Ubururu bwa metilene na NAD+/NADH: gusobanukirwa iringaniza rya redox mu ngirabuzimafatizo

Raporo zivuga ku bururu bwa metilene na NAD+ zikunda kuvanga ibivugwa bitatu bitandukanye zikabigira kimwe. Icya mbere ni uko igipimo cya NAD+ kuri NADH cyerekeje ku miterere yatakaje elegitoroni. Icya kabiri ni uko ingirabuzimafatizo ifite ingano yose ya NAD irushijeho kuba nini. Icya gatatu ni uko umusaruro w'ingufu wagarutse. Ibi byumvikana nk'inkuru imwe yo gusubiza imikorere y'ihinduramatwara ku murongo. Mu igerageza, akenshi ibyo bitatu ntibijyana, kandi ibisubizo bishishikaje ni bya bindi bigaragaza ko bitandukanye.

Urwo rujijo rurumvikana kuko ibyo bipimo bitatu bikoresha amagambo amwe. NAD+ yakira elegitoroni mu bikorwa by'ihinduramatwara igahinduka NADH; hanyuma mitokondiriya zigakuraho elegitoroni kuri NADH zikayisubiza muri NAD+ kuri kompleks I, zigakoresha ingufu zirekuwe mu gukora ATP. Ibisobanuro birambuye by'urwo rugendo rwa elegitoroni biri mu nyandiko isobanura itwarwa rya elegitoroni muri mitokondiriya, naho ibyerekeye ingufu biri mu ATP n'ihinduramatwara ry'ingufu. Ariko igipimo n'ingano yose ni ibintu bitandukanye. Igipimo kigaragaza uko molekile zisanzwe zitwara elegitoroni zigabanyije hagati y'izizifite n'izitazifite. Ingano yose yo igaragaza umubare wa molekile zitwara elegitoroni zihari zose. Igipimo cyiza kurushaho, ingano yose itahindutse, gisobanura ko izisanzwe zongeye kugabanywa, atari uko hakozwe izindi.

Ibice bibiri, ibipimo byerekana imiterere bibiri

Hari irindi tandukaniro ritera gusoma ibisubizo nabi bitagaragara. NAD iri muri sitozoli n'iri muri mitokondiriya ahanini bitandukanywa n'agahu k'imbere ka mitokondiriya, bityo buri gice gishobora kugira NAD yiganjemo iyatakaje cyangwa iyakiriye elegitoroni mu buryo bwacyo. Umubare umwe ugaragaza ingirabuzimafatizo yose uhisha iryo tandukaniro.

Ubushakashatsi ku mwijima bwatumye iryo tandukaniro ry'ibice ripimika. Iringaniza hagati ya lactate na pyruvate rigaragaza igipimo cya NAD+ kuri NADH muri sitozoli, kuko lactate dehydrogenase ihuza izo molekile ebyiri n'ubwo bwoko bubiri bwa NAD. Iringaniza hagati ya 3-hydroxybutyrate na acetoacetate rigaragaza igipimo cyo muri mitokondiriya binyuze mu ihuzwa risa n'iryo. Iyo izo mpande zombi zipimwe mu rugingo rwakonjeshejwe ako kanya hakoreshejwe igikoresho kirufata, nk'uko byakozwe mu bushakashatsi ku mbeba zagaburiwe ethanol igihe kirekire, haboneka ibipimo bibiri bya redox byo mu mwijima umwe, kandi ikinyabutabire gishobora guhindura kimwe kurusha ikindi.

Ubururu bwa metilene bukora muri ubu buryo nk'ubutwara elegitoroni aho kuba isoko y'ingufu. Bwakira elegitoroni zivuye kuri NADH hafi ya kompleks I, bukajya mu miterere yakiriye elegitoroni, hanyuma bukazigeza ku bitwara elegitoroni biri imbere mu nzira, nka cytochrome c. Igisubizo rusange ni uko NADH itakaza elegitoroni zitanyuze mu nzira isanzwe yose. Ubwo buryo bwo gukora busobanura impamvu bushishikaje n'aho ubushobozi bwabwo bugarukira: bushobora kugabanya kwirundanya guterwa n'iyakira rya elegitoroni rikabije, ariko ntibusana kompleks yangiritse cyangwa ngo bukore molekile nshya za NAD.

