Kushandiswa kweokisijeni kwakawanda kunoreva ATP yakawanda here? Zvidzidzo kubva kutsvakiridzo yemethylene blue

Mitokondriya imwe yakaparadzaniswa iri mukamuri rekuyedzera rine chinopa simba asi risina ADP. Inoshandisa okisijeni zvishoma nezvishoma. Kana ADP yawedzerwa, kushandiswa kweokisijeni kunokwira kakawanda. Kana wamirira kusvikira ADP yapera, kushandiswa kweokisijeni kunodzika zvakare. Chinopa simba hachina kumbochinja. Chakachinja chete kwaiva kudiwa kweATP.

Kutevedzana kudiki uku kunoratidza musiyano wose uri kukurukurwa muchinyorwa chino. Kushandiswa kweokisijeni kunoyera kumhanya kunoita maerekitironi achipfuura nemucheni yekufema achienda kuokisijeni. Kugadzirwa kweATP kunoyera kuti chikamu chakawanda sei chekuyerera ikoko chinochengetwa sesimba rinogona kushandiswa. Zviviri izvi zvine danho repakati rakafanana: gredhiyenti yemaprotoni kumativi maviri emembrane yemukati yemitokondriya. Chinhu chipi nechipi chinoshandura kusimba kwekubatanidzwa kwegredhiyenti nekugadzirwa kweATP chinogona kuita kuti zviyero zviviri izvi zviende kumativi akasiyana. Methylene blue inobatsira kudzidzisa izvi nokuti yakaonekwa ichiita zvose: mune mimwe mienzaniso yakagadzirirwa kuedzwa inowedzera kushandiswa kweokisijeni pamwe chete neATP, uye mune mimwe inowedzera kushandiswa kweokisijeni asi ATP ichiramba yakangofanana kana ichiderera.

Vaverengi vanoda kutanga vanzwisisa mufananidzo wakakura wekupfuudzwa kwemaerekitironi vanogona kutanga nekuverenga kuti methylene blue inotakura sei maerekitironi nemucheni yekufema. Vanoda kunzwisisa mazwi emiedzo yokutanga yeokisijeni vanogona kuverenga kuti zviyero zvokutanga zvekufema zvakaratidza chii chaizvo.

Kufema, ATP, uye gredhiyenti iri pakati pazvo

Maerekitironi anobva kuNADH neFADH2 anopinda mucheni pamakomplekisi I neII, opfuura nomukomplekisi III achienda kucytochrome c, ozopfuura nomukomplekisi IV achienda kuokisijeni. Simba rinobudiswa pamakomplekisi I, III, neIV rinopomba maprotoni kubva mumatrix richiaisa munzvimbo iri pakati pemamembrane. Kuparadzaniswa ikoko kwechaji yemagetsi neasidhi ndiko simba rinosunda maprotoni, uye chikamu charo chemagetsi, chinonzi membrane potential, ndicho chinowanzonyanya kukosha.

ATP synthase inorega maprotoni achiyerera achidzokera mumatrix uye inoshandisa simba rinobudiswa kubatanidza ADP nephosphate kuti zvive ATP. Saka cheni yacho ndeiyi:

kushandiswa kweokisijeni, kwozotevera kupombwa kwemaprotoni, kwozotevera gredhiyenti, kwozotevera kugadzirwa kweATP.

Dambudziko nderekuti maprotoni anogona kudzoka nedzimwe nzira. Kudzoka kupi nokupi kusingapfuuri neATP synthase ndiko kubuda kwemaprotoni. Kubuda uku kunomanikidza cheni kupomba maprotoni mamwe chete zvakare kuti membrane potential irambe yakatsiga, zvichishandisa okisijeni yakawanda pasina kugadzira ATP yakawanda. Kana kubuda uku kwakasimba zvakakwana, kunoparadzanisa kufema nekugadzirwa kweATP: kushandiswa kweokisijeni kunokwira asi ATP ichiramba yakangofanana kana ichiderera, uye simba risina kushandiswa rinobuda sekupisa.

Mamiriro 3, mamiriro 4, uye reshiyo yekudzorwa kwekufema

Mazwi echinyakare anoshandiswa pano anobva pamitokondriya yakaparadzaniswa. Mamiriro 3 kufema kunoitika paine sabstreti pamwe chete neADP: ATP synthase inoderedza gredhiyenti, membrane potential inodzikira, cheni inokurumidza kuidzorera, uye kushandiswa kweokisijeni kunenge kwakakwira nokuti ATP iri kugadzirwa. Mamiriro 4 kufema kunoitika kana ADP yapera: ATP synthase haichashandi, gredhiyenti inokwira, membrane potential yakakwira inodzivisa kumwe kupomba, uye kushandiswa kweokisijeni kunodzika kusvika pachiyero chinodiwa kutsiva maprotoni ari kubuda.

