Ergothioneine, kavalo wakuda m'dziko loletsa kukalamba 

Ergothioneine (EGT) idasiyanitsidwa koyamba ndi bowa wa ergot ndi wasayansi Charles Tanret mu 1909, chifukwa chake dzina lake. Ndi chochokera mwachilengedwe cha amino acid chomwe chimagawidwa kwambiri mu bowa, zomera zina, ndi nyama. M’zakudya za anthu, bowa, mbewu, ndi zakudya zina za m’nyanja ndizo magwero ake aakulu. Pofufuza mozama ndi sayansi yamakono, zotsatira zochititsa chidwi za ergothioneine zawonekera pang'onopang'ono.

Mfundo zotsutsana ndi ukalamba ndi njira zogwirira ntchito

Zotsatira ziwiri za antioxidant

Kusakaza mwachindunji kwa ma radicals aulere: EGT imatha kusokoneza mwachangu mitundu yosiyanasiyana ya okosijeni (ROS) ndi mitundu yokhazikika ya nayitrogeni (RNS), kuphatikiza superoxide anion (O₂⁻), hydrogen peroxide (H₂O₂), hydroxyl radicals (·OH), ndi singlet oxygen (¹O₂). Izi zakhala zikutsimikiziridwa kwathunthu mu kuyesa kwa in vitro.

Ubwino wofananiza

Kuwongolera kwa antioxidant system system: EGT imayang'anira kufotokozera kwa majini otsika a antioxidant (monga HO-1, NQO1, SOD, ndi CAT) poyambitsa KEAP1-NRF2 njira yowonetsera. Kusintha kwa nyukiliya kwa NRF2 kumayendetsedwa ndi njira zowonetsera PI3K / AKT ndi PKC, ndipo EGT ikhoza kulimbikitsa kumasulidwa ndi kusuntha kwa nyukiliya kwa NRF2 mwa kusintha thiol sensor ya KEAP1.

Ntchito Yoteteza mu Genome Stability

Kuchepetsa Kuwonongeka kwa DNA: EGT imaletsa bwino kuwonongeka kwa DNA kwa ROS- ndi RNS, makamaka mu mitochondrial DNA (mtDNA). Kafukufuku wawonetsa kuti ma cell omwe alibe zonyamula za EGT amawonetsa kuwonongeka kwakukulu kwa DNA.

Kulimbikitsa Kukonza kwa DNA: EGT sikuti imangotengera kuwala kwa ultraviolet (UV) komanso imalimbikitsa kukonza kwa DNA pambuyo pa kuyatsa kwa UV, kuteteza maselo akhungu kuti asawonongeke.

Kuwongolera Kusintha kwa Epigenetic

Kukhudza Kaphatikizidwe ka Methyl Donor SAM: EGT imakhudza mwachindunji kupezeka kwa S-adenosylmethionine (SAM) poyang'anira milingo ya glutathione (GSH), potero imayendetsa ntchito za DNA methyltransferases (DNMTs) ndi histone methyltransferases (HMTs).

Kusunga Iron Ion Homeostasis Yaulere: EGT imasunga chitsulo chaulere cha ion homeostasis pochotsa ROS, motero kuwonetsetsa kuti ma demethylases (monga TETs ndi JmjC).

Njira zolumikizirana ndi Sirtuin:

Kuwongolera kwa SIRT1 / SIRT6 kufotokoza: EGT imachedwetsa endothelial cell senescence ndipo imapangitsa kuti necrotizing apoptosis m'maselo a khansa yapakatikati mwa kuwongolera mawonekedwe a SIRT1 ndi SIRT6.

Kusunga milingo ya NAD⁺: EGT imakulitsa ntchito ya Sirtuin powongolera mawonekedwe a redox ya ma cell ndikusunga chiŵerengero cha NAD⁺/NADH.

Kukonzekera Method

Njira Yotulutsira Zachilengedwe:

EGT imapezeka muzinthu zachilengedwe monga bowa wodyedwa, ergot, chimanga, ndi minofu yanyama. Bowa wodyedwa ali ndi kuchuluka kwa EGT ndipo ndi gwero lofunikira la EGT.

Komabe, zomwe zili mu EGT pazachilengedwe nthawi zambiri zimakhala zotsika kwambiri, zomwe zimafunikira zida zambiri zopangira, zomwe zimapangitsa kuti pakhale ndalama zambiri zochotsa. Komanso, nkhani monga kuchuluka kwa zonyansa ndi zotsalira za mankhwala muzinthu zopangira zimachepetsa kugwiritsa ntchito njira zopangira zinthu zachilengedwe m'mafakitale.

