neuromediator/neuromodulator. It has been shown that kyotorphin is present in the human cerebrospinal fluid and that it is lower in patients with persistent pain. [HMDB]
Kyotorphin (L-tyrosyl-L-arginine) is a neuroactive dipeptide which plays a role in pain regulation in the brain. It was first isolated from bovine brain by Japanese scientists in 1979. Kyotorphin was named for the site of its discovery, Kyoto, Japan and because of its morphine- (or endorphin-) like analgesic activity. Kyotorphin has an analgesic effect, but it does not interact with the opioid receptors. Instead, it acts by releasing an Met-enkephalin and stabilizing it from degradation. It may also possess properties of neuromediator/neuromodulator. It has been shown that kyotorphin is present in the human cerebrospinal fluid and that it is lower in patients with persistent pain.
D018373 - Peripheral Nervous System Agents > D018689 - Sensory System Agents
D002491 - Central Nervous System Agents > D000700 - Analgesics
D018377 - Neurotransmitter Agents > D018847 - Opioid Peptides
D018377 - Neurotransmitter Agents > D004723 - Endorphins
Kyotorphin is an endogenou neuroactive dipeptide with analgesic properties. Kyotorphin possesses anti-inflammatory and antimicrobial activity. Kyotorphin levels in cerebro-spinal fluid correlate negatively with the progression of neurodegeneration in Alzheimer's Disease patients[1].

同义名列表

16 个代谢物同义名

(2S)-2-[(2S)-2-amino-3-(4-hydroxyphenyl)propanamido]-5-carbamimidamidopentanoic acid; Kyotorphin, 14C-labeled, (L-tyr-L-arg)-isomer; Kyotorphin, 3H-labeled, (L-tyr-D-arg)-isomer; Kyotorphin, 3H-labeled, (L-tyr-L-arg)-isomer; Kyotorphin, (L-tyr-D-arg)-isomer; N(2)-L-Tyrosyl-L-arginine; Kyotorphin acetate salt; (D-Arg(2))-kyotorphin; L-Tyrosyl-L-arginine; L-Tyrosyl-D-arginine; tyrosylarginine; D-Kyotorphin; Kyotorphin; Kiotorphin; Tyr-arg; Kyotorphin



数据库引用编号

18 个数据库交叉引用编号

分类词条

相关代谢途径

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代谢反应

0 个相关的代谢反应过程信息。

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1 个相关的物种来源信息

在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有：

  • PubMed: 来源于PubMed文献库中的文献信息，我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表，这个列表按照代谢物同时出现的文献数量降序排序，取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
  • NCBI Taxonomy: 通过文献数据挖掘，得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序，取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
  • Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
  • Chemical Reaction: 在化学反应过程中，存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。