Naizvozvo reshiyo yekudzorwa kwekufema, inova mamiriro 3 akakamurwa nemamiriro 4, inoratidza kusimba kwekubatanidzwa mumuenzaniso wakagadzirirwa kuedzwa. Reshiyo yakakwira inoreva kuti ADP inodzora kufema zvakasimba. Reshiyo iri kuderera apo mamiriro 4 ari kukwira inoreva kuti kubuda kwemaprotoni kuri kuwedzera kuva ndiko kunotonga. Iyi ndiyo nzira yokunzwisisa nayo migumisiro yemethylene blue iri pasi apa.

Pane mufananidzo mumwe wokufunga wakakodzera kuchengetwa mupfungwa. Membrane potential yakakwira inononotsa cheni. Kuderera kwepotential iyi kunoikurumidzisa. Cheni inopindura kuoma kwaita kupomba, kwete zvakananga kuti ATP iri kugadzirwa here.

Apo zviyero zvinokwira pamwe chete

Muenzaniso wakajeka zvikuru wekubatana unobva kumitokondriya yakaparadzaniswa yeuropi hweguinea pig ine makomplekisi ekufema akavharwa. Pamethylene blue iri pakati pe100 nanomolar ne1 micromolar, kushandiswa kweokisijeni pakuzorora kwakakwira paishandiswa glutamate pamwe chete nemalate, succinate, kana glycerophosphate sezvinopa simba, asi kufema kwakakurudzirwa neADP hakuna kuchinja. Mumitokondriya yakakanganiswa nechepfu pakomplekisi I kana komplekisi III, dhayi iyi yakawedzera kugadzirwa kweATP zvishoma, ikadzorera membrane potential, uye ikavandudza kutorwa kwecalcium. Nzira yakafungidzirwa inzira yokudimbudzira: dhayi inogamuchira maerekitironi asati asvika panzvimbo yakavharwa, yoapa kucytochrome c, ichipfuura nepamwe pasina kushandisa komplekisi yakakuvadzwa.

Muenzaniso wechipiri wekubatana unoshandisa imwe nzira yakasiyana zvachose yokugadzira ATP. Mumitokondriya yakaparadzaniswa yeuropi ine ATP synthase yakadziviswa kushanda, methylene blue yakaramba ichikurudzira kufema pasabstreti yose yakaedzwa. Asi kugadzirwa kweATP kwakakwira chete paalpha ketoglutarate neglutamate, masabstreti maviri anogadzira succinyl CoA. Sezvo oligomycin yaivharira ATP synthase, ATP yakawedzera yakabva pakuiswa kwephosphate pasabstreti kunoitwa nesuccinyl CoA ligase mudenderedzwa recitric acid, kwete pakugadzirwa kweATP kuburikidza neoxidative phosphorylation. Dhayi iyi yakadzorerawo membrane potential apo komplekisi I neATP synthase zvakadziviswa kushanda pamwe chete. Pano kushandiswa kweokisijeni neATP zvakafamba pamwe chete, asi chete apo sabstreti yaibvumira nzira yechipiri yokugadzira ATP. Pasuccinate kana malate, kufema kwakakwira pasina ATP yakawedzera. Dhayi imwe chete, kamuri rimwe chete, chinopa simba chakasiyana, mhinduro yakasiyana.

Apo zviyero zvinoparadzana

Mienzaniso inoratidza kuparadzana yakabudiswawo uye inodzidzisawo zvakafanana. Mutsvakiridzo ya1997 yemitokondriya yakaparadzaniswa yechiropa chemakonzo, methylene blue yakakurumidzisa kufema kwemamiriro 4 mumitokondriya yaiva nekubatana kwakasimba uye yaishandisa succinate pakufema, zvichiita kuti reshiyo yekudzorwa kwekufema iderere. Izvi zvakaonekwa kubva pa0.5 micromolar uye zvakanga zvakasimba pa5 micromolar, chiyero chiri pedyo nechiri muplasma pashure pekupinzwa kwe100 milligram mutsinga kamwe chete. Pa5 micromolar mitokondriya yakazvimbawo, kunyange zvazvo kukanganisika kwekubatanidzwa kwakatanga kuonekwa pazviyero zvakaderera. Izvi zvinotsigira pfungwa yokuti kubuda kwemaprotoni kwakatangira kukuvadzwa kwechimiro, kwete kuti kwakakonzerwa nako. Mumitokondriya yakanga yatove nekuparadzana kwekufema nekugadzirwa kweATP, dhayi yakakurudzira kufema nenzira yaienderana nechiyero chayo uye yaigona kusvika pamuganhu. Kushandiswa kweokisijeni kwakakwira mumienzaniso yose miviri yakagadzirirwa kuedzwa. Kugadzirwa kweATP paokisijeni yakashandiswa hakuna kukwira. Uku ndiko kuparadzaniswa kwekufema nekugadzirwa kweATP pamwe chete nekutakurwa kwemaerekitironi zvinotsanangurwa mumabhuku, zvichiitwa nemorekuru rimwe chete.