Ubushakashatsi butanu, ishusho imwe y'ibisubizo bitajyana

Imbonerahamwe ikurikira itondeka ubushakashatsi butanu hakurikijwe urugingo, igipimo cya redox, igipimo cy'ingufu n'icyagarutse koko. Soma inkingi ebyiri za nyuma uzifatanyije. Uko gufatanya ni ko ntego y'iyi nyandiko.

Aho gukosora redox bitatumye urugingo rusubirana

Ubushakashatsi bwa kera kurusha ubundi muri iri tsinda buracyatanga umuburo usobanutse kurusha indi. Imbeba zagaburiwe ethanol itanga 36 ku ijana by'ingufu zagize ibipimo bya NAD+/NADH byagabanutse muri sitozoli no muri mitokondiriya, bipimwa hifashishijwe izo mpande zombi zerekana imiterere. Ubururu bwa metilene buri mu ndyo, ku kigero cya hafi 42 mg kuri kg ku munsi, bwakumiriye ahanini ayo mahinduka. Nyamara, ku gihe cya nyuma cyo gupima, triacylglycerol yo mu mwijima yari yiyongereye ikagera hafi ku nshuro eshatu, haba hari irangi cyangwa ridahari, kandi isuzuma ry'ingingo munsi ya mikorosikopi ryagaragaje ibinure bimwe hafi y'imitsi yo hagati mu duce tw'umwijima. Abanditsi bavuze mu buryo butaziguye umwanzuro utari woroshye kwakira: ihinduka rya redox rijyana no gutakaza elegitoroni kwa ethanol si ryo ryonyine ritera umwijima urimo ibinure byinshi. Umusomyi wafata igipimo cyakosowe nk'urugingo rwakosowe yaba asobanuye nabi ubu bushakashatsi. Uburyo bwose bwakoreshejwe, harimo amatsinda yo kugereranya yagaburiwe ingano zingana n'ibipimo byafashwe saa sita z'ijoro igihe ubusinzi bwari bukabije cyane, busobanurwa mu bushakashatsi ku mwijima na ethanol.

Gereranya ibyo n'ubushakashatsi ku mwijima bwakoresheje indyo irimo ibinure byinshi, aho ihinduka ry'igipimo risa n'iryo ryajyanye no gusubirana nyakuri kw'urugingo. Mu ngirabuzimafatizo z'umwijima no mu mwijima w'imbeba nyuma yo guhabwa ubururu bwa metilene mu kanwa, bwazamuye igipimo cya NAD+/NADH, kandi uruhererekane rw'ubutumwa bwarakurikiwe intambwe ku yindi: SIRT1 yariyongereye, PGC-1alpha ikurwaho amatsinda ya acetyl, ibimenyetso byo kuremwa kwa mitokondiriya n'ikoreshwa rya ogisijeni biriyongera, hanyuma AMPK, CPT-1 na PPARalpha birakora, kandi bigaragazwa ko ikangurwa rya AMPK rishingiye kuri SIRT1. Imbeba zagaburiwe indyo irimo ibinure byinshi zarundanyije ibinure bike mu mwijima. Ibisobanuro byatanzwe ni uko ihinduka rya redox hano ryafunguye inzira igenga imikorere ya jene, aho kuba gusa gusubiza ubutabire mu iringaniza, nk'uko bisobanurwa mu bushakashatsi ku mwijima, SIRT1 na AMPK. Ubwoko bw'ibipimo ni bumwe n'ubwo mu bushakashatsi bwa ethanol, ariko umwanzuro ku rugingo uratandukanye. Itandukaniro riri mu nzira zikurikira iryo hinduka, si mu gipimo cyonyine.