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亚细胞结构定位 关联基因列表
Cytoplasm 8 ACE, ARG2, CA1, CA3, CAST, MME, POMC, YARS1
Nucleus 2 PLCZ1, YARS1
cytosol 5 CA1, CA3, CAST, PLCZ1, YARS1
dendrite 4 MME, OPRM1, PDYN, PENK
nuclear body 1 YARS1
trans-Golgi network 1 MME
nucleoplasm 2 CAST, PLCZ1
Cell membrane 6 ACE, GPRC5A, MME, OPRD1, OPRM1, SLC15A2
Cell projection, axon 1 OPRM1
Multi-pass membrane protein 4 GPRC5A, OPRD1, OPRM1, SLC15A2
Synapse 4 MME, OPRM1, PDYN, TAC1
cell surface 1 MME
Golgi apparatus 1 OPRM1
Golgi membrane 1 INS
neuronal cell body 4 MME, PDYN, PENK, TAC1
presynaptic membrane 1 OPRD1
synaptic vesicle 1 MME
Cytoplasmic vesicle, secretory vesicle 1 NTS
Lysosome 1 ACE
Presynapse 1 MME
endosome 2 ACE, OPRM1
plasma membrane 9 ACE, GPRC5A, KNG1, MME, OPRD1, OPRM1, PDYN, PENK, SLC15A2
synaptic vesicle membrane 1 OPRD1
Membrane 6 ACE, CAST, MME, OPRD1, OPRM1, SLC15A2
apical plasma membrane 1 SLC15A2
axon 3 MME, OPRM1, TAC1
brush border 1 MME
extracellular exosome 6 ACE, CA1, GPRC5A, KNG1, MME, SLC15A2
endoplasmic reticulum 2 CAST, OPRM1
extracellular space 6 ACE, INS, KNG1, POMC, TAC1, YARS1
perinuclear region of cytoplasm 1 PLCZ1
mitochondrion 2 ARG2, CAST
intracellular membrane-bounded organelle 2 GPRC5A, NTS
pronucleus 1 PLCZ1
Single-pass type I membrane protein 1 ACE
Secreted 7 ACE, INS, NTS, PDYN, PENK, POMC, TRH
extracellular region 9 ACE, INS, KNG1, NTS, PDYN, PENK, POMC, TAC1, TRH
hippocampal mossy fiber to CA3 synapse 1 PDYN
mitochondrial matrix 1 ARG2
external side of plasma membrane 1 ACE
neuronal dense core vesicle lumen 1 PENK
perikaryon 2 OPRM1, PENK
cytoplasmic vesicle 1 MME
nucleolus 3 CAST, GPRC5A, PLCZ1
Early endosome 1 MME
Single-pass type II membrane protein 1 MME
vesicle 1 GPRC5A
Apical cell membrane 1 SLC15A2
Cytoplasm, perinuclear region 1 PLCZ1
Membrane raft 1 MME
focal adhesion 1 MME
collagen-containing extracellular matrix 1 KNG1
secretory granule 2 POMC, TRH
receptor complex 1 GPRC5A
neuron projection 2 OPRD1, OPRM1
Cytoplasmic vesicle, phagosome membrane 1 SLC15A2
phagocytic vesicle membrane 1 SLC15A2
Chromosome 1 CAST
Secreted, extracellular space 1 KNG1
brush border membrane 1 ACE
Nucleus, nucleolus 1 CAST
blood microparticle 1 KNG1
sperm midpiece 1 ACE
fibrillar center 1 CAST
endosome lumen 1 INS
Cytoplasmic vesicle membrane 1 GPRC5A
cell body fiber 1 PENK
Cell projection, dendrite 1 OPRM1
basal plasma membrane 1 ACE
secretory granule lumen 2 INS, POMC
secretory granule membrane 1 MME
Golgi lumen 1 INS
endoplasmic reticulum lumen 3 INS, KNG1, PENK
platelet alpha granule lumen 1 KNG1
axon terminus 4 NTS, OPRD1, PDYN, PENK
transport vesicle 2 INS, NTS
Endoplasmic reticulum-Golgi intermediate compartment membrane 1 INS
postsynaptic density membrane 1 OPRD1
neuronal dense core vesicle 2 OPRD1, PDYN
RNA polymerase I complex 1 CAST
RNA polymerase I transcription regulator complex 1 CAST
dendrite membrane 1 OPRD1
Cytoplasmic vesicle, secretory vesicle, chromaffin granule lumen 1 PENK
chromaffin granule lumen 1 PENK
symmetric synapse 1 PENK
synaptic vesicle lumen 1 PENK
sperm head 1 PLCZ1
neuron projection terminus 1 MME
[Angiotensin-converting enzyme, soluble form]: Secreted 1 ACE
[Isoform Testis-specific]: Cell membrane 1 ACE
[Isoform 12]: Cytoplasm 1 OPRM1
spine apparatus 1 OPRD1


