Ma Microsomes Okhazikika Pakatikati: Udindo wa gawo ine metabolism ndi gawo ii kagayika

Iphase Biosciunces Zogulitsa

Ma Micceromes ndi misewu yosiyanasiyana yochokera ku endoplasmic retiiculum ya endoplasmic yosokoneza maselo, makamaka ma hepatocytes (ma cell a chiwindi). Amakhala olemera mankhwala - michere yosuta, makamaka banja la cytochrome p450 (lomwe la Cyp), lomwe limagwira ntchito yofunika kwambiri yazakudya zingapo. Kukhazikika kwa metabolific kugwiritsidwa ntchito ma microsomes ndi ofunika kwambiri pakupanga mankhwala oyambilira chifukwa amathandizira kuneneratu ku Vivo Phalcokinetics. Mwa kuyeza kuchuluka kwa kagayidwe mu vitro, ofufuza amatha kuwerengera chidwi chofuna kudziwa momwe mungafunire kuti anthu azichita zinthu mwa anthu. Nkhani yotereyi siyingowonjezera kuwunika kwa mankhwala ambiri ochulukirapo - mwadzidzidzi komanso kuthandiza pozindikiritsa mikangano ya kagayidwe ndi mankhwala omwe mungagwiritse ntchito mankhwala. Kuphatikiza kwa microsomes kuchokera ku misempha zosiyanasiyana kumalola kumvetsetsa kwathunthu kwa onse a hepatic ndi zowonjezera, zomwe ndizofunikira kuti mutseke zopangidwa ndi mankhwala musanayesedwe. Ma microsome wamba mkatiKukhazikika kwa metabolismGawani nawonso:chiwindi microsome, maintsume microsome / matumbo a microsome, m'munsi microsome, impso microsome.

Microolumes

Microolumesali olemera kwambiri mu cytochrome p450 michere ndi oxidore yogwirizana. Zinthu zawo zapamwamba zimapangitsa ma microsies a chiwindi omwe amakonda kusintha kagayidwe kachakudya. Panthawi yoyesa, wosankhidwa mankhwala ali ndi ma mitima a chiwindi pamaso pa wofunikira monga Nadph, ndipo kuchuluka kwa kholo pagawo la kholo kumayang'aniridwa nthawi yayitali. Zomwe zimathandizidwa pakuyesera izi zimagwiritsidwa ntchito kuwerengetsa chilolezo, gawo lofunikira lomwe limathandizira kuneneratu kuti mankhwalawa angathetsedwe mwachangu bwanji ku Vivo. Chifukwa ma mitima a chiwindi amatha kuperekedwa kwa opereka ambiri, amapereka dongosolo lodalirika komanso loletsa lomwe limachepetsa kusintha kwazinthu zachilengedwe.

Matumbo microsomes / matumbo microsomes

Matumbo microsome, nthawi zina amadziwikanso kutimatumbo microsome, ngakhale osachulukana mu metabelic enzymes poyerekeza ndi anzawo a Hepatic, ndizofunikira chimodzimodzi munthawi yoyamba - Patulani kagayidwe. Pambuyo m`kamwa makonzedwe, mankhwala ayenera kudutsa khoma lamatumbo lomwe limasinthiratu kusintha kwakukulu kwa enzymati musanafike kufalikira kwadongosolo. Ntchito ya metabolic m'thupi m'matumbo imatha kuthandiza kwambiri bioagaluty wa mankhwala, ndipo deta yomwe idapezekapo ndi yofunika pakupanga njira zopangira kuthana ndi prebolism.

Ma microsomes

Chikumba ma microsomesamakonzedwa kuchokera ku minofu yakhungu ndikuwonetsa mankhwala - Zochita zolimbitsa thupi, kuphatikizapo za ma enp michere. Ngakhale kuti enzymatic ntchito yapakhungu imakhala yochepera 10% ya omwe amapezeka m'chiwindi, khungu limachita mbali yofunika kwambiri ku biotransformation ya mabiodermal xenobiotic. Pogwiritsa ntchito microsomes ya khungu m'maganizo imatha kupereka chidziwitso cholowera kagayidwe ka mankhwala omwe amagwiritsidwa ntchito kapena amalowetsedwa pakhungu.