Umutima na retine: sirtuine, kongerwa kw'amatsinda ya acetyl no gusubirana ATP itagarutse

Ubushakashatsi ku mutima urwaye diyabete buhuza ihinduka rya redox no kongerwa kw'amatsinda ya acetyl kuri poroteyine binyuze muri sirtuine itandukanye. Mitokondiriya zo mu ngirabuzimafatizo zirwaye diyabete zifite amatsinda ya acetyl menshi kuri lysine iri kuri anzime z'ihinduramatwara, bikajyana no kutabasha guhinduranya neza ibinyabutabire bitanga ingufu. Ubururu bwa metilene ku kigero cya 10 mg kuri kg ku munsi bworohereje itakaza rya elegitoroni rya NADH mu buryo bwagendaga buhinduka hakurikijwe ingano yakoreshejwe kuva kuri 6 kugeza kuri 18 micromolar muri mitokondiriya zatandukanyijwe n'ingirabuzimafatizo. Bwongereye imikorere ya SIRT3 kandi bugabanya kongerwa kw'amatsinda ya acetyl ku rugero rwagutse; ingano z'ibyumba by'umutima n'umugabane w'amaraso usohorwa n'umutima na byo byarushijeho kuba byiza, nubwo ikibazo cy'ibanze cya kompleks I cyagumyeho. Inyandiko isobanura neza uko ingano yakoreshejwe ikora mu bundi bushakashatsi: ibipimo bito bishyigikira uruhare rwo gutwara elegitoroni ziva ku bintu bizifite, mu gihe ibinini bishobora kohereza elegitoroni mu zindi nzira zidatanga umusaruro. Bityo ingaruka zishingira ku ihame rya hormesis, aho ingano nto n'inini zishobora kugira ingaruka zitandukanye, aho kugenda ziyongera mu cyerekezo kimwe. Isesengura rya poroteyine n'ibipimo by'umutima biri mu bushakashatsi ku kongerwa kw'amatsinda ya acetyl mu mutima urwaye diyabete. Ibisobanuro by'umunaniro uterwa na okisidasiyo biri inyuma y'ibi biri mu ngingo yerekeye umunaniro uterwa na okisidasiyo no kugenzura ROS.

Ubushakashatsi kuri retine bugaragaza iryo tandukaniro ku rugero rukomeye kurushaho. Mu mbeba za Harlequin zibura AIF, bikagira inenge mu guteranya kompleks I, ubururu bwa metilene bwabungabunze umubyimba wa retine, ibice byo hanze by'ingirabuzimafatizo zakira urumuri, n'ibimenyetso by'ingirabuzimafatizo zimeze nk'uduti, izimeze nk'udusongero, iza Muller n'iza gangiliyoni. Mu ngirabuzimafatizo za 661W zakira urumuri zakorewe rotenone, irangi ryasubije igipimo cya NADH kuri NAD+ ku rwego rusanzwe kandi rigabanya ibinyabutabire bya ogisijeni bikora cyane ku kigero cya 15 micromolar. Nyamara ATP yagumye hasi ku bipimo byatumaga ingirabuzimafatizo zikomeza kubaho. Imiterere no kubaho byarabungabunzwe hatabayeho kugarura ingufu, bijyana no gutuza kw'igisubizo cya mitokondiriya kuri poroteyine zitazingiye neza no kugabanuka kwa mitofaji, ari ko gusenya mitokondiriya mu ngirabuzimafatizo. Icyo gisubizo gituma irangi rifatwa nk'irigabanya umunaniro uterwa n'iyakira rya elegitoroni rikabije n'uterwa na okisidasiyo, aho kuba irigarura ingufu, nk'uko byanditswe mu bushakashatsi ku kurinda ingirabuzimafatizo zakira urumuri muri retine.

Umutsi uhuza inyama n'igufwa: igerageza aho ubutabire bwahindutse ariko urugingo ntirusubirane

Ubushakashatsi ku mutsi wa Achilles burimo izo shusho zombi mu nyandiko imwe, kandi bukwiriye gusomwa witonze. Isesengura rirambuye rya buri gice riri mu isesengura ryo mu 2026 ku burwayi bw'umutsi wa Achilles. Umutsi urwaye wagaragaje kugabanuka kwa NAD+, igipimo gito cya NAD+ kuri NADH, ibimenyetso bike bya kompleks I, ATP nke na kolajeni idatunganye. Ubururu bwa metilene bwagaruye imimerere y'ubutabire bwa NAD na ATP, kandi butuma ibimenyetso bya matrikisi birushaho kuba byiza mu byitegererezo by'imbeba, uduce twakuwe ku bantu n'ingirabuzimafatizo.

