Ergothioneine, ihashe elimnyama kwihlabathi elichasene nokuguga 

I-Ergothioneine (EGT) yabekwa yodwa okokuqala kwi-ergot fungi yisazinzulu uCharles Tanret ngo-1909, kungoko igama layo. Yenzeka ngokwendalo evela kwi-amino acid esasazwa ngokubanzi kumngundo, kwezinye izityalo, kunye nezilwanyana. Kukutya kwabantu, amakhowa, iinkozo, nokutya okuthile kwaselwandle yeyona mithombo yako iphambili. Ngophando olunzulu lwesayensi yanamhlanje, iziphumo ezimangalisayo ze-ergothioneine ziye zavela ngokuthe ngcembe.

Imigaqo yokulwa nokuguga kunye neendlela zokwenza

Iziphumo ezimbini ze-antioxidant

Ukucocwa ngokuthe ngqo kweeradicals zasimahla: I-EGT inokunciphisa ngokukhawuleza iintlobo ezahlukeneyo zeoksijini esebenzayo (i-ROS) kunye neentlobo zenitrogen esebenzayo (RNS), kubandakanya i-superoxide anion (O₂⁻), i-hydrogen peroxide (H₂O₂), i-hydroxyl radicals (·OH), kunye ne-oksijini eyodwa (¹O₂). Esi siphumo sokutshabalalisa ngokuthe ngqo siqinisekisiwe ngokupheleleyo kwimifuniselo ye-in vitro.

Iinzuzo zokuthelekisa

Ukulawulwa kwenkqubo yokukhusela i-antioxidant: I-EGT iphakamisa ukubonakaliswa kwe-antioxidant genes esezantsi (efana ne-HO-1, NQO1, SOD, kunye ne-CAT) ngokuvula indlela yokubonisa i-KEAP1-NRF2. Ukutshintshwa kwenyukliya ye-NRF2 ilawulwa yi-PI3K / AKT kunye ne-PKC yeendlela zokubonisa, kwaye i-EGT inokukhuthaza ukukhululwa kunye nokuhanjiswa kwenyukliya ye-NRF2 ngokumodareyitha i-thiol sensor ye-KEAP1.

Indima yoKhuseleko kuZinzo lweGenome

Ukunciphisa Umonakalo we-DNA: I-EGT inqanda ngokufanelekileyo i-ROS- kunye ne-RNS-induced DNA umonakalo, ngokukodwa kwi-mitochondrial DNA (mtDNA). Izifundo zibonise ukuba iiseli eziswele abathuthi be-EGT zibonisa amanqanaba aphezulu omonakalo weDNA.

Ukukhuthaza ukulungiswa kwe-DNA: I-EGT ayifunxa kuphela i-ultraviolet (UV) imitha kodwa ikhuthaza ukulungiswa kwe-DNA emva kokukhanya kwe-UV, ukukhusela iiseli zesikhumba kwi-photodamage.

Ukulawulwa kokuguqulwa kwe-Epigenetic

Ukuchaphazela i-Synthesis ye-Methyl Donor SAM: I-EGT ichaphazela ngokungathanga ngqo ukufumaneka kwe-S-adenosylmethionine (SAM) ngokulawula amanqanaba e-glutathione (GSH), ngaloo ndlela ilawula umsebenzi we-DNA methyltransferases (DNMTs) kunye ne-histone methyltransferases (HMTs).

Ukugcina i-Iron Ion Homeostasis yasimahla: I-EGT igcina i-iron ion homeostasis yasimahla ngokukhupha i-ROS, ngaloo ndlela iqinisekisa umsebenzi we-demethylases (njenge-TETs kunye ne-JmjC).

Unxibelelwano kunye nendlela yomqondiso we-Sirtuin:

Ukunyangwa kwe-SIRT1 / SIRT6 yokubonisa: I-EGT ilibazisa i-endothelial cell senescence kwaye yenza i-necrotizing apoptosis kwiiseli zomhlaza we-colorectal ngokuphakamisa ukubonakaliswa kwe-SIRT1 kunye ne-SIRT6.

Ukugcina amanqanaba e-NAD⁺: I-EGT iphucula umsebenzi we-Sirtuin ngokulawula imeko ye-redox yeselula kunye nokugcina umlinganiselo we-NAD⁺/NADH.

Ukulungiselela Mindlela

Indlela yokutsalwa kwendalo:

I-EGT ifumaneka kwiimveliso zendalo ezifana nokungunda okutyiwayo, iergot, iisiriyeli, kunye nezihlunu zezilwanyana. Iifungi ezityiwayo zinomxholo ophezulu we-EGT kwaye zingumthombo obalulekileyo we-EGT.