PhapoMa microsomes

Ma Microsomesamakonzedwa kuchokera ku minyewa ya ma pulmonary ndipo amagwiritsidwa ntchito kufufuza kagayidwe ka mankhwala omwe amathandizidwa kudzera mu inhalation kapena zomwe zimayambitsa kupuma. Ngakhale ndende ya cytochrome p450 michere imatsika kuposa chiwindi, mapapu amakhalabe tsamba lotsutsa kagayidwe ka poizoni ndi mankhwala osokoneza bongo. Mtunduwu ndi wofunika kwambiri pakuwunika minofu - Mapangidwe apakati pa kagayidwe ka kagayidwe ka kagayidwe kazinthu.

Ma Microsomes

Ma Microsomesamadzipatula ku impso zimakhala ndikupereka chidziwitso pakupanga kagayidwe kachakudya komwe kumachitika mu impso. Popeza impso si chiwalo chokha chazomwe zimathandizira pakugwiritsa ntchito kagayidwe ka mankhwala ena, kugwiritsa ntchito migluomes ya impso pamalo opunthira kumapangitsa ofufuza kuti awone ofufuza omwe amatha kulumikizidwa ndi nephrotoxicity. Mwanjira imeneyi, ma millions Microsomes omwe amakwaniritsa deta kuchokera ku chiwindi ndi matchuthi, ndikupereka mawonekedwe owonjezera pa metabolic.

Ma distis microsomes

Telasis ma microsomesamachokera ku testicular minodi ya testicular ndipo amakhala ndi ma enzymes omwe amayambitsa kupembedzera komanso ma exounous. Ngakhale osagwiritsidwa ntchito kawirikawiri kuposa ma mitimas a chiwindi, amatha kukhala ofunika pakuphunzira kagamba cha zinthu zomwe zimakhudza thanzi la amuna. Zambiri mwatsatanetsatane pakugwiritsa ntchito kwawo mu metabolic zokhazikika pamalingaliro ndizochepa ndipo zimatha kukhala zosiyanasiyana kutengera kafukufuku.

Ma Microsomes a Epididymis

Embolidlimis ma microsomesamapezeka kuchokera ku minofu ya epidalmal ndipo, monga ma microsomes microsomes, amatenga nawo mbali mu kagayidwe kazinthu zina. Kugwiritsa ntchito kwawo mu metabolific ma camebolictions sikuli komweko, koma atha kugwiritsidwa ntchito mu kafukufuku wofufuza kagayidwe kazinthu zomwe zimapangitsa kubereka mwamphamvu komanso kubereka. Protocols yatsatanetsatane ndi kugwiritsa ntchito zimadalira zolinga za kafukufukuyu.

Gawo I Metabolism & Nadph Regearch System

Gawo I Metabolic InasinthaAmayang'aniridwa makamaka ndi ma enp michere, ndipo zotsatirazi zimafunikira kuperewera kosalekeza kuchepetsa zofanana mu mawonekedwe a NADP. Kuwonetsetsa kuti nadph amapezeka nthawi yonse ya makulitsidwe, aNTHAWI YOTHANDIZAamawonjezeredwa ku lingaliro. ANTHAWI YOTHANDIZANthawi zambiri zimaphatikizapo nadp⁺, shuga - 6 - - - - - enzyme, ndi enzyme shuga - 6 - Kusinthika kumeneku ndikofunikira chifukwa imathandizira kuti redox zisamayende ndi ma enp enzymes, kulola ma microsomes kuti asunge zochitika zawo kwakanthawi.