Chemical Synthesis Njira: Kaphatikizidwe ka mankhwala achikale a EGT amagwiritsa ntchito histidine ngati poyambira, kupanga EGT mu njira yamadzimadzi kudzera munjira zingapo kuphatikiza thiolation, thioprotection, methylation, ndi deprotection. Njirayi ili ndi njira yayitali yopangira komanso zokolola zochepa. M'zaka zaposachedwa, kafukufuku atengera njira za biosynthetic kuti apititse patsogolo kaphatikizidwe ka mankhwala a EGT. Mwachitsanzo, Erdelmeier et al. adagwiritsa ntchito histidine betaine, cysteine, ndi mercaptopropionic acid monga zida zoyambira kupanga EGT pogwiritsa ntchito njira yosavuta ya mphika umodzi, kupewa kuyambitsa magulu a thioprotective, kufupikitsa njira yopangira, ndikuwongolera zokolola.

Kaphatikizidwe ka mankhwala kumabweretsanso zovuta zina. Mwachitsanzo, chirality wa α-carbon mu gulu carboxyl mosavuta racemization pansi acidic kapena zamchere mikhalidwe, kupangitsa kukhala kovuta kupeza mkulu-kuwala-kuyera EGT. Kuphatikiza apo, zopangira zomwe zimafunikira pakuphatikizika kwamankhwala ndizokwera mtengo, zoyambira 2-mercaptoimidazole ndizovuta kukonzekera, ndipo kukonzanso pambuyo pake kumakhala kovuta. Chifukwa chake, ofufuza akuyenera kukhathamiritsa ndikuwongolera njira zophatikizira mankhwala kuti akwaniritse zosowa zamakampani akuluakulu.

Microbial nayonso mphamvu: Kupeza EGT kudzera mu biosynthesis kuli ndi zabwino monga zopangira zopezeka mosavuta komanso zotsika mtengo, ndipo yakhala njira yayikulu yokonzekera EGT m'zaka zaposachedwa. M'chilengedwe, EGT ilipo kudzera m'njira ziwiri: aerobic biosynthesis ndi anaerobic biosynthesis.

Aerobic Biosynthesis ya EGT

Kafukufuku wambiri wafotokoza njira ya biosynthetic ya EGT. Kwenikweni, njira ya aerobic biosynthetic ya EGT imatha kugawidwa m'njira za bakiteriya ndi mafangasi. Seebeck et al. adafotokozera ndikumanganso njira ya aerobic biosynthetic ya EGT mu vitro mu Mycobacterium smegmatis, kuzindikiritsa majini asanu omwe adakhudzidwa ndi njirayo: EgtA, EgtB, EgtC, EgtD, ndi EgtE. Majini awa amaphatikiza glutamylcysteine ​​​​synthase (EgtA), Fe2+ -odalira oxidase (EgtB), gamma-glutamyl transferase (EgtC), S-adenosyl methionine (SAM) -yodalira histidine methyltransferase (EgtD), ndi pyridoxantglyespendent-espendent-dependent. Pochita izi, EgtA imathandizira kukhazikika kwa glutamate ndi cysteine ​​​​kupanga γ-glutamylcysteine; EgtB imathandizira kulumikizana kwa okosijeni pamaso pa okosijeni ndi ferrous sulfate, ndikuwonjezera gulu la thiol kuchokera ku γ-glutamylcysteine ​​​​kumbali yam'mbali ya histidine betaine (yopangidwa kuchokera ku histidine ndi SAM yopangidwa ndi EgtD); EgtC ndiye catalyzes zina mapangidwe histidine betaine cysteine ​​​​sulfoxide; Pomaliza, EgtE imathandizira kuchotsa pyruvate ndi ammonia kupanga EGT.

