Kugwiritsa ntchito cytochrome p450 (cyp450) ndi UDP - Glucuronosytransit (Ugt) Maphunziro a Milnotype Phenotype ndi enzyme

Mawu ofunikira: Mankhwala - Kulumikizana Mankhwala (DDI), Cytochrome P450 Enzyme Phunziro la Cyzyme), Cyp2c6, Cyp2C19, Cyp2D6, Cyp3a4 / 5, cyp2a6, cyp2e1, Ugt1a1, Ugt1a2, Ugt1a1, Ugt1a1, Ugt1b7, Ugt2B2b17.

• Iphase

Chidziwitso: Cyp enzyme nthawi zambiri imagwiritsidwa ntchito ndiNTHAWI YOTHANDIZA/ NadphndiMa pbs
Ma enzyme a Ugt nthawi zambiri amagwiritsidwa ntchito ndiMakina a Ugtndi Pbs.

Metabolism imagwira ntchito yofunika kwambiri pampando wa mankhwala, zomwe zimakhudza kutaya kwawo thupi komanso momwe zimapangidwira kuwonetsedwa ndi komwe kumachitika. Izi zimachitika makamaka m'chiwindi, koma zitha kuchitikanso ziwalo zowonjezera. Kafukufuku waposachedwa wavumbulutsa tanthauzo la kukhalapo ndi magwiridwe antchito a michere ya mankhwala osokoneza bongo (DME) mu ubongo.Cytochrome p450 enzyme (cyp)ndiUDP - Glucuronosytransferase (Ugt) ndi otenga nawo gawo ofunikira ku Biotransform mkati mwa dongosolo lapakatikati (CNS).

• Cytochrome P450 (CYP)

Cytochrome P450 ikulamulira gawo i kagayidwe (oxidation, kuchepetsa, hydrolysis), kuwerengera zoposa 75% ya kagayidwe ka mankhwala. Mitundu yofunikira imaphatikizapo cyp3a4 (50% metabolism) ndi cyp2d6 (20% metabolism). Cyp imatembenuza mankhwala a Lipophilic kukhala polartabolites, kulimbikitsa kuwala.

A Shepatocytes wamkulu ndi hepatocytes molunjika kuchokera kwa anthu kapena chiwindi, ndipo akhala chitsanzo chofufuzira mankhwala chifukwa chosungidwa ndi zochitika za cyz enzyme ndi njira zathupi. Mtundu woyamba wa hepatocytes ndiye mtundu wowunikira kwambiri wowunika kwa cyp enzyme infutions, academia, ndi mabungwe owongolera. Monga momwe ma cell, hepatocyte ya anthu imapangidwa ndi ma rentitor olandila nyukiliya, corgenti, komanso olimbikitsa, komanso ma metabolis omwe amagwiritsa ntchito mankhwalawa.

• UDP - Glucuronosytransferase (Ugt)

UDP - Glucuronosyltranstsvuteses ndi gawo loyamba la encyme lomwe limagwiritsa ntchito glucuronic acid kukhala opereka matenda a acid a acid ndi zinthu zochulukirapo ndi magulu a polar, omwe amalimbikitsa chilolezo. UGT yaumunthu imagawidwa kwambiri ndikufotokozedwa mu minofu monga chiwindi, matumbo ang'onoang'ono, m'mimba, m'mimba, m'mimba, m'mimba, m'mimba, m'mimba, m'mimba, m'mimba, m'mimba, Mimba. Chiwindi ndi chiwalo chachikulu mu thupi la munthu lomwe limakhala ndi glucuronic acid amamanga zitsamba, ndipo backspes yambiri imafotokozedwa mu chiwindi. Ugt1a7, Ugt1a8, Ugt1a10, ndi Ugt2a1 imagawidwa minofu yazinthu zowonjezera, ndipo glucuronic acid imalumikizana ndi minyewa yazomwe zimachitika makamaka zokhudzana ndi mankhwala osokoneza bongo.

• Ntchito zazikulu pakupanga mankhwala

Mu mtundu wa vitro: Cyp kapena ugt michere monga ma microsomes / hepatocytes oyeserera a Microsome / theka la mankhwala - Kugwiritsa ntchito ma cell kulosera kulosera kwa mankhwala camekical.

Mankhwala - Kulumikizana Mabala (DDI)Phunziro: Khazikitsani zoletsa ku Cyp kuti mudziwe ngati mankhwala osokoneza bongo amaletsa michere ya cyp (monga cyp3a4, cyp2c9) ndikulosera chiopsezo cha DDI. Khazikitsani zoletsa kuipitsa kuyesa kuyesa kuwunika mankhwala osokoneza bongo pa ugt ntchito. Kuzindikira zotsatira za mankhwala osokoneza bongo pa cyp / ugt kudzera pakusanthula kwa hepatocytes.