Mkuyu 1. Gawo lomwe ndimachita phazi la metabolism
Gawo la II Metabolism & Ugt Guble System

Pomwe microomes microsomes imakhudzana kwambiri ndiGawo I Metabolism, amathanso kusinthidwa kuti aphunzireGawo II Metabolism Aganizidwemonga gluculanidation. Glucuronidation ndi njira yolumikizirana ndi Uridine 5 '- Dephatho Crostransfetrase (Ugt) ma syzymes, omwe amatha kuphatikiza glucuronic acids kapena gawo lawo metabolites. Kuwongolera glucuronidation mu lingaliro la microsomal, aMakina a Ugtndi woyambitsa ma voctor Udp - Glucuronic acid (UDPGA) Amawonjezeredwa. Dongosolo la Ugt Matendawa nthawi zambiri limakhala ndi UDPGA, mapuloteni a procymidin ndi d - Glucuronosyl - 1.4 - lactolone. Popeza michere ya Ugt ndi membrane - omangidwa ndipo sangakhale ocheperako ku Microsome, Pore - kupanga wothandizira ngati Alamethicin nthawi zina kumaphatikizidwa nthawi zina. Alamethicnin imawonjezera kuchuluka kwa ma microsomal membranes, motero amalimbikitsa kulowa kwa UDPGGA ku UGT michere ndikusintha njira ya mabungwe.

Kukuku kwa mkuyu. Zochitika ndi zinthu zoyika za gawo la mankhwalawa.

Doffer Dongosolo

Machitidwe onse,0.1m PbsBuffer amatenga gawo lofunikira pakukhazikika ndi ntchito ya ma enzymes. Makina obisika awa amapereka chilengedwe chokhazikika Ph ndi chilengedwe chokhazikika chosungira umphumphu wa onse cyp ndi ugt michere. Mitundu yosasinthika yomwe imaperekedwa ndi 0.1m PBs Press ikuwonetsetsa kuti izi zimachitika m'njira yolamulidwa, kuthandizira muyeso wodalirika wa kukhazikika kwa kachakudya ndi chilolezo.

Mitundu yosiyanasiyana yama microsomes

Anthu microsoome

Ma Microsomes aumunthuNdiwo chonenepa kwambiri mu kachakudya chokhazikika pamalingaliro osokoneza bongo, pamene amasintha kwambiri chilengedwe cha anthu. Michere ya anthu ya chiwindi imakhala ndi michere yambiri ya cytochrome ya c450, yomwe imayang'anira gawo lomwe ndimagwiritsa ntchito mankhwala ambiri. Misewu yama microsomes imagwiritsidwa ntchito kwambiri poyesa metabolism ya anthu, kuphatikizapo enzyme - Kukhazikika kwa mankhwalawa, kukhazikika kwa metabolic, komanso chizindikiritso cha metabolites. Kugwiritsa ntchito kwawo ndikofunikira ku koyambirira - Gawo Kukula kwa mankhwalawa kuti muwonetsetse kuti phula limakhala ndi pharmacokinetics zabwino mwa anthu, ndi chidwi chopewa chiwopsezo cha chiwindi kapena zovuta zina.

NAT - Anthu A Driver Armage Microsomes

NAT - Anthu Amtundu Wamtundu Waumunthu, Nthawi zambiriNyani wa Monkey Monkey Liver Mitimas, Marmostss Monkey Liver Microsomes, anyani a CynomolcusMa Microomes a chiwindi, amagwiritsidwa ntchito mu kapangidwe ka kapangidwe kamene kali ndi kafukufuku kuti awone momwe mankhwalawa amapangidwira ndi michere mu chiwindi. Microsomes iyi imakhala ndi ma entochrome P450 michere ndi mapuloteni ena a kagayidwe omwe amathandizira gawo la mankhwala osokoneza bongo. ONSE - Akuluakulu a anthu ndiofunika kwambiri pamaphunziro a chiwindi chifukwa cha chiwindi chofanana ndi anthu, ndikupanga chida chofunikira powunikira mankhwala, komanso kufooka kwa mankhwala atsopano asanayesedwe. Amapereka zambiri zothandiza pa anthu - monga metabolism poyerekeza ndi makoswe, kukonza kulondola kwa mankhwala osokoneza bongo

Galu chiwindi microsome

Agalu, makamaka agalu a Groagle, amagwiritsidwa ntchito poyambira toxicology ndi masitima a pharmacokinetic.Agalu a chiwindiM'malo mwake, makamaka omwe achokera ku chiwindi, ndi zida zofunika kuti mumvetsetse momwe mankhwala angapangitsire mankhwala omwe sangakhale - Zinyama zokongola.Canine Liver MicrosomesNthawi zambiri amagwiritsidwa ntchito poyesa chitetezo kuti athe kuwunika kagayidwe ka metabolic komanso kuthekera kwa mankhwala - mankhwala osokoneza bongo. Ma Microsomes awa amathanso kuneneratu momwe mankhwala amaphatikizira komanso kukonzedwa mwa anthu, kupereka chidziwitso pakusiyana kwa anthu ndi agalu mogwirizana ndi kagayidwe ka mankhwala.

