Ts'ebeliso ea Cytochrome P450 (Cyp450) le UDP - Litsebi tsa Serusp tse mabapi le Mebilic Phenotype le Enzyme thibelo

Mantsoe a Bohlokoa: Sekhachane - Litsebi tsa lithethefatsi (DDI), Cytochrome P450 (Cyp350 Enzubulsylp. Cyp3a4 / 5, cyp2e1, Ugt1a1, Ugt1a4, Ugt1a10, Ugt1Bb, Ugt2b15, Ugt2B17.

• Ts'ehetso ea Iphase

Tlhokomeliso: Liezymes tsa cyp hangata li sebelisoa leSistimi ea Nadph ea Nadph/ NadphMmePbs
Li-enzymes tse mpe hangata li sebelisoa leSistimi ea Uggle pbs.

Metabolism e bapala karolo ea bohlokoa molemong oa lithethefatsi, a amang ho ba le tšebeliso ea tsona 'meleng le ka hona a susumetsang sebaka se hlahelletseng le ho ama seqobo se itseng. Sena se etsahala haholo ka sebete, empa se ka boela se hlaha li-orgeas tse sa hlakang. Lithuto tsa morao-rao li senotse boteng le bohlokoa ba enzymes tsa lithethefatsi (dme) bokong.Cytochrome p450 enzyme (cyP)MmeUdp - Glusubusyltransferanse (Uthet) Hape ke barupeluoa ba bohlokoa lithong tsa lithethefatsi tse sebelisoang ka har'a sistimi ea methapo e bohareng ea methapo ea methapo ea methapo ea methapo (CNS).

• Cytochrome p450 (cyP)

Cytochrome P450 e lula e le mekhahlelo ea metabolism (oxidation, phokotso, hydrolysis), e ikarabellang bakeng sa metabolism ea lithethefatsi. Metabolism ea lithethefatsi (50% ea lithethefatsi (50%) le li-metabolism) le cyp2d6 (20% lithethefatsi). Selekane se fetoloa lipelaelo tsa lipophilic e le metaboselite ea polar Polar, e khothatsang.

Makhethe tsa mantlha ke li-ipatocytes tse ikhethileng ka ho toba ea batho ba ratang ho sebelisa tšebetso ea bona ea ho boloka metabolis e sa sebetseng hantle. Mohlala oa mantlha oa li-Ipatocytes ke mohlala oa tlhahlobo o amoheloang ka ho fetisisa oa ho inehela indasteri indasteri, academia le mekhatlo e phatlalatsang. Joaloka sistimi ea selefouno, lefu la setjhacyte ea batho le entsoe ka li-incleater tsa nyutlelie, li-inshitomitors, enzyme e khona ho sebelisa lithethefatsi le metabosotes tsa bona.

• Udp - Glusubusyltransferanse (Uthet)

UDP - Glusubossylltransferasferasesferasesferasesferasesferases ea mantlha e sebelisang li-glucunick ecid ea acid ea gluccunind e nang le lintho tse phahameng tsa Pluzens, ho khothaletsa tumello ea eona. Motho o ajoa haholo o ajoa haholo 'me o hlahisoa ka lisele tse kang sebete, mala, a liphio, le mats'oafo le matšoafo. Sebete ke setho sa mantlha 'meleng oa motho o tsoileng matsoho a khethollo ea acid ea asiti,' me Liboto tse ngata tse mpe li hlahisoa ka sebete. Ugt1a7, Ugt1a8, Ugt1a10, 'me Ugt2a10 li ajoa li-seshune tse feteletseng,' me haholo-holo lisele tse tsoang maemong a feteletseng li amana haholo le monyaluoa le ho nyalisoa.

• Likopo tsa senotlolo ntoeng ea lithethefatsi

Ka har'a mofuta oa vitro: li-enzymes tse joalo tse joalo ka li-microsocytes tsa li-microker tsa maoatle A sebelisa lisele tsa mofuta o hlophisitsoeng ho bolela lintho tse fapa-fapaneng tsa metabolical.

Sehlekehleke sa lithethefatsi - Tšebelisano ea lithethefatsi (DDI)Boithuto: Boitšoaro ba Boitšoaro ba Cyp Ho bona Hore na Lithethefatsi (tse kang CyzyMa4, cy3A4, cy - e bolelang esale pele. TYFATSIGY UKHIPY Life SHITHIPS ho lekola litlamorao tsa lithethefatsi mosebetsing o mongata. Ho lemoha phello ea lithethefatsi ho cyP / Ust ka tlhahlobo ea mantlha ea Hepatocylis.

