Microsomes: Iyo Yakasarudzika muVitro Metabolic Model yekusagadzikana kwezvinodhaka

Microsomes: Iyo Yakasarudzika muVitro Metabolic Model yekusagadzikana kwezvinodhaka

Microsomes: Tsanangudzo uye Mabasa

Muzhinji, microsomes anoreva nezvesimba, vesicular membrane masangano anenge zana nm Iyi ndiyo magungano ekushungurudzika anoenderana nezvikamu zviviri zvakakosha: er membranes uye ribosomes. Microsomes anonyanya kupfumiswa naCytochrome P450 (Cyp450) oxidase enzymes, ayo anotamba chinzvimbo chepfungwa mune oxidative metalosism uye inokatyamadza metlabolism maitiro.

MuVitro, microsomes chengetedza mabasa akakosha eERI, kusanganisira protein synthesis, protein glycosylation, uye inopa chishandiso, chinopa chishandiso chevadzidzi chekufunda akasiyana siyana ebiokimical uye pharmacological maitiro.

Mufananidzo 1: Microsomes (Kwayedza: Internet)

1. Key Organs mune zvinodhaka metabolism

Metabolism metabolism inoreva makemikari anochinja mushonga unoita mukati memuviri, zvichikonzera kugadziriswa kwechimiro. Kuita uku, kunozivikanwawo seBiotransformation, kunyanya kunoitika muzvinyorwa zvakadai seiro chiropa, itsvo, mapapu, matumbu, matumbu, uye ganda. Pakati peizvi, chiropa ndiyo nzvimbo huru yemakurukota edhisheni, ichiteverwa neitsvo seyechipiri yakakosha.

Mukati mechiropa, zvinodhaka - metabolizing enzymes contaly shanduko yekugadzira iyo inogona kuunganidzwa mumatanho maviri: chikamu chandineti chechipiri uye phase II metabolism.

• Chikamu ini metabolism (phase ini zvinogadzirisa): Chikamu ichi chinosanganisira oxidative oxidative Aya maitiro anogona kutungamira kune hepatooricity.
• Chikamu Ii Ii metabolism (Phase II Reaction): Iyi chikamu ine chekuita nekusagadzikana kwekuita, iyo inonyanya kushanda kuti ishandise zvinodhaka. Mushure mekunge metabolism, madhiragi mazhinji anorasikirwa nebasa ravo remapapu, kunyangwe vashoma vangave vanoshanda vamiriri vekurapa.

Chiropa chinobata anenge 70% - 80% yeiyo yakazara zvinodhaka metabolism, inosimbisa basa rayo repakati muBiotransformation.

Pamusoro pechiropa, itsvo dzinopa zvakanyanya kune zvinodhaka metabolism, accounting kweanenge 10% - 20% yehuwandu hwe metabolic chiitiko. Itsvo dzakazara zvinodhaka uye metabolites neye filtration uye secretion. Nekudaro, kugona kwavo kwekuremara kwezvinodhaka kune mashoma, izvo zvinogona kutungamira mukuunganidzwa kwemamwe mishonga uye zvinogona kukanganisa.

Pamusoro pechiropa neitsvo, mamwe mitezo, mamwe mitezo yakadai seyakatemerwa enzyme masisitimu uye mapapu anotambawo basa mukupesvedzera zvinodhaka, kugovera, uye metabolism, albeit kune zvishoma.

Mufananidzo 2: Kugadzirisa kwakachengetedzwa neMookoxygenase (Source: Internet)

2. Key enzymes mune zvinodhaka metabolizing nhengo

Sezvakakurukurwa, metwork yezvinodhaka inonyanya kuenderana nekushanda kwakakodzera kwemasisitimu akasiyana-siyana mune chiropa, itsvo, gastroint turakiti, uye mamwe mitezo. Kunzwisisa iyo enzyematic profiles yeaya nhengo dzakakosha pakudzidza kwakazara kweanodhaka metabolism maitiro.

Enzymes inobatanidzwa mune zvinodhaka metabolism inowanzo kuvezwa mumakirasi maviri: microsomal enzyme masisitimu uye isiri - mikrosomal enzyme masisitimu.