文献列表

  • Tiago N Figueira, João M Freire, Catarina Cunha-Santos, Montserrat Heras, João Gonçalves, Anne Moscona, Matteo Porotto, Ana Salomé Veiga, Miguel A R B Castanho. Quantitative analysis of molecular partition towards lipid membranes using surface plasmon resonance. Scientific reports. 2017 03; 7(?):45647. doi: 10.1038/srep45647. [PMID: 28358389]
  • Katia Conceição, Pedro R Magalhães, Sara R R Campos, Marco M Domingues, Vasanthakumar G Ramu, Matthias Michalek, Philippe Bertani, António M Baptista, Montserrat Heras, Eduard R Bardaji, Burkhard Bechinger, Mônica Lopes Ferreira, Miguel A R B Castanho. The anti-inflammatory action of the analgesic kyotorphin neuropeptide derivatives: insights of a lipid-mediated mechanism. Amino acids. 2016 Jan; 48(1):307-18. doi: 10.1007/s00726-015-2088-9. [PMID: 26347373]
  • Pedro R Magalhães, Miguel Machuqueiro, António M Baptista. Constant-pH Molecular Dynamics Study of Kyotorphin in an Explicit Bilayer. Biophysical journal. 2015 May; 108(9):2282-90. doi: 10.1016/j.bpj.2015.03.052. [PMID: 25954885]
  • Isa D Serrano, Vasanthakumar G Ramu, Antónia R T Pinto, João M Freire, Isaura Tavares, Montserrat Heras, Eduard R Bardaji, Miguel A R B Castanho. Correlation between membrane translocation and analgesic efficacy in kyotorphin derivatives. Biopolymers. 2015 Jan; 104(1):1-10. doi: 10.1002/bip.22580. [PMID: 25363470]
  • Marta M B Ribeiro, Henri G Franquelim, Inês M Torcato, Vasanthakumar G Ramu, Montserrat Heras, Eduard R Bardaji, Miguel A R B Castanho. Antimicrobial properties of analgesic kyotorphin peptides unraveled through atomic force microscopy. Biochemical and biophysical research communications. 2012 Apr; 420(3):676-9. doi: 10.1016/j.bbrc.2012.03.065. [PMID: 22450328]
  • Joakim E Swedberg, Jonathan M Harris. Plasmin substrate binding site cooperativity guides the design of potent peptide aldehyde inhibitors. Biochemistry. 2011 Oct; 50(39):8454-62. doi: 10.1021/bi201203y. [PMID: 21877690]
  • Marta M B Ribeiro, Antónia R T Pinto, Marco M Domingues, Isa Serrano, Montserrat Heras, Eduard R Bardaji, Isaura Tavares, Miguel A Castanho. Chemical conjugation of the neuropeptide kyotorphin and ibuprofen enhances brain targeting and analgesia. Molecular pharmaceutics. 2011 Oct; 8(5):1929-40. doi: 10.1021/mp2003016. [PMID: 21830793]
  • Gyöngyi Horváth, László Mécs. Antinociception by endogenous ligands at peripheral level. Ideggyogyaszati szemle. 2011 Mar; 64(5-6):193-207. doi: ". [PMID: 21688721]
  • Miguel Machuqueiro, Sara R R Campos, Cláudio M Soares, António M Baptista. Membrane-induced conformational changes of kyotorphin revealed by molecular dynamics simulations. The journal of physical chemistry. B. 2010 Sep; 114(35):11659-67. doi: 10.1021/jp104418g. [PMID: 20707376]
  • Ying Huang, Xiuyan Jiang, Wei Wang, Jianping Duan, Guonan Chen. Separation and determination of l-tyrosine and its metabolites by capillary zone electrophoresis with a wall-jet amperometric detection. Talanta. 2006 Dec; 70(5):1157-63. doi: 10.1016/j.talanta.2006.03.009. [PMID: 18970894]
  • Sílvia C D N Lopes, Alexandre Fedorov, Miguel A R B Castanho. Chiral recognition of D-kyotorphin by lipidic membranes: relevance toward improved analgesic efficiency. ChemMedChem. 2006 Jul; 1(7):723-8. doi: 10.1002/cmdc.200600096. [PMID: 16902926]
  • Sílvia C D N Lopes, Cláudio M Soares, António M Baptista, Erik Goormaghtigh, Benedito J Costa Cabral, Miguel A R B Castanho. Conformational and orientational guidance of the analgesic dipeptide kyotorphin induced by lipidic membranes: putative correlation toward receptor docking. The journal of physical chemistry. B. 2006 Feb; 110(7):3385-94. doi: 10.1021/jp053651w. [PMID: 16494353]
