Ubururu bwa metilene ugereranyije n'uburyo bwa NAD+: imikorere, ibimenyetso, n'ibivugwa ku kubihuza

Ubururu bwa metilene n'inyunganiramirire zigurishwa nk'izongera NAD+ byombi bisobanurwa hifashishijwe amagambo mitokondiriya n'ingufu z'uturemangingo. Nta na kimwe muri ibyo bisobanuro kikubwira icyo igicuruzwa gikora koko.

Ubu buryo bubiri bukora ku bipimo bitandukanye. Bumwe bugerageza guhindura ingano ya NAD+ iri mu turemangingo twawe. Ubundi buhindura igipimo kiri hagati y'imiterere yayo ibiri. Izo si inzira ebyiri zigana ahantu hamwe.

Imibare ibiri ikunze kwitiranywa

NAD+ ni koenzime. Yakira elekitoroni ebyiri, ziri mu buryo bwa iyoni ya hydride, igahinduka NADH. Iyo NADH ihaye izo elekitoroni ibindi biyakira, yongera kuba NAD+. Uturemangingo dukoresha uru ruziga buri gihe: ni ko ingufu zivanwa mu biribwa zigera ku mikorere ya poroteyine zikora ATP.

Kubera ko NAD+ na NADH ari imiterere ibiri ya molekile imwe, akaremangingo gafite ingano ebyiri zitandukanye zikwiye gukurikiranwa. Iya mbere ni igiteranyo cyose: ingano ya NAD+ na NADH byose hamwe. Iya kabiri ni igipimo kiri hagati yabyo, gisobanura uko ibitwara elekitoroni byuzuye muri ako kanya.

Ikigega cy'amazi gituma iri tandukaniro ryumvikana neza. Ingano y'amazi ari inyuma y'urugomero ni cyo giteranyo. Uko amazi abitswe hejuru y'urugomero agereranywa n'ayasohowe akajya hepfo ni cyo gipimo. Ushobora kuzamura icyo gipimo utongereyeho litiro n'imwe, ufunguye irembo ry'amazi. Ibyo si ikigereranyo gusa cy'icyo ubururu bwa metilene bukora. Byegereye ibisobanuro by'uko bukora koko.

Uburyo bwo kongera ibikoresho fatizo

Inyunganiramirire z'ibibanziriza NAD+, zirimo nicotinamide riboside, nicotinamide mononucleotide, na nicotinamide, ni ibikoresho fatizo. Uturemangingo twubaka NAD+ binyuze mu nzira yo kongera gukoresha ibikoresho yitwa inzira yo kugarura, kandi ibibanziriza NAD+ biyinjiramo. Intego ni ukongera igiteranyo cyose.

Mu nyamaswa, ibi byamaze kugaragazwa neza: mu buryo bwinshi bukoreshwa mu bushakashatsi, NAD+ yo mu ngingo igabanuka uko imyaka yiyongera no mu ndwara z'imikorere y'umubiri ihindura intungamubiri, kandi gutanga ibiyibanziriza bikunze kuyongera. Mu bantu, ibimenyetso biragabanuka. Igerageza ryo mu bantu ryerekana koko ko ibi binyabutabire byongera ingano ya NAD+ ipimwa mu maraso. Icyo bitaragaragaza ni ugutera imbere guhoraho mu bipimo by'ubuzima, ni ukuvuga ibintu umuntu yabona cyangwa igerageza rigamije gupima.

"Ingano ya NAD+ yariyongereye" bipima ikintu kiri imbere mu mubiri. Si umwanzuro werekeye uko umuntu yumvise ameze, uko yagendaga, cyangwa uko yagaruye imbaraga.

Icyo ubururu bwa metilene bukora aho kubikora

Ubururu bwa metilene si ikibanziriza NAD+. Ni irangi rigira uruhare mu kwamburwa no kwakira elekitoroni, rimaze imyaka irenga ijana rikoreshwa mu buvuzi, kandi imikoreshereze yaryo yemewe ni mike ugereranyije n'ikirimo gukorwaho ubushakashatsi.