• Microsomal enzyme system:
  Aya ma enzymes anonyanya kuumbwa mumarara emiromo emiromo yeiyo endoplasmic reticulum mune chiropa masero nemamwe masero. Boka rinonyanya kukosha re oxidative enzymes muHepatic microsomes ndiyo Hepatic microsomal yakasanganiswa - basa oxidase system, zvakare inozivikanwa seMonooxygenases (cyp450). Aya ma enzymes anomiririra nzira yekutanga yedhorobha remushonga mumuviri, rinogona kutengesa huwandu hwakawanda hwekuita oxidative maitiro. Biotransformation procalyzed neaya enzymes inoda kubatanidzwa kweCytochrome P450 (MGULELME II, MG²⁺, Flachuretein, Kwete - Heme Dord mapuroteni, uye zvimwe zvekushandisa.
  Pamusoro pezvo, UDP - Gluculonosyltransfansfansfansfanes (Ugts), chikamu chakakosha cheChikamu cheComInalm
• Kwete - microsomal enzyme system:
  Zvakare zvinozivikanwa seType II enzymes, izvi zvinosanganisira maatts, sulfotransferases (Sulfotransferases (Sulfotransferases (Sulfathione - s - Trats), n - acetyltransferases ( Kwete - midzika enzymis inonyanya kufambisa chikamu chei Ii metabolism.

Kupfuura kwayo basa rayo remuviri mukuchengetedza mvura uye electrolyte chiyero uye kuwedzera zvinhu zvinhu, iyo itsvo iri zvakare chinhu chakakosha cheshuwa ini neChikamu Ii metabolic byransformations.

• Chikamu chandineti muitsvo:
  Inosanganisira P450 enzymes, kushomeka kwemvura, uye akasiyana monygenasases, kunyangwe zviitiko zvavo zvakadzikira zvakanyanya pane izvo zvechiropa, zvichiita nhambo yetsvo, ini metherelism isinganyanyo.
• Phase II metabolism muitsvo:
  Zvikurukuru zvinosanganisira maatts, zvinotwadza, maGSTs, nats, uye amino acid inosimudzira enzymes, ichiridza chikamu chikuru muRenal zvinodhaka metabolism.

Mbiru, seimwe yemitezo mikuru yekugaya, inoitawo basa rinorwadza mune zvinodhaka. Mu turakiti remukati, zvinodhaka zvakawanda pasi pe metabolic maitiro anovashandura kuita zvakanyanya uye anobviswa metabolites. Aya metabolic maitiro anoitika kuburikidza nenzira mbiri:

1. Enzymatic metabolism yemukati mepitenal epithelial masero, ayo anosanganisira enzymes akadai saCyp450, maatts, uye miromo.
2. Microbial - Yakareverwa metabolism ine mudumbu microbiota.

Pamwe chete, idzi enzyematic system mune dzakasiyana mitezo inopa iyo inoshanda metabolism uye kubvumidzwa zvinodhaka, zvichiratidza kuoma uye kudengenyeka uye kuunganidzwa kwemishonga yemugodhi mumuviri.

Nekudaro, nekuenderera mberi kwekufambira mberi mumushonga, zvinodhaka zvakakanganisika zvakanyanya mumakore apfuura nekuda kwekukurumidza kwekukurumidza, kukurumidza kutanga kwechiito, uye kugona kupfuura kutanga - Pass Passetism. Kusiyana nemishonga yemuromo mishonga, mafomu enharu kununura mishonga yakananga kune iyo pulmonary tishu, ichidzivisa hepatic kutanga - Pass Mhedzisiro. Izvi zvinoratidza kukosha kwekuongorora zvinodhaka metabolism mukati memapapu ekupembera mafomu.

Mapapu ane akasiyana-siyana drug - Pakati peizvi, Pulmonary P450 enzymes anotamba chinzvimbo chakakosha muBiotransformation yeXenobiotformation

Mukupfupikisa,Drug metabolism mukati memuviri kazhinji inowanzoitwa chirongwa chakarongeka chinosanganisira nhengo dzakawanda uye enzyme masisitimu. Saka, mukati merimwe nguva yekutanga inodhaka yekubudirira

3. Mu vitro zvinodhaka metabolism mhando: microsomes

Kuenzaniswa neVivo muVivo Metabolism Studies, muVitro Ons Ongorora kuderedza kupindira kubva pazvinhu zvehupombwe, kubvumira kutarisisa kwakananga kwekudyidzana pakati pemishonga uye enzymes. Nekuda kweizvozvo, mu vitro metabolism mhando dzave sarudzo dzinosarudzwa panguva yekutanga zvinodhaka. Mhando dzakajairika dzeVitro zvinodhaka metawa Yakapihwa kuti chiropa chiri chikuru saiti yedhisheni metabolism, masero ezvipenga uye zvadzo zvakavanzika-senge chiropa microsomes, chiropa s9 zvidimbu, chiropa tishu homogenates, uye chiropa cysotosol-ndiwo mhando dzekufunda dzekufunda zvinodhaka metabolism.