Kuparadzana kunonyanya kushamisa kunobva muretina. Mumbeva dzine kushomeka kweAIF nemaseru anogamuchira chiedza akaiswa rotenone, methylene blue yakachengetedza ukobvu hweretina, zviratidzi zvinoratidza maseru anogamuchira chiedza, uye chimiro chemitokondriya. Yakaderedzawo reshiyo yeNADH kuNAD uye ikadzikisa kushanda kwenzira dzokupindura kushushikana kweseru, kusanganisira kupindura kumapuroteni asina kupetwa zvakanaka uye mitophagy. Yakaita izvi isina kugadzirisa kushomeka kweATP. Kudzivirirwa pasina kudzorerwa kwesimba kunoreva kuti rubatsiro rwakabva pakudzikamiswa kwemaitiro eredox nekuchengetedzwa kwechimiro chemitokondriya, kwete paATP yakawedzera. Munhu anofananidza kupona kwetishu nekudzorerwa kwekugadzirwa kwesimba anganzwisisa muedzo iwoyo zvisizvo zvachose.

Tsvakiridzo yemitokondriya yeuropi inowedzera rutivi rwemutengo pamufananidzo mumwe chete uyu. Zviyero zvakaderera zvimwe chete zvakavandudza maitiro esimba mumasero zvakawedzerawo kugadzirwa kwehydrogen peroxide mumamiriro ose akaedzwa uye zvakanonotsa kubviswa kwayo. Izvi zvakayerwa nemuedzo weAmplex wakagadziriswa kuti uyere zvakarurama, kwete nedhayi isingatarisi chinhu chimwe chete. ATP yakawanda nezvinhu zvinokonzera oxidation zvakawanda zvakauya pamwe chete.

Rondedzero yokubatsira pakuverenga

Mibvunzo mina inoparadzanisa mugumisiro une kubatana kwekufema nekugadzirwa kweATP kubva kune usina kubatana ikoko.

Wokutanga, chii chaizvo chakayerwa. Kushandiswa kweokisijeni chete hakugoni kuratidza ATP. Kugadzirwa kweATP, membrane potential, uye reshiyo yekudzorwa kwekufema chimwe nechimwe zvinowedzera chikamu chemashoko chisingaonekwi neerekiturodhi yeokisijeni. Gwaro rokuverenga zvinotaurwa netsvakiridzo yemethylene blue rinotsanangura zvakadzama nzira iyi yokutarisisa zvakayerwa.

Wechipiri, ndeipi sabstreti yakapa mitokondriya simba. Mugumisiro wesuccinyl CoA unoratidza kuti kusarudzwa kwechinopa simba kunogona kusarudza kuti kufema kwakawedzera kungatombova ATP yakawedzera here.

Wechitatu, chiyero chipi chakashandiswa. Methylene blue iri kubva pananomolar kusvika pamicromolar yakaderera mumitokondriya yeuropi yakavandudza maitiro esimba zvishoma, asi ichiwedzerawo zvinhu zvinokonzera oxidation; hafu yemicromolar zvichikwira mumitokondriya yechiropa zvakaderedza kubatanidzwa; 5 micromolar yakawedzerawo kuzvimba. Chiyero chikamu chemaitiro acho, kwete mashoko asina kunyanya kukosha.

Wechina, muenzaniso upi wakabudisa mugumisiro wacho. Mitokondriya yakaparadzaniswa inoratidza mabatanirwo emukati, asi maseru nematishu akakwana anowedzera kutakurwa kwezvinhu, kushandurwa kwemethylene blue kuita chimiro chisina ruvara kuburikidza nereduction, uye dzimwe nzira dzinokwikwidzana mukugamuchira maerekitironi. Basa remurabhoritari rokuedza huwandu hunoiswa, kusanganisira kuti chiyero nemaitiro emuedzo zvinoumba sei zvinokonzerwa nemethylene blue, ndiro zambuko pakati pezviverengo zvemukamuri rekuyedzera nechinhu chipi nechipi chinotaurwa nezvomunhu.

Kushandiswa kweokisijeni kunoratidza kuyerera kwemaerekitironi. ATP inoratidza kuti chikamu chakawanda sei chekuyerera ikoko chakachengetwa. Methylene blue inogona kushandura chimwe nechimwe chazvo, uye miedzo iri pamusoro inoratidza misanganiswa mina yose inotevera: zvose zvinokwira, kufema kunokwira chete apo sabstreti inobvumira, kufema kunokwira asi kubatanidzwa kuchiderera, uye tishu inochengetedzwa asi ATP ichiramba yakangofanana. Nhamba inoratidzwa neerekiturodhi yeokisijeni ndiyo mavambo ekududzira, kwete magumo ako.