Nangona kunjalo, umxholo we-EGT weemveliso zendalo uphantsi kakhulu, ufuna izixa ezikhulu zemathiriyeli ekrwada ukuze zitsalwe, okukhokelela kwiindleko eziphezulu zokutsalwa. Ngaphaya koko, imiba efana namanqanaba aphezulu okungcola kunye neentsalela zamachiza kwimathiriyeli ekrwada iyanciphisa usetyenziso lwemizi-mveliso yeendlela zokutsalwa kwemveliso yendalo.

Indlela yokuHlanganisa imichiza: Ukwenziwa kweekhemikhali zemveli ze-EGT zisebenzisa i-histidine njengesixhobo sokuqala, ukudibanisa i-EGT kwisisombululo samanzi ngamanyathelo amaninzi abandakanya i-thiolation, i-thioprotection, i-methylation, kunye nokukhusela. Le ndlela inendlela ende yokwenziwa kunye nesivuno esiphantsi. Kwiminyaka yakutshanje, izifundo ziye zalinganisa iindlela ze-biosynthetic zokuphucula i-chemical synthesis ye-EGT. Ngokomzekelo, u-Erdelmeier et al. isebenzise i-histidine betaine, i-cysteine, kunye ne-mercaptopropionic acid njengezixhobo zokuqalisa ukudibanisa i-EGT kusetyenziswa ukusabela kwembiza enye eyenziwe lula, ukuphepha ukuqaliswa kwamaqela e-thioprotective, ukunciphisa indlela yokwenziwa, kunye nokuphucula isivuno.

Ukwenziwa kweekhemikhali kukwavelisa imingeni ethile. Umzekelo, i-chirality ye-α-carbon kwiqela le-carboxyl ikhokelela ngokulula kwi-racemization phantsi kweemeko ze-acidic okanye i-alkaline, isenza kube nzima ukufumana i-EGT ephezulu ye-optical-purity. Ngaphaya koko, izinto ezifunekayo zokwenziwa kweekhemikhali ziyabiza, i-2-mercaptoimidazole inzima ukuyilungisa, kwaye i-post-processing yemveliso nayo ingumceli mngeni. Ke ngoko, abaphandi kufuneka baphucule kwaye baphucule iindlela zokwenziwa kweekhemikhali ukuhlangabezana neemfuno zemveliso yemizi-mveliso emikhulu.

Ukuvundiswa kweMicrobial: Ukufumana i-EGT ngokusebenzisa i-biosynthesis kuneengenelo ezifana nemathiriyeli ekrwada efumaneka lula kunye neendleko eziphantsi ngokwentelekiso, kwaye ibe yeyona ndlela iphambili yamalungiselelo e-EGT kwiminyaka yakutshanje. Ngokwendalo, i-EGT ikhona ngeendlela ezimbini: i-aerobic biosynthesis kunye ne-anaerobic biosynthesis.

I-Aerobic Biosynthesis ye-EGT

Izifundo ezininzi ziye zacacisa inkqubo ye-biosynthetic ye-EGT. Ngokusisiseko, indlela ye-aerobic biosynthetic ye-EGT inokwahlulwa ibe ziindlela zebhaktiriya kunye nokungunda. Seebeck et al. yacaciswa kwaye yaphinda yakhiwa indlela ye-aerobic biosynthetic ye-EGT kwi-vitro kwi-Mycobacterium smegmatis, ichaza imizila yemfuza emihlanu ebandakanyekayo kwindlela: i-EgtA, i-EgtB, i-EgtC, i-EgtD, kunye ne-EgtE. Ezi genes encode glutamylcysteine ​​​​synthase (EgtA), Fe2+-exhomekeke kwi-oxidase (EgtB), i-gamma-glutamyl transferase (EgtC), i-S-adenosyl methionine (SAM) -ixhomekeke kwi-histidine methyltransferase (EgtD), kunye ne-pyridoxantly-Esependent-Esependent-Esependent. Kule nkqubo, i-EgtA ivuselela ukuqina kwe-glutamate kunye ne-cysteine ​​​​ukuvelisa i-γ-glutamylcysteine; I-EgtB ivuselela ukudibanisa kwe-oxidative kubukho be-oksijini kunye ne-ferrous sulfate, yongeza iqela le-thiol ukusuka kwi-γ-glutamylcysteine ​​​​kwi-side chain ye-histidine betaine (eyenziwe kwi-histidine kunye ne-SAM eyenziwa yi-EgtD); I-EgtC emva koko ivuselela ukwakheka okuqhubekayo kwe-histidine betaine cysteine ​​​​sulfoxide; ekugqibeleni, EgtE catalyzes ukususwa pyruvate kunye ammonia ukuvelisa EGT.