Imbere mu karemangingo, enzime zishingiye kuri flavin zituma ryakira elekitoroni rigahinduka leucomethylene blue, imiterere itagira ibara, hanyuma rikongera kwamburwa elekitoroni. Elekitoroni zari kunyura muri komplegisi I, igice cya mbere cy'uruhererekane rw'ubuhumekero bw'akaremangingo zishobora ahubwo kuvanwa muri NADH zinyuze mu bururu bwa metilene. NADH ihinduka NAD+.

Igipimo kirazamuka. Igiteranyo cyose ntikiyongera.

Ubushakashatsi bwakorewe ku mbeba ku mutima urwaye diyabete bwapimye ibi mu buryo butaziguye muri mitokondiriya zavanywe mu mutima. Kongeramo ubururu bwa metilene ku ngano iri hagati ya 6 na 18 micromolar mu gihe cyo gutwika aside z'ibinure byatumye NADH n'igipimo cya NADH ugereranyije na NAD+ bigabanuka hakurikijwe ingano yakoreshejwe. Ingano nyayo ya NAD+ yahindutse cyane gake ugereranyije na NADH, nk'uko umuntu yabyitega ku kinyabutabire gihindura imiterere imwe ikaba indi aho gukora nyinshi muri imwe muri zo.

Aho izo elekitoroni zijya harafite akamaro. Muri mitokondiriya zavanywe mu bwonko, ubururu bwa metilene ku ngano ya 100 nanomolar kugeza kuri 1 micromolar bwateje imbere ikorwa ry'ingufu igihe uruhererekane rw'ubuhumekero rwari rwabujijwe gukora, kandi icyarimwe bwongera ikorwa rya perokiside ya hidirojeni bugabanya kuyikuraho, mu bihe byose byageragejwe. Abanditsi basobanura ko iyo perokiside ya hidirojeni ituruka ku kuba ubururu bwa metilene bwakiriye elekitoroni buziha ogisijeni mu buryo butaziguye. Elekitoroni ziva muri NADH zinyuze muri iyi nzira ntizizimira. Zijya kuri ogisijeni.

Ubundi bushakashatsi ku ngingo z'umutsi wa Achilles uhuza imikaya n'igufwa busobanura iyo ngingo neza. Ubururu bwa metilene bwagaruye uburinganire bwa NAD+/NADH bwongera ikorwa rya ATP mu turemangingo tw'umutsi twangiritse no mu mbeba zakoreshejwe kwiga indwara y'uwo mutsi, kandi inyandiko y'ubushakashatsi ivuga ko igiteranyo cyose cya NAD kitagaragaje impinduka ikomeye.

Icyo ubushakashatsi ku ngingo no ku nyamaswa bwemeza

Amagerageza ane yakozwe mu myaka mirongo ine akurikirana igitekerezo kimwe kandi akagaragaza kenshi aho ubushobozi bwacyo bugarukira.

Mu kugaburira imbeba inzoga mu gihe kirekire, etanole yagabanyije ibipimo bya NAD+/NADH byo muri sitozole no muri mitokondiriya zo mu mwijima. Kongera ubururu bwa metilene mu biribwa byabujije ahanini iyo mpinduka. Ntibyagabanyije ibinure byo mu mwijima byatewe na etanole. Gukosora igipimo ntibyakosoye ingaruka. Uwo mwanzuro wo mu 1985 ukwiye kwibukwa mbere y'ikivugwa cyose cy'uko impinduka mu kwamburwa no kwakira elekitoroni ari zo zitera inyungu.

Mu turemangingo tw'umwijima no mu mbeba zagaburiwe ibiribwa birimo ibinure byinshi, ubururu bwa metilene bwazamuye igipimo cya NAD+/NADH, bwongera SIRT1, bugabanya kongerwa kw'amatsinda ya acetyl kuri PGC-1alpha, butangiza imikorere ya AMPK, kandi bugabanya kwirundanya kw'ibinure mu mwijima. Aha ingaruka zahindukanye n'igipimo. Iyo nyandiko inerekana ko ingaruka zitaguma ziyongera uko ingano yiyongera: milligrams eshatu kuri kilogram ku munsi zongereye ingano ya ADN ya mitokondiriya kurusha icumi, mu gihe ikoreshwa rya ogisijeni no kohereza ubutumwa kwa AMPK byiyongeraga uko ingano yakoreshejwe yiyongeraga.