Munjira ya fangasi ya biosynthetic, EGT imakhudzanso majini awiri a synthase, Egt1 ndi Egt2. Bello et al. adazindikira synthase yeniyeni, NcEgt1, mu *Neurospora crassa*, yomwe ili ndi madambwe ofanana ndi omwe ali mu *Mycobacterium smegmatis*'s EgtB ndi EgtD. Egt1 nawo mbali ziwiri chothandizira anachita: choyamba, izo catalyzes kutembenuka kwa histidine kuti histidine betaine, ndiyeno catalyzes kuphatikiza histidine betaine ndi cysteine ​​​​kupanga histidine betaine cysteine ​​​​sulfoxide. Zofanana ndi EgtE, Egt2 imathandizira mapangidwe a EGT kuchokera ku histidine, betaine, ndi cysteine ​​​​sulfoxide. Monga zikuwonekera pachithunzichi, chifukwa ma enzyme awiri okha ndi omwe akukhudzidwa, njira ya biosynthetic ya EGT mu bowa ndiyosavuta kuposa mabakiteriya.

Anaerobic Biosynthesis ya EGT

Anaerobic biosynthesis ya EGT idanenedwa mu bakiteriya wamatope (Chlorobium limicola), pomwe EGT biosynthesis imakwaniritsidwa kudzera munjira ziwiri zosagwirizana ndi okosijeni. Burn et al. adazindikira methyltransferase (EanA) ndi sulfotransferase (EanB) mu bakiteriya yamatope ya anaerobic. Monga momwe chithunzichi, EanA imathandizira kutembenuka kwa histidine kukhala histidine betaine, ndiyeno EanB, pansi pa zikhalidwe za anaerobic, imasamutsa atomu ya sulfure kupita ku mphete ya imidazole ya histidine betaine kupanga EGT. Ngakhale njira ya anaerobic biosynthesis ndiyosavuta, milingo ya EanA ndi EanB ndiyotsika kwambiri kuposa ya EgtD ndi EgtB munjira ya aerobic biosynthesis. Chifukwa chake, njira ya aerobic biosynthesis imakhalabe njira yayikulu ya EGT biosynthesis.

Zoyembekeza zofunsira

Ergothioneine ali ndi mphamvu zowononga antioxidant komanso zoletsa kukalamba, ndipo ali ndi chiyembekezo chogwiritsa ntchito pazakudya, zodzoladzola, chakudya chogwira ntchito, komanso mafakitale a biopharmaceutical. Kugwiritsa ntchito kwake pantchito yokongola komanso yosamalira khungu kumakhala kodziwika kwambiri, ndikupangitsa kuti ikhale yofunika kwambiri pazinthu zolimbana ndi ukalamba.

Ubwino wake waukulu ndi:

1. Antioxidant ndi Anti-kukalamba: Mphamvu yamphamvu ya antioxidant ya Ergothioneine imalimbana bwino ndi ma free radicals, imachepetsa kuwonongeka kwa okosijeni m'maselo a khungu, imachepetsa ukalamba wa khungu, imachepetsa makwinya ndi kugwa.
2. Kuyera ndi Kuchepetsa Mawanga: Kumalepheretsa kupanga ndi kuyika kwa melanin, kumapangitsa kuti khungu likhale losalala komanso losawoneka bwino, komanso limawunikira khungu.
3. Anti-inflammatory and Soothing: Amachepetsa kutupa kwa khungu, amachepetsa kufiira ndi kuyabwa, amalimbitsa chitetezo cha khungu, amalimbitsa chitetezo chake.
4. Kunyowa ndi Kukonza: Kumawongolera bwino ntchito yotchinga pakhungu, kumapangitsa kuti khungu liziyenda bwino, kumathandizira kukonza ndikukonzanso khungu lowonongeka.
5. Photoprotection ndi Chitetezo ku Kuwonongeka kwa UV: Ma radiation a Ultraviolet ndi amodzi mwazinthu zomwe zimayambitsa ukalamba wa khungu. Ergothioneine ikhoza kuchepetsa kuwonongeka kwa khungu chifukwa cha cheza cha ultraviolet, kuteteza khungu ku photoaging, komanso kuteteza dzuwa.

Fotokozerani mwachidule

Ergothioneine, ndi njira yake yapadera ya antioxidant ndi mitundu yosiyanasiyana ya ntchito, ikukonzanso makampani odana ndi ukalamba. Ndi kupita patsogolo kwa biology yopanga komanso kafukufuku wozama wazachipatala, zitha kukhala chimodzi mwazinthu zazikulu zomwe zimathandizira kuchedwetsa ukalamba ndikuwongolera moyo wabwino. Kwa ogula, kusankha zinthu zoyera kwambiri, zopangidwa mwasayansi za ergothioneine zingakhale chinsinsi cholimbana ndi zotsatira za nthawi.