Rat udr microsome

Makoswe ndi amodzi mwa nyama zomwe zimagwiritsidwa ntchito kwambiri pa kafukufuku wamankhwala komanso woopsa, ndipo ma microsomes awo a chiwindi ndiofunikira mu kachakudya.Ma microomesNthawi zambiri amagwiritsidwa ntchito moyambirira ku - mankhwala osokoneza bongo kuti athetse kagayidwe ka mankhwala oyesera, chifukwa njira zawo za metabolic zili bwino - Zomvetsetsa. Ngakhale makoswe amagawana mikangano ingapo ndi anthu, pali kusiyana kwakukulu mu ntchito ya enzyme, makamaka polemekeza ma enzyme a c450. Mitima ya makoswe nthawi zambiri imagwiritsidwa ntchito kuyesa kukhazikika kwa kagayidwe ka ma metabolic ndikuwunika zovuta za pharmacokinetic, monga mitengo yovomerezeka ndi bioavailability.

Mbewa microsome

Zofanana ndi makoswe, mbewa imagwiritsidwa ntchito kwambiri pakufufuza, ndi microsomes imagwira ntchito yofunika kwambiri pakukhazikika pa metabolic. Ma mbewa amakhala amtengo wapatali pophunzira kusiyanasiyana kwa ma genetic mu metabolism chifukwa cha vuto lawo - Makhalidwe Abwino.Mbewa ya mbewaMuli ndi ma enzymer a c450, omwe amawapangitsa kukhala othandiza powunikira momwe mankhwala angapangitsire mitundu yosiyanasiyana yama ma gejini osiyanasiyana. Zina mwa mbewa, ball / C maliseche, zimadziwika kuti ndi zovuta zomwe zimasowa macymus, ndikuwapangitsa kukhala Immunodesiya. Pogwiritsa ntchitoBalb / C Naude Liver Microsomes, ofufuza amatha kuwunika momwe mankhwala kapena kuphatikizira amapangidwira, kuchuluka kwa biotransform, ndipo kukhazikika kwake m'chiwindi, komwe ndikofunikira kulosera za pharmacokinetics mwa anthu. Komabe, mbewa zimakhala ndi njira zina zosiyanirana ndi anthu, kutanthauza kuti deta yochokera ku minyewa ya mbewa iyenera kutanthauziridwa mosamala akamaneneratu za kagayidwe ka anthu. Microsomes nthawi zambiri imagwiritsidwa ntchito kwambiri - Kupumira kwa kuwunika kuti mudziwe zambiri za mankhwala mwachangu.

Hamster Liverr Microsome

Hamsters, makamaka kwambiri a Syrian hamsters, nthawi zambiri amagwiritsidwa ntchito mu kafukufuku wa metabolic chifukwa cha mikhalidwe yawo yapadera.Hamster chiwindiNdizothandiza pakuwunika kagayidwe ka mankhwala ndi kununkhira, makamaka pazopanga zomwe zingawonetse mitundu - zolemba zapakatikati. Ma Microomes nthawi zambiri amagwiritsidwa ntchito pophunzira momwe mankhwala amathandizo amapangidwira m'madzi ang'onoang'ono, ndikupereka ma aivatura m'njira za metabolics zomwe sizingamvetsetsedwe mokwanira m'mitundu ina.