Microsomes, zvakananga, ndezvesicular membrane zvivakwa zvinobva zvakakamurwa kubva kuChepplasmic retollum iyo pachako - Ungana panguva yeCell Homogenization uye Musiyano Centrifization. Ivo vanogovaniswa zvakanyanya mune nhengo dzakadai seiro chiropa, itsvo, matumbo, nemapapu. Sezvo microsomes ine phazy i enzymes se cytochrome p450 (yeI phaishi) uye chikamu II enzymes sewatts uye stocompar yakawandisa nzira ye metabolic yemishonga dzakasiyana siyana. Nekudaro, kusarudza tishu

Uyezve, maererano nehungwaru hwehunyanzvi hwezvidzidzo zvePharmacinicicic zvidzidzo zvezvinodhaka, mhuka dzinoedza dzakadai semakonzo, makonzo, nguruve, miniature nguruve, uye nyani dzinowanzo shandiswa. Zvemadhiraivha madhiragi, kanokwana maviri anofanirwa kushandirwa, neyakagadzirwa neyakagadzirwa uye imwe isiri - yetsiva. Kupfuura mhuka dzemhuka, zvinhu zvinowanikwa-senge chiropa chevanhu chovaridzi-vanosimbiswawo sekiyi zvishandiso zveisiriclinical adme zvidzidzo. Nekuda kweizvozvo, kusarudza microsomes kubva kumarudzi akawanda, kusanganisira vanhu, itsvimbo inokosha mukutsvaga zvinodhaka.

Muchiedza cheizvi,Ifase, Somutungamiri anotungamira muVitro Biological Re reagents, akabudirira kugadzira zvigadzirwa zvemukati zvinobva mumatisirwo akasiyana siyana emarudzi akawanda, kusanganisira vanhu, mbeva, makonzo, makonzo, uye makonzo, uye makonzo, uye makonzo, uye makonzo, uye makonzo, uye makonzo, uye makonzo, uye makonzo, uye makonzo, uye makonzo uye makonzo. Zvigadzirwa izvi zvinopa dzakasiyana siyana sarudzo dzezvidzidzo pane mhando misiyano, metabolic kugadzikana, P450 inhibition, uye metabolic enzyme phenototing.

Nezvemhando yepamusoro yekutonga, Iphase inovimbisa kuvimbika kwechigadzirwa, kubatsira vatengi chengetedza nguva uye kugadzirisa kushanda zvakanaka. Microreomes ndiyo yakanakira sarudzo yekuVitro nonclintical kutsvagisa.

Zvakanakira zveTipsese zvigadzirwa:

• Kuteerana:Zvese matishu anoshandiswa mukugadzirwa anoteurwa kuburikidza neCistified Channels neakajeka kuturika.
• Kuchengetedza:Kugadzira matishu kunoedzwa kune vatengesi kuti vave nechokwadi chechigadzirwa mhando uye kuchengetedzwa.
• Mhando yepamusoro:Zvigadzirwa zvinotsemesa zvemukati zvemukati zvekutonga, chengetedza hombe batch saizi ine mashoma internet - batch kusiyana-siyana.
• DZIDZISO:Yakagadzirwa microsome zvigadzirwa kubva kune yakatarwa mhando kana matishu anowanikwa kuti asangane zvakasiyana zvemutengi zvinodiwa.

Lowing Makore eR & D Nyanzvi,Ifaseyaunza yakakwira - Grea Repreats Reagents paminda yakawanda uye mapoka. Zvigadzirwa izvi zvinoshanda sezvishandiso zvakakosha zvekutanga - Stage Kubudirira kwezvinodhaka, kupa zvinhu zvitsva, nzira, uye maitiro ekuongorora masasa sainzi. Ivo vanopawo mhinduro dzakareruka dzezvidzidzo zvekutengesa zvinhu muchikafu, mishonga yemishonga, uye makemikari.

Tinotarisira kutarisira vanotsigira vanoongorora nezvinhu zvedu zvatakavimbika uye zvakavimbika!



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