Intshayelelo yenqaku:

I-NAD + ibalulekile ekudalweni kwamandla emzimbeni kunye nolawulo lweenkqubo ezibalulekileyo zeselula.Nasi isizathu sokuba ibaluleke kangaka, ifunyenwe njani, kwaye ungayifumana njani ngakumbi.

Inamandla kangakanani i-NAD+

Vula nayiphi na incwadi yebhayoloji kwaye uya kufunda malunga ne-NAD+, emele i-nicotinamide adenine dinucleotide.Yicoenzyme ebalulekileyo efumaneka kwiseli nganye emzimbeni wakho ebandakanyeka kumakhulu eenkqubo zemetabolism njengamandla eselula kunye nempilo ye-mitochondrial.I-NAD + inzima emsebenzini kwiiseli zabantu kunye nezinye izilwanyana ezanyisayo, igwele kunye neebhaktheriya, kunye nezityalo.

Izazinzulu zazi nge-NAD+ okoko yaqala ukufunyanwa ngo-1906, kwaye ukusukela ngoko ukuqonda kwethu ukubaluleka kwayo kuye kwaqhubeka nokuvela.Umzekelo, i-NAD+ precursor niacin idlale indima ekuthomalaliseni i-pellagra, isifo esibulalayo esathwaxa umzantsi waseMelika ngeminyaka yoo-1900.Izazinzulu ngelo xesha zachonga ukuba ubisi kunye negwele, zombini ziqulethe izandulela ze-NAD +, zithomalalise iimpawu.Ngokuhamba kwexesha izazinzulu ziye zachonga ii-NAD + ezandulelayo - kubandakanya i-nicotinic acid, i-nicotinamide, kunye ne-nicotinamide riboside, phakathi kwezinye - ezisebenzisa iindlela zendalo ezikhokelela kwi-NAD +.Cinga nge-NAD+ yangaphambili njengeendlela ezahlukeneyo onokuthi uzithathe ukuze ufike kwindawo oya kuyo.Zonke iindlela zikusa kwindawo enye kodwa ngeendlela ezahlukeneyo zokuhamba.

Kutshanje, i-NAD+ iye yaba yimolekyuli exabisekileyo kuphando lwezenzululwazi ngenxa yendima ephambili kwimisebenzi yebhayoloji.Uluntu lwenzululwazi luye lwaphanda ukuba i-NAD + inxulumana njani nezibonelelo eziphawulekayo kwizilwanyana eziqhubeka nokukhuthaza abaphandi ukuba baguqulele ezi ziphumo ebantwini.Ke i-NAD+ idlala njani indima ebaluleke kangaka?Ngokufutshane, yi-coenzyme okanye i-molecule "yomncedi", ebophelela kwezinye ii-enzymes ukunceda ukubangela ukusabela kwinqanaba le-molecular.

Kodwa umzimba awunalo unikezelo olungapheliyo lwe-NAD +.Enyanisweni, iyancipha ngokukhula.Imbali yophando lwe-NAD +, kunye nokusekwa kwayo kutshanje kuluntu lwesayensi, ivule iingcango zezazinzulu ukuba ziphande ngokugcina amanqanaba e-NAD + kunye nokufumana ngaphezulu kwe-NAD +.

Yintoni iMbali ye-NAD+?

I-NAD + yaqala ukuchongwa uSir Arthur Harden kunye noWilliam John Young ngo-1906 xa bobabini babejolise ekuqondeni ngcono ukuvutshelwa - apho igwele lidibanisa iswekile kunye nokudala utywala kunye ne-CO2.Kuthathe phantse iminyaka eyi-20 ukuqatshelwa ngakumbi kwe-NAD +, xa uHarden wabelana ngeBhaso leNobel kwiChemistry ngo-1929 kunye noHans von Euler-Chelpin ngomsebenzi wabo wokuvubela.U-Euler-Chelpin uchonge ukuba isakhiwo se-NAD + senziwe ngee-nucleotides ezimbini, iibhloko zokwakha ze-nucleic acids, ezenza i-DNA.Ukufumanisa ukuba ukubila, inkqubo yemetabolism, kuxhomekeke kwi-NAD+ kwafanekisela into esiyaziyo ngoku nge-NAD+ edlala indima ebalulekileyo kwiinkqubo ze-metabolic ebantwini.

U-Euler-Chelpin, kwintetho yakhe yeBhaso likaNobel ngowe-1930, wabhekisa kwi-NAD+ njenge-cosymase, into eyayikade ibizwa ngokuba, ebonisa amandla ayo.“Isizathu sokuba senze umsebenzi omninzi kangaka ekusulungekisweni nasekumiselweni komgaqo-siseko wale nto,” utshilo, “sesinye sezona zinto zixhaphakileyo nezibaluleke kakhulu kwizityalo nakwizilwanyana.”

U-Otto Heinrich Warburg - owaziwa ngokuba "yimpembelelo yeWarburg" - watyhalela phambili isayensi kwiminyaka yoo-1930, ngophando olucacisa ngakumbi i-NAD+ edlala indima kwi-metabolic reaction.Kwi-1931, i-chemist Conrad A. Elvehjem kunye no-CK Koehn bachonge ukuba i-nicotinic acid, i-precursor ye-NAD +, yayiyinto yokunciphisa i-pellagra.UGqirha weNkonzo yezeMpilo yase-United States uJoseph Goldberger wayechonge ngaphambili ukuba esi sifo sibulalayo sasiqhagamshelene nento engekhoyo ekutyeni, awathi ke wayibiza ngokuba yiPPF "ye-pellagra yokuthintela."UGoldberger usweleke ngaphambi kokuba kufunyaniswe ukuba yi-nicotinic acid, kodwa igalelo lakhe lakhokelela ekubhaqweni, nto leyo eyathi yazisa umthetho ogunyazisa ukuqiniswa komgubo kunye nerayisi kumazwe ngamazwe.

Kwiminyaka elishumi eyalandelayo, u-Arthur Kornberg, owathi kamva waphumelela ibhaso likaNobel ngokubonisa indlela i-DNA kunye ne-RNA eyenziwa ngayo, ifunyenwe i-NAD synthetase, i-enzyme eyenza i-NAD +.Olu phando luphawule ukuqala kokuqonda iibhloko zokwakha ze-NAD +.Ngo-1958, izazinzulu uJack Preiss kunye noPhilip Handler bachaza into ngoku eyaziwa ngokuba yiPreiss-Handler pathway.Indlela ibonisa indlela i-nicotinic acid - uhlobo olufanayo lwe-vitamin B3 eyanceda ukunyanga i-pellagra - iba yi-NAD +.Oku kwanceda izazinzulu ukuba ziqonde ngakumbi indima ye-NAD + ekutyeni.UHandler kamva wafumana iMbasa yeSizwe yeSayensi kuMongameli uRonald Reagan, owakhankanya “igalelo elibalaseleyo likaHandler kuphando lwebhayoloji…

Ngelixa izazinzulu ziye zakuqonda ukubaluleka kwe-NAD +, zazingekafumani mpembelelo yayo entsonkothileyo kumgangatho weselula.Itekhnoloji ezayo kuphando lwesayensi edityaniswe nokuqondwa ngokubanzi kokubaluleka kwe-coenzyme ekugqibeleni yakhuthaza izazinzulu ukuba ziqhubeke nokufunda imolekyuli.

Isebenza njani i-NAD+ emzimbeni?

I-NAD+ isebenza njengebhasi yokutshibilika, idlulisela ii-electron ukusuka kwimolekyuli enye ukuya kwenye ngaphakathi kweeseli ukwenza zonke iintlobo