Hakurikiyeho uburyo bubiri bwo guhungabanya imikorere. Igihe rotenone yabuzaga kompleks I gukora, irangi ryakomeje kurinda imimerere y'ubutabire bwa NAD+ n'ibipimo bifitanye isano na ATP, ariko ntiryashoboye kugabanya ubwinshi bw'ibintu bitera okisidasiyo, kugarura iringaniza rya kolajeni cyangwa kubungabunga ubushobozi bwo kubaho. Igihe imikorere ya AIF yagabanywaga, aho ibikoresho bya kompleks I byari byarubatswe bidahagije aho kuba byarabujijwe gukora n'ikinyabutabire, irangi ryatumye ibintu byinshi bisubirana: iringaniza rya NAD, umunaniro uterwa na okisidasiyo, itandukaniro ry'amashanyarazi hagati y'impande z'agahu n'ibimenyetso bya kolajeni. Isomo rirasobanutse. Igipimo cya NAD cyiza kurushaho gishobora kubungabungwa n'igihe kompleks I yabujijwe gukora, ariko gusubirana kw'urugingo muri ibi byitegererezo kwashingiraga ku nzira ya kompleks I ishoboye gukora. Muri iyi nkuru, guhinduka kw'igipimo ni ngombwa ariko ntiguhagije, ingingo isobanurwa birambuye mu bushakashatsi kuri redox mu mutsi uhuza inyama n'igufwa.

Uko wasoma ubutaha ibivugwa kuri redox

Ibibazo bitatu bifasha kwirinda gusoma nabi ibisubizo byinshi. Icya mbere, baza igice igipimo kibarizwamo n'impande ebyiri z'ibinyabutabire zakoreshejwe mu kukigaragaza. Igisubizo cya lactate kuri pyruvate muri sitozoli nta cyo kivuga mu buryo butaziguye kuri matrikisi ya mitokondiriya. Icya kabiri, baza niba inyandiko ivuga ihinduka ry'igipimo, ingano yose yiyongereye cyangwa kugaruka kwa ATP, kandi ufate buri kimwe nk'igisubizo cyihariye. Icya gatatu, baza icyakomeje kutagenda neza: ibinure bitagabanutse, inenge ya kompleks I itakosowe cyangwa ibura rya ATP ritakosowe byose bigaragara muri izi nyandiko hamwe no kurushaho kuba byiza kwa redox nyakuri.

Nta na kimwe muri ibi ari amabwiriza y'ingano yo gufata. Ubushakashatsi bwose uko ari butanu bwakorewe ku nyamaswa, ingirabuzimafatizo cyangwa ibyitegererezo by'ingingo, bukoresha ibintu byangiza byagenzurwaga: indyo z'amazi zirimo ethanol, diyabete yatewe na streptozotocin, inenge za kompleks I zikomoka kuri jene, rotenone, peroxide na collagenase. Ibipimo by'ubwinshi bw'ikinyabutabire mu bikoresho by'igerageza ntibihinduka ingano yo gufata mu kanwa ubirebye gusa, kandi nta muntu muri izi nyandiko wafashe ubururu bwa metilene agamije kuringaniza redox. Ingingo ihuza imikorere y'imiti kuri redox n'ingano zayo irafunganye kandi ni ingirakamaro kurusha amabwiriza ayo ari yo yose: ubururu bwa metilene butuma NADH itakaza elegitoroni bugahindura igipimo cyapimwe; mu ngingo zimwe, sirtuine zihindura iryo hinduka mo gukuraho amatsinda ya acetyl no kongera kugena imikorere y'ihinduramatwara; kandi kuba urugingo rukurikira iryo hinduka bishingira ku bikoresho by'imikorere irangi ridashobora gusimbura.