Gerbillinae chiwindi

Gerbillinae chiwindiAmachokera ku majeretisi, mitundu yaying'ono ya nyama yaim yomwe imagwiritsidwa ntchito poyambira toxicology ndi kafukufuku wamankhwala. Mu kapangidwe kachakudya chokhazikika, ma micbillinae chiwindi cha ku Gerbillinae amagwiritsidwa ntchito kuti athe kuwunika momwe chiwindi chimakhalira ndi michere ya microsomal, makamaka ma enzyme. Maganizo awa amathandizira kudziwa kukhazikika kwa kagayidwe ka mankhwala kapena mankhwala, kuwunika kuthekera kwawo kwa biotransfornation ndikuchotsa. Gerbils nthawi zina amagwiritsidwa ntchito pamaphunzirowa chifukwa cha mbiri yawo ya kagayidwe kachakudya, yomwe imatha kupereka chidziwitso cha mitundu - Kusiyana kwapadera mu kagayidwe ka mankhwala.

Minipig chiwindi microsome

Mipata ikukula yotchuka mu pharmacokinetic ndi zoopsa zamagetsi chifukwa chofanana ndi anthu omwe amapezeka pathupi.Minipig chiwindiNthawi zambiri amagwiritsidwa ntchito mu metabolic yokhazikika pamalingaliro kuti apereke deta yomwe imafanana kwambiri ndi mankhwala osokoneza bongo poyerekeza ndi mitundu yokongola. Mitima ya microomes ndi yofunika kwambiri pophunzira kuyamwa mankhwala oyamwa mankhwala, kugawa, komanso mawu (ADME) muchilengedwe wokhala ndi metabolic. Mipaugs ndiofunika kwambiri pakuwunikira zinthu zomwe zimafunikira kulosera kolondola kwa mayankho a metabolic.

Guniea nkhumba microsomes

Mosiyana ndi makoswe ena, nkhumba za Guinea sizimadwala - Michere yosungunuka, monga cytochrome p450 2D, yomwe imatha kukhudza momwe amasinthira mankhwala. Izi zimapangaGuinea nkhumba microomesMakamaka kothandiza kuphunzira mitundu ya mitundu - Kusiyana kwapadera mu mankhwala osokoneza bongo. Mbiri yawo yapadera ya enzyme imatha kupereka malingaliro mu mtundu womwe umakhalamo m'mitundu yambiri, ndipo imatha kuwunikira miyala yocheperako, ndipo imatha kuwunikiranso zoopsa zomwe zingachitike popanga mankhwala omwe mwina sangawonedwe mu mitundu ina. Izi zimapangitsa nkhumba za Guinea ndizofunikira poyerekeza ndi ma toxicology ndi maphunziro a pharmacokinetic.

Feline Liver Microsome

Feline Liver Microsomesamagwiritsidwa ntchito mu kafukufuku wa metabolic kuti awone momwe mankhwala amapangidwira mumphaka. Amphaka ali ndi mawonekedwe apadera a kasoti, kuphatikizapo ntchito zochepa gluculosination, zomwe zingakhudze kagayidwe ka mankhwala ena. Chifukwa cha izi,Mphaka wa Mphaka wa Mphakandizofunikira pophunzira momwe mankhwala achilengedwe amakhalira mwa amphaka, makamaka chifukwa cha zowona zam'madzi. Amagwiritsidwa ntchito poyesa zoopsa kapena nkhani za metabolic mu mankhwala omwe amagwiritsidwa ntchito ndi kuwunika kwa felerspecpec misatabolism posintha kwa anthu kupita ku maphunziro a nyama.

Bovine Liver Microsome

Bovine Liver Microsomes, wochokera ku ng'ombe, ndizothandiza kwambiri pophunzira kagayidwe ka mankhwala ogwiritsa ntchito ziweto. Ng'ombe zimakhala ndi njira zosiyanasiyana za kagayidwe poyerekeza ndi anthu, makamaka pa ntchito ya michere ina yomwe ikugwira ntchito m'gulu la kagayidwe. Bovine chiwindi microsomes amagwiritsidwa ntchito kulosera momwe mankhwala opangira zoyatsira zakudya kapena azaulimi amapangidwira ng'ombe. Kuphatikiza apo, microsomes iyi imagwiritsidwa ntchito kuti ifufuze zotsalira mu nyama ndi mkaka, kuthandiza kuwonetsetsa kuti chakudya cha anthu. Ngakhale ma microsomes a Bovine amapereka deta yofunikira pa ziweto, nthawi zambiri sizigwiritsidwa ntchito mwachindunji ku mankhwala osokoneza bongo chifukwa cha kusiyana kofunikira kagayidwe. Kuwonjezera pa bovine,Hatchi Haver Microsome,Nkhosa microsomesndimbuzi ya mbuziamagwiritsidwa ntchito kwambiri.