Mu mutima urwaye diyabete, ubururu bwa metilene bwatanzwe mu mazi yo kunywa mu byumweru cumi na kimwe bwagabanyije igipimo cya NADH ugereranyije na NAD+ muri mitokondiriya z'umutima kandi bwongera imikorere ya sirtuin 3. Kongerwa kw'amatsinda ya acetyl kuri lysine kwaragabanutse ahantu 83 kuri poroteyine 34, cyane cyane izigira uruhare mu gutwara no gutwika aside z'ibinure. Igice cy'amaraso umutima usohora kuri buri gutera cyarazamutse. Ariko ubuhumekero bw'akaremangingo bushingiye kuri komplegisi I ntibwakosowe. Kandi igerageza ryo gukuraho imikorere ya jeni ryatandukanije ingaruka ebyiri byoroshye kwitiranya: impinduka y'igipimo yabaye ahanini nta sirtuin 3 ihari, mu gihe gukuraho amatsinda ya acetyl byayishingiragaho.

Mu bushakashatsi ku mutsi uhuza imikaya n'igufwa, ubururu bwa metilene bwakoreshejwe mu gihe komplegisi I yari yabujijwe gukora hakoreshejwe rotenone. Bwakomeje kugarura uburinganire bwa NAD+, ariko ntibwashoboye kubuza imihangayiko iterwa na okisidasiyo, kwangirika kw'ibikoresho biri hagati y'uturemangingo, no gutakaza ubushobozi bw'uturemangingo bwo gukomeza kubaho. Kugarura igipimo ntibyari bihagije ngo ingingo isubirane.

Urupapuro rushobora gucapwa rufite inyandiko zose zifashishijwe rukoresha iyi mirongo imwe.

Impamvu sirtuins zishyirwa muri iki kiganiro

Sirtuins zikuraho amatsinda ya acetyl kuri poroteyine, kandi zikoresha NAD+ kugira ngo zibikore. Imikorere yazo ihinduka bitewe n'uko NAD+ iboneka, bityo ikinyabutabire cyose gihindura uko iboneka kigahindura n'imikorere ya sirtuins nyuma yaho.

Iyi ni yo ngingo kwamamaza kwinshi kuvuga "ubururu bwa metilene bugenewe NAD+" gushingiraho. Ni na ho imitekerereze itangira gutandukira. Guhindura igipimo bishobora kongera imikorere ya sirtuins. Ibyo ntibivuze ko igicuruzwa gitanga NAD+, kandi ntibivuze ko ingaruka zacyo zingana n'izo gufata ikibanziriza NAD+. Gusobanura ibi bipimo hashingiwe ku kwamburwa no kwakira elekitoroni bifite ibyago byabyo byo kwibeshya, bikwiye gusomwa mbere yo kwemera kimwe muri ibyo bisobanuro.

Ibyageragejwe mu bantu

Ubururu bwa metilene bumaze imyaka mirongo bukoreshwa mu buvuzi mu bihe by'uburwayi bukaze kandi bugenzurwa: methemoglobinemia, ingaruka z'uburozi ku myakura ziterwa na ifosfamide, n'umuvuduko w'amaraso ukabije kuba muke mu gihe cyo kubagwa. Iyo ni imikoreshereze igarukira ku bihe byihariye kandi ikagenzurwa, si ibimenyetso byo kubufata mu kanwa buri munsi nk'ubufasha bwo kongera ubushobozi.