  • Silvina A Bravo, Carsten Uhd Nielsen, Sven Frokjaer, Birger Brodin. Characterization of rPEPT2-mediated Gly-Sar transport parameters in the rat kidney proximal tubule cell line SKPT-0193 cl.2 cultured in basic growth media. Molecular pharmaceutics. 2005 Mar; 2(2):98-108. doi: 10.1021/mp049892q. [PMID: 15804184]
  • G Baggerman, J Huybrechts, E Clynen, K Hens, L Harthoorn, D Van der Horst, C Poulos, A De Loof, L Schoofs. New insights in Adipokinetic Hormone (AKH) precursor processing in Locusta migratoria obtained by capillary liquid chromatography-tandem mass spectrometry. Peptides. 2002 Apr; 23(4):635-44. doi: 10.1016/s0196-9781(01)00657-x. [PMID: 11897382]
  • T Sakaeda, Y Tada, T Sugawara, T Ryu, F Hirose, T Yoshikawa, K Hirano, L Kupczyk-Subotkowska, T J Siahaan, K L Audus, V J Stella. Conjugation with L-Glutamate for in vivo brain drug delivery. Journal of drug targeting. 2001; 9(1):23-37. doi: 10.3109/10611860108995630. [PMID: 11378521]
  • I Rubio-Aliaga, M Boll, H Daniel. Cloning and characterization of the gene encoding the mouse peptide transporter PEPT2. Biochemical and biophysical research communications. 2000 Sep; 276(2):734-41. doi: 10.1006/bbrc.2000.3546. [PMID: 11027540]
  • T Mizuma, A Koyanagi, S Awazu. Intestinal transport and metabolism of glucose-conjugated kyotorphin and cyclic kyotorphin: metabolic degradation is crucial to intestinal absorption of peptide drugs. Biochimica et biophysica acta. 2000 Jun; 1475(1):90-8. doi: 10.1016/s0304-4165(00)00051-9. [PMID: 10806343]
  • H Ueda, M Inoue. In vivo signal transduction of nociceptive response by kyotorphin (tyrosine-arginine) through Galpha(i)- and inositol trisphosphate-mediated Ca(2+) influx. Molecular pharmacology. 2000 Jan; 57(1):108-15. doi: . [PMID: 10617685]
  • T Fujita, T Kishida, N Okada, V Ganapathy, F H Leibach, A Yamamoto. Interaction of kyotorphin and brain peptide transporter in synaptosomes prepared from rat cerebellum: implication of high affinity type H+/peptide transporter PEPT2 mediated transport system. Neuroscience letters. 1999 Aug; 271(2):117-20. doi: 10.1016/s0304-3940(99)00540-6. [PMID: 10477116]
  • U Schroeder, P Sommerfeld, S Ulrich, B A Sabel. Nanoparticle technology for delivery of drugs across the blood-brain barrier. Journal of pharmaceutical sciences. 1998 Nov; 87(11):1305-7. doi: 10.1021/js980084y. [PMID: 9811481]
  • J Y Summy-Long, V Bui, S Gestl, E Koehler-Stec, H Liu, M L Terrell, M Kadekaro. Effects of central injection of kyotorphin and L-arginine on oxytocin and vasopressin release and blood pressure in conscious rats. Brain research bulletin. 1998; 45(4):395-403. doi: 10.1016/s0361-9230(97)00341-9. [PMID: 9527014]
  • S Haseto, T Mizuma, H Ouchi, T Isoda, M Hayashi, S Awazu. Preference of Peyer's patches to jejunal epithelium for intestinal absorption of oligopeptides, tyrosylglycylglycine and D-kyotorphin. Biological & pharmaceutical bulletin. 1997 Sep; 20(9):1024-5. doi: 10.1248/bpb.20.1024. [PMID: 9331991]
  • G Bronnikov, L Dolgacheva, S J Zhang, E Galitovskaya, L Kramarova, V Zinchenko. The effect of neuropeptides kyotorphin and neokyotorphin on proliferation of cultured brown preadipocytes. FEBS letters. 1997 Apr; 407(1):73-7. doi: 10.1016/s0014-5793(97)00298-6. [PMID: 9141484]
  • H Ueda, S Tamura, N Fukushima, T Katada, M Ui, M Satoh. Inositol 1,4,5-trisphosphate-gated calcium transport through plasma membranes in nerve terminals. The Journal of neuroscience : the official journal of the Society for Neuroscience. 1996 May; 16(9):2891-900. doi: NULL. [PMID: 8622120]
  • Iu B Lishmanov, L N Maslov, A V Krylamov, E V Uskina. [The role of endogenous opioid peptides in the mechanisms of the antiarrhythmic effect of adaptation]. Fiziologicheskii zhurnal imeni I.M. Sechenova. 1996 May; 82(5-6):48-52. doi: NULL. [PMID: 9053071]