Nts'etsopele ea mekhoa ea thuto ea tlhaho: Boikathabe ba Popa le bosholu ba nts'etsopele ea lithethefatsi tsa binalytical le pharmaCokitic (DPPK). Sebelisa metrina ea likokoana-hloko e nang le metabolite e nang le cyp / e joalo ka plasma) bakeng sa pherekano ea margen phello, mekhoa ea MS / ea ho ntlafatsa litlamorao tsa ion

Patlisiso ea likokoana-hloko tsa lefutso: Ugt1a1 le mefuta e meng e nang le polelo ea mafu a ma-enzyme ke mefuta ea bohlokoa mehleng ea batho. Ka nts'etsopele ea litlhare tsa litlhare, ho fumanoe hore poli ea poone ea lefu la liphatsa tsa lefutso e amana le metabolism ea metabolism, eo ka eona e amang mafu, nts'etsopele le likarolo tse ngata.

Ho ithuta ka mefuta ena: Bapisa liphapang: Ho bapisa lintho tsa enzy Enzyme tsa Mathomo, litopo le lintja le ho ntlafatsa ts'ebetso ea bongaka.

• Thibelo ea enzyme

Cyp enzyme e kopantsoengthibelo ea enzymeE bua ka ketsahalo eo metsoako e 'ngoe e ka sitisang tšebetsong ea li-cyp450, litekanyetso tse fokotsehileng, ka tsela e ngata li tsamaisa kotsi ea polokeho. Ho latela mekhoa e fapaneng ea thibelo, phello ea litlhare tsa lithethefatsi ho cypymes e kenang tsa cyp350 e ka aroloa hore e be thibelo e matlafatsang le ho its'etleha. Ho bakoa ke nako ho ne ho tsebahala ha lithethefatsi, e tsejoa hape e le thibelo e ke keng ea fetoloa lipakeng tsa sethethefatsi sa mokhethoa, e fella ka bonngoe ba mokhethoa, e bakang enzyme enzyme e ke keng ea fetoloa. Tšusumetso ea thibelo ea enzutor e sa nyamele hang-hang ka mor'a hore Inhibitor e tlosoe, empa e bontša nako - litšobotsi tse itšetlehileng ka tsona.

• Cyp450 enzyme Metabolic Pheonotyping Ithute

Hajoale, ho na le mekhoa e meraro e ka sehloohong ea ho tsebahatsa phepelo ea enzzy ea enzzlic ea enzyme, mokhoa oa ho khetha li-cyp450. Mokhoa oa ho khetha joala o ka aroloa ka mokhoa oa thibelo ea lik'hemik'hale le mokhoa oa thibelo ea thibelo. Ho kenyelletsa ho lekanya tšebetso ea metabolic ea Li-Microsomes tsa Batho ba Seng Majene ea Lithethefatsi phenotype. Har'a bona, mokhoa oa li-Niltics o sebelisoa haholo ka lebaka la ts'ebetso ea eona e bonolo le litšenyehelo tse tlase.

• Sephetho

Li-enzzmes tsa corzle le li-enzyme tsa mantlha, ho laola karolo ea lithethefatsi, ho ama ts'ebetso ea lithethefatsi, ho ama maqhubu le ho sebelisa lithethefatsi hantle le ho sebelisa lithethefatsi. Li-Stucopes tse kang cyp3a4 le cyp2d6, hammoho le enzymes tse kang Ugt1a1 le Ugt2b7, li etsa netweke e rarahaneng ea metabolic. Phapang ea bona ea tšebetso (joalo ka mefuta ea liphatsa tsa lefutso le mefuta ea liphallelo) e ka hlahlojoa ka nepo mekhoa ea mantlha ea li-Hepatocytes.

Resort

Zhang, M., Rottschäfer, V., & CM La La La La Lamare, E. (2024). Kameho e ka bang teng ea sethethefatsi le sethethefatsi - metabolising e tsoang ho phapanyetsano ea kelello sa boko. Litlhahlobo tsa lithethefatsi tsa Metabolism, 56(1), 1 - 30.

Ghosal, A., ramanathan, R., Kishnani, K., Chowdhury, S., & Alton, K. B. (2005). Cytochrome P450 (Cyp) le UDP - GlusulanosylltransfenSfenSfensferase (UGET) Ho Tsoelo-pele ho Phatlalatso ea Pharmaceutical le Biomedical (Mohala. 6, maq. 295 - 336). Elfvier.