Ishakisha ryakozwe kuri iyi nyandiko ntiryabonye ubushakashatsi bwo mu bantu bupima ibikomoka ku ihindurwa rya NAD+ nyuma yo gukoresha ubururu bwa metilene mu bakorerabushake bafite ubuzima bwiza. Ibisubizo byavuzwe haruguru biva muri mitokondiriya zavanywe mu turemangingo, uturemangingo twororewe muri laboratwari, ingingo z'imbeba, n'ingingo zavanywe mu mubiri w'umuntu. Umutsi uhuza imikaya n'igufwa wavanywe mu mubiri ugakomeza kubaho mu gasahani ni intambwe y'ingirakamaro irenze gukoresha itsinda ry'uturemangingo twororerwa muri laboratwari. Ariko na byo si umuntu.

Ubushakashatsi ku bibanziriza NAD+ bukorerwa mu bantu koko, kandi ibisubizo byabwo ntibigaragaza impinduka nini. NAD+ yo mu maraso iriyongera. Ibipimo by'ubuzima biravangavanze kandi muri rusange impinduka ni nto.

Bityo, ikivugwa ku kubihuza ni ikibazo gifite ishingiro ariko igisubizo cyacyo ntikinyura: nta bushakashatsi bwatangajwe, igerageza, cyangwa uruhererekane rw'ibyabaye ku barwayi byabonetse mu gutegura iyi nyandiko byagerageje ubururu bwa metilene hamwe na nicotinamide riboside, nicotinamide mononucleotide, cyangwa NAD+ itangwa mu mutsi. Umuntu wese uvuga ko kubihuza bishyigikiwe n'ibimenyetso, cyangwa ko bikorana bikongera ingaruka z'ikindi, aba afata imyanzuro irenze ibimenyetso hashingiwe ku matsinda abiri atandukanye y'ubushakashatsi.

Gufata imyanzuro nk'iyo bishobora kwibeshya mu byerekezo byombi. Bishobora kurangwa n'icyizere kirenze, niba igiteranyo cyose kitari kikiri igipimo kibangamira imikorere igihe igipimo hagati y'imiterere yombi kimaze kugarurwa. Bishobora no koroshya ibintu birenze, kuko uko ubururu bwa metilene bukora hakurikijwe ingano bwakoreshejwe bihindura icyerekezo. Ababukoraho ubushakashatsi ubwabo babusobanura nk'ikinyabutabire gifite ingaruka zitandukanye ku ngano nto no ku nini: ingano nto zishyigikira kwakira elekitoroni, mu gihe ingano nini ziyobya elekitoroni zikazikura ku ruhererekane rw'ubuhumekero kandi zishobora gutera okisidasiyo. Kongeramo ibikoresho byinshi bikoreshwa muri iyo mikorere ntibituma uwo murongo w'ingaruka urushaho kuba nta kaga.

Hari kandi impungenge z'imikoranire n'ibindi binyabutabire zidafitanye isano na NAD+. Ubururu bwa metilene bubuza monoamine oxidase A gukora, ari yo mpamvu bushobora guteza ibyago bifitanye isano na serotonine igihe bukoreshejwe hamwe n'imiti imwe n'imwe ivura agahinda gakabije; isesengura ry'ingaruka z'uburozi ku rusobe rw'imyakura rwagati zatangajwe ryasanze ibyabaye 13 muri 14 byujuje ibipimo bya Hunter by'uburozi bwa serotonine. Bushobora kandi gutera methemoglobinemia iyo umuntu ahuye n'ingano nyinshi yabwo. Niba ufata imiti yandikiwe na muganga, ikibazo cyo kubihuza ugomba kubaza muganga wawe cyerekeye izo nzira, si uburinganire bwo kwamburwa no kwakira elekitoroni. Uko kwitonda ni na ko gukwiye ku bindi bikunze gufatirwa hamwe: izindi nyunganiramirire zifatwa hamwe n'ubururu bwa metilene zifite ibimenyetso byazo, ahanini bitarageragezwa.