Nkhuru Liverr Microsome

Ma Microsomes, pomwe samagwiritsidwa ntchito kawirikawiri kuposa omwe amachokera ku zolengedwa, amatha kukhala othandiza mu maphunziro a mankhwala kagayidwe. Mitima yam'madzi yodziwika ndiMa Microomes,Ma Micromes a nkhuku,Turkey Liver Microsomesndizitsamba za ziwiya. amalemba ntchito kuti ayese momwe mankhwala angakonzedwe mu mitundu ya avian. Izi ndizofunikira makamaka pakukula kwa zakudya za nkhuku za nkhuku, komanso maphunziro azachilengedwe kuti mumvetsetse kagayidwe ka mankhwala omwe angalowe mu chakudya kudzera mbalame.

Nsomba chiwindi microsome

Nsomba za chiwindi, makamaka utawalezaMicrout microsomes, amagwiritsidwa ntchito pofufuza zachilengedwe komanso zosokoneza bongo. Nsomba zimakonda kwambiri zodetsa zachilengedwe, ndipo ma microsomes awo a chiwindi ndi zida zofunika pophunzira njira za kagayidwe kachakudya chomwe chimakhudzidwa ndi zodetsa zachilengedwe zam'madzi. Ma Microsomes A nsomba amagwiritsidwanso ntchito pophunzira chilengedwe cha mankhwala opangira mankhwala ndi mankhwala azaumoyo, kuthandiza kupenda kuthekera kwa bioacculamp ndikukhudza moyo wa kuoneka. 

Mapeto

Ma Microsomes amatenga gawo lofunikira kwambiri m'magawo oyamba a mankhwala popereka chidziwitso chofunikira mu kagayidwe kachakudya ndi pharmacokinetics of mankhwala osokoneza bongo. Pogwiritsa ntchito ma microsomal a Ma Microsomal, ofufuza amatha kuwunika gawo i ndi gawo la metabolic. Kupezeka kwa minyeyo yamitundu yosiyanasiyana, kuphatikizapo anthu ndi nyama, kumapangitsa kuti pakhale mtanda - mitundu yosiyanasiyana yofananira, imakulitsa kuneneratu kwa kagayidwe ka mankhwala m'magulu. Pamene njira zopangira mankhwala zimapitilirabe kusintha, microsomal mic imakhala chida chofunikira pakutsata mankhwala opindulitsa komanso ogwira mtima.

Mawu osakira: Kukhazikika kwa metabolism, gawo ine kagayidwe, gawo lomwe limachitika, ma microsomes, ma microsomes, ma microsomes, ma microsomes, ugt makulitsidwe Dongosolo, udpga, 0.1m Pbs, Tris - Microolumes Ashroomes, microsomes microsomes, microsomes microsomes, ma microsomes, Gerbillinae chiwindi ma microsomes, Brub Gun Living Microsomes Microsomes Microsomes Microsomes Microsig Microsomes, Mphaka Ma Microsomes, Bovine Living Microomes, Bovine Living Microomes, Hamster Living Borosomes, Kalulu Wina Ma Microsomes, Turkey chiwindi chiwindi, chiwindi cha Mataval Microsome, Nkhosa Microsies, Boat Living Microsomes, Zitsamba za ziwiya
Kuchulidwa
O 2 onyamula oyendetsa o 2 mayendedwe a hepatic hollow bicloor - Chithunzi cha sayansi pa Rearkuate. Kupezeka kuchokera ku:https://www.esarsarcate.net/figure/phase-i- - --_FIg4_267837256
Kusiyanitsa Zomwe Gawo Lachi Metabolites a Ibuprofen ndi Enaads ena okhala ndi mapulote a plasma plasma - Chithunzi cha sayansi pa Rearkuate. Kupezeka kuchokera ku: https://www.esarsarcate.net/figure/theofts-andsphactic - -265787199