Kumngundo we-biosynthetic pathway, i-EGT ibandakanya ubukhulu becala iijini ezimbini ze-synthase, i-Egt1 kunye ne-Egt2. UBello et al. ichonge i-synthase ethile, i-NcEgt1, kwi-*Neurospora crassa*, equlethe imimandla efana naleyo ikwi-EgtB kunye ne-EgtD ye-Mycobacterium smegmatis*. I-Egt1 ithatha inxaxheba kumanyathelo amabini okuvuselela amandla: okokuqala, yenza ukuguqulwa kwe-histidine ibe yi-histidine betaine, kwaye emva koko ivuselela indibaniselwano ye-histidine betaine kunye ne-cysteine ​​​​ukwenza i-histidine betaine cysteine ​​​​sulfoxide. Ngokufana ne-EgtE, i-Egt2 ivuselela ukwakheka kwe-EGT ukusuka kwi-histidine, i-betaine, kunye ne-cysteine ​​​​sulfoxide. Njengoko kubonisiwe kumzobo, kuba zimbini kuphela ii-enzymes ezibandakanyekayo, indlela ye-biosynthetic ye-EGT kumngundo ilula kakhulu kunaleyo kwiibhaktheriya.

I-Anaerobic Biosynthesis ye-EGT

I-anaerobic biosynthesis ye-EGT iye yaxelwa kwibhaktiriya yodaka engqongqo (i-Chlorobium limicola), apho i-biosynthesis ye-EGT iphunyezwa ngokusabela ngamanyathelo amabini ngaphandle kweoksijini. Tshisa et al. ichonge i-methyltransferase (EanA) kunye ne-sulfotransferase (EanB) kule bhaktiriya yodaka lwe-anaerobic. Njengoko kubonisiwe kumzobo, i-EanA ivuselela ukuguqulwa kwe-histidine kwi-histidine betaine, kwaye emva koko i-EanB, phantsi kweemeko ze-anaerobic, idlulisela i-athomu yesulfure kwiringi ye-imidazole ye-histidine betaine ukwenza i-EGT. Nangona indlela ye-anaerobic biosynthesis ilula, amazinga e-catalytic e-EanA kunye ne-EanB asezantsi kakhulu kunalawo e-EgtD kunye ne-EgtB kwindlela ye-aerobic biosynthesis. Ke ngoko, indlela ye-aerobic biosynthesis ihlala iyeyona ndlela iphambili ye-EGT biosynthesis.

Amathemba esicelo

I-Ergothioneine ineepropathi ezinamandla ze-antioxidant kunye ne-anti-aging, kwaye inethuba elibanzi lokusebenzisa ukutya, izithambiso, ukutya okusebenzayo, kunye namashishini e-biopharmaceutical. Ukusetyenziswa kwayo kwintsimi yobuhle kunye ne-skincare ibonakala ngokukhethekileyo, iyenza ibe yinto ebalulekileyo kwiimveliso ezichasene nokuguga.

Iinzuzo zayo eziphambili ziquka:

1. I-Antioxidant kunye ne-Anti-Aging: I-Ergothioneine inamandla okulwa ne-antioxidant ngokufanelekileyo ukulwa ne-radicals yamahhala, iyanciphisa umonakalo owenziwe nge-oxidative kwiiseli zesikhumba, ukulibazisa ukuguga kwesikhumba, kunye nokunciphisa imibimbi kunye nokugubha.
2. Ubumhlophe kunye nokuNcitshiswa kwamabala: Inqanda imveliso ye-melanin kunye nokubekwa, iphucula umbala kunye nobumnyama, kwaye ikhanyisa ithoni yesikhumba.
3. I-Anti-inflammatory and Soothing: Inciphisa ukudumba kwesikhumba, ikhulula ngokufanelekileyo ububomvu kunye nokurhawuzelelwa, yomeleza umqobo wokukhusela ulusu, kwaye inyusa ukuxhathisa kwayo.
4. Ukuthambisa kunye nokulungiswa: Ukuphucula ngokufanelekileyo umsebenzi wokuthintela ulusu, uphucula ukuhanjiswa kwesikhumba, kwaye ukhuthaza ukulungiswa kunye nokuvuselelwa kolusu olonakeleyo.
5. Ukukhuselwa kwefoto kunye nokuKhuselwa kumonakalo we-UV: Imitha ye-Ultraviolet yenye yezona zinto zibangela ukuguga kwesikhumba. I-Ergothioneine inokunciphisa umonakalo wolusu obangelwa yimitha ye-ultraviolet, ukukhusela ulusu kwi-photoaging, kwaye inikeze ukhuseleko olusebenzayo elangeni.

Shwankathela

I-Ergothioneine, kunye ne-antioxidant ye-antioxidant ekhethekileyo kunye noluhlu olubanzi lwezicelo, ihlaziya ishishini lokulwa nokuguga. Ngokuphumelela kwibhayoloji yokwenziwa kunye nophando olunzulu lwezonyango, inokuba sesinye sezithako ezingundoqo zokulibazisa ukwaluphala kunye nokuphucula umgangatho wobomi. Kubathengi, ukukhetha ukucoceka okuphezulu, iimveliso ze-ergothioneine ezenziwe ngokwesayensi zinokuba ngundoqo ekulweni nemiphumo yexesha.