Njira Zachitukuko Zachilengedwe: Kafukufuku wa ma enp ndi ugt amagwira ntchito yovuta kwambiri mu kapangidwe ka mankhwala ndi kutsimikizika kwa mankhwala osokoneza bongo ndi pharmackinetic (DMP). Gwiritsani ntchito matrict azofachi okhala ndi cyp / ugt metabolites (monga Bile ndi plasma) ya matrix gratary, kusankha njira, ndikupewa zotsatira za ion.

Kafukufuku wa ma gelymorphism: Ugt1a1 ndi majini ena omwe amawongolera enzyme mawu ndi majini ofunikira omwe amakhudzidwa ndi mitundu ya metabol. Ndi chitukuko cha pharmacogenomics, zapezeka kuti ma gelymorphism awo amakhudzana ndi kuchuluka kwa mankhwala enaakebolsm, omwe amakhudza kuchitika, kukula, komanso chithandizo cha matenda ndi zina zambiri.

Phunzirani pamitundu ya mitundu: yerekezerani kusiyana kwa cyp enzyme ntchito yoyamba ipatocyte monga anthu, makoswe, ndi agalu, ndikuyang'ana njira yosinthira.

• Enzyme zoletsa

Cyp enzyme yolumikizidwaenzyme zoletsaAmanena za izi pomwe zina zimalepheretsa ntchito ya cyp450 metabolic, zomwe zimachepetsa mankhwala, komanso kuwunika kwa mankhwala ena akamagwiritsa ntchito, potero ndikuyika ngozi. Malinga ndi njira zosiyanasiyana zosiyanirani, zotsatira za mankhwala osokoneza bongo pa cyp450 michere imatha kugawidwa kuti ikhale yopingasa komanso nthawi yoletsa (TDI). Choletsa kudalira nthawi, chomwe chimadziwikanso kuti choletsa chosasinthika, nthawi zambiri amatanthauza mapangidwe a mankhwala osokoneza bongo komanso enzyme yolumikizirana. Mphamvu yolepheretsa yoletsa pa enzyme siitha nthawi yomweyo atachotsedwa, koma akuwonetsa nthawi - machitidwe - machitidwe a.

• Cyp40 enzyme metabelic Phunziro

Pakadali pano pali njira zitatu zofunika kwambiri zodziwitsira enzyme metabolic pyp450: Njira zoletsa zoletsa, njira yobwezeretserani ya Cyp450 Isoenzyme Njira, ndi Njira Yokonzanso Chidule. Njira yoletsa zoletsayi imatha kugawidwa mu njira yoletsa mankhwala ndi njira yoletsa antibody. Zimaphatikizapo kuyeza ntchito ya ma microsic of Final Microsies pa mankhwala osokoneza bongo omwe ali ndi ma enzyme shuppes kapena ma antibodies osokoneza bongo a chiwindi enzyme metabolic Phenotype. Mwa iwo, njira yoletsa zamankhwala yagwiritsidwa ntchito kwambiri chifukwa cha ntchito yake yosavuta komanso mtengo wotsika.

• Mapeto

Michere ya cyp michere ndi ma enzymes, monga ma enzymes a syzyme a metabolism, oxidation, kuchepetsa) ndi gawo laulemu, pozindikira, komanso kugwiritsa ntchito mwadongosolo mankhwala osokoneza bongo. Subypes monga cyp3a4 ndi cyp2d6, limodzi ndi ma enzyme monga Ugt1a1 ndi UGT2B2b7, pangani network yovutayi. Kusintha kwawo kwa ntchito (monga gene polymorphism ndi mitundu ya mitundu) kumatha kusanthula molondola kudzera mu Hepatocytes wamkulu ndi LC - MS Irtenology, ndikupereka chithandizo chofunikira pakupanga mankhwala.

Kuchulidwa

Zhang, M., Vottschäfer, V. & CM LET Lange, E. (2024). Zotsatira zomwe zingachitike kwa cyp ndi ugt mankhwala - minyewa yopukusira pamatumbo a bongo amawonekera mankhwala. Ndemanga Zapakatikati pa Mankhwala, 56(1), 1 - 30.

A GLASHAS, A., Ramanathan, R., kishnani, N. S. Cytochrome P450 (cyp) ndi udp - glucuronosyltransferase (ugt) ma enzymes: Udindo wa kagayidwe ka mankhwala, polymorphs, ndi chizindikiritso chawo pakugawana mankhwala. Mu Kupita Kwachipatala ndi Kusanthula (Vol. 6, PP. 295 - 336). .