  • D A Ignat'ev, V I Zagnoĭko, G S Sukhova, V F Bakaneva, V P Sukhov. [Biologically active substances in the tissues of hibernating animals]. Zhurnal obshchei biologii. 1995 Jul; 56(4):450-69. doi: NULL. [PMID: 7483833]
  • D H Kim, B Kim, H S Kim, I S Sohng, K Kobashi. Sulfation of parabens and tyrosylpeptides by bacterial arylsulfate sulfotransferases. Biological & pharmaceutical bulletin. 1994 Oct; 17(10):1326-8. doi: 10.1248/bpb.17.1326. [PMID: 7874051]
  • A Kawabata, S Manabe, H Takagi. Comparison of antinociception induced by supraspinally administered L-arginine and kyotorphin. British journal of pharmacology. 1994 Jul; 112(3):817-22. doi: 10.1111/j.1476-5381.1994.tb13152.x. [PMID: 7921607]
  • S Haseto, H Ouchi, T Isoda, T Mizuma, M Hayashi, S Awazu. Transport of low and high molecular peptides across rabbit Peyer's patches. Pharmaceutical research. 1994 Mar; 11(3):361-4. doi: 10.1023/a:1018948617587. [PMID: 8008699]
  • A J Kee, R C Smith. Organ clearance of tyrosyl-arginine and its effect on amino acid metabolism in young sheep. Metabolism: clinical and experimental. 1993 Aug; 42(8):958-66. doi: 10.1016/0026-0495(93)90007-b. [PMID: 8345819]
  • M Satoh, H Ueda, S Tamura, Y Yoshihara, N Fukushima. Inositol 1,4,5-trisphosphate activates Ca2+ channels in the plasma membranes of rat brain nerve terminals. Advances in experimental medicine and biology. 1991; 287(?):97-110. doi: 10.1007/978-1-4684-5907-4_9. [PMID: 1662018]
  • P Tengamnuay, A K Mitra. Bile salt-fatty acid mixed micelles as nasal absorption promoters of peptides. I. Effects of ionic strength, adjuvant composition, and lipid structure on the nasal absorption of [D-Arg2]kyotorphin. Pharmaceutical research. 1990 Feb; 7(2):127-33. doi: 10.1023/a:1015868516602. [PMID: 2308892]
  • H Ueda, N Fukushima, Y Yoshihara, H Takagi. A Met-enkephalin releaser (kyotorphin)-induced release of plasma membrane-bound Ca2+ from rat brain synaptosomes. Brain research. 1987 Sep; 419(1-2):197-200. doi: 10.1016/0006-8993(87)90583-x. [PMID: 3676725]
  • Y Ito, M Iwaki, T Ogiso, S Nakamura, K Kato, S Sawaki. Inhibition of hydrolytic activities of human dipeptidases toward leukotriene D4 and kyotorphin by captopril. Clinical and experimental hypertension. Part A, Theory and practice. 1987; 9(2-3):681-5. doi: 10.3109/10641968709164242. [PMID: 3301087]
  • T Mitsuma, T Nogimori. Effects of various drugs on thyrotropin secretion in rats. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 1985 Jul; 17(7):337-41. doi: 10.1055/s-2007-1013537. [PMID: 3161812]
  • K Matsubayashi, C Kojima, S Kawajiri, K Ono, T Takegoshi, H Ueda, H Takagi. Hydrolytic deactivation of kyotorphin by the rodent brain homogenates and sera. Journal of pharmacobio-dynamics. 1984 Jul; 7(7):479-84. doi: 10.1248/bpb1978.7.479. [PMID: 6541692]
  • L Giuliani, G Carmignani, E Belgrano, P Puppo. Transcatheter arterial embolization in urological tumors: the use of isobutyl-2-cyanoacrylate. The Journal of urology. 1979 May; 121(5):630-4. doi: 10.1016/s0022-5347(17)56913-x. [PMID: 439260]
  • G Baumann, A Chrambach. Quantitative removal of carrier ampholytes from protein fractions derived from isoelectric focusing. Analytical biochemistry. 1975 Dec; 69(2):649-51. doi: 10.1016/0003-2697(75)90173-6. [PMID: 3125]
  • A C Buck. Disorders of micturition in bacterial prostatitis. Proceedings of the Royal Society of Medicine. 1975 Aug; 68(8):508-11. doi: NULL. [PMID: 681]
  • T Fukushima. [Monoamine oxidase (XXXVI). Characteristics of benzylamine oxidase in the dog serum]. Nihon yakurigaku zasshi. Folia pharmacologica Japonica. 1975 Jul; 71(5):457-62. doi: . [PMID: 280]