Impamvu ubuziranenge bugena igerageza urimo gukora koko

Igicuruzwa cy'ubururu bwa metilene kiba ari uruvange kugeza laboratwari yemeje ko atari ko bimeze. Ikintu kitifuzwa gifite akamaro hano ni Azure B, phenothiazine yavanyweho itsinda rya methyl kandi itari ikinyabutabire kidakora. Ni irangi rigira uruhare mu kwamburwa no kwakira elekitoroni kandi risangiye na bwo imikorere shingiro y'amashanyarazi n'ubutabire, bityo igicuruzwa kirimo ingano ya Azure B ifite icyo ihindura si uburyo busukuye kurushaho cyangwa budasukuye bw'icyo kinyabutabire kimwe. Ni uruvange rutandukanye rukora ku nzira imwe, ku gipimo nta muntu wasobanuye.

Urwego rwa USP ni uburyo umuguzi abona ikinyabutabire gifite imiterere isobanuwe neza. Igicuruzwa kitari ku rwego rwa USP gishobora cyane kuba irangi ryo ku rwego rwo gusiga imyenda, kandi amarangi yo kuri urwo rwego arimo ibindi binyabutabire bituma atemerwa kuribwa cyangwa kunyobwa, harimo ibyuma biremereye n'ibisigazwa by'imiti ishongesha.

Ikinyuranyo ntikiri hagati y'inzego gusa. Abacuruzi benshi bavuga ko bubahiriza USP bapima ibyuma biremereye gusa, hanyuma bagatanga iryo tsinda rimwe ry'ibipimo nk'aho ryemeza ko bujuje ibisabwa byose. Ibisabwa byose bikubiyemo kumenya ikinyabutabire, ubuziranenge, ibinyabutabire kama bitifuzwa, ibisigazwa by'imiti ishongesha, ibindi bintu bitifuzwa byo mu bwoko bw'elementi, ibisigara nyuma yo gutwikwa, imipaka y'udukoko, n'uburozi bwo mu bwoko bwa endotoxins bukomoka kuri bagiteri. Itsinda ry'ibipimo rituzuye ntirishobora kwemeza ibitapimwe, kandi mu bitasuzumwe harimo ibinyabutabire bifitanye isano n'icyo gicuruzwa n'ibisigazwa by'imiti ishongesha.

Blupreme igura ubururu bwa metilene ku ruganda rukora imiti kandi igatangaza icyemezo cy'isesengura gikubiyemo ibisabwa byose, kugira ngo ikinyabutabire kiri mu icupa kibe ari cyo ubushakashatsi busobanura. Niba ushaka gusuzuma iyo mitekerereze ubwawe mbere yo kugura, uko wasoma ubushakashatsi ku bururu bwa metilene bisobanura icyo buri bwoko bw'ubushakashatsi bushobora n'icyo budashobora kugaragaza.

Itandukaniro rikomeza kugira ishingiro iyo risuzumwe neza

Kongeramo ikibanziriza NAD+ bihindura ingano ya NAD+ ihari. Ubururu bwa metilene buhindura icyo NAD+ isanzwe ihari irimo gukora. Icya mbere ni ikibazo cyo gutanga ibikoresho, icya kabiri ni ikibazo cy'urujya n'uruza rwabyo, kandi ubushakashatsi bushyigikira kimwe buvuga bike ku kindi.

Icyo ubururu bwa metilene bufite ni imikorere ihamye, yemejwe muri mitokondiriya zavanywe mu turemangingo no mu ngingo z'inyamaswa, ifite imbibi zisobanutse kandi zagaragajwe kenshi: guhindura igipimo si kimwe no gusana ingingo. Icyo bubura ni amagerageza yo mu bantu apima ingaruka zabwo kuri NAD+ mu bantu. Icyo nta na kimwe muri ibi byiciro gifite ni igerageza ritaziguye ryabyo byombi bifatiwe hamwe.

Ibyiciro byombi bikwiye gusuzumwa kimwe. Baza igipimo igicuruzwa kivuga ko gihindura, hanyuma ubaze ibipimo byakorewe icyo kintu mu bantu. Iyo igisubizo ari ubushakashatsi ku turemangingo, imbeba, cyangwa inzira y'imikorere ishoboka, ni ibyo gusa. Si uruvange rw'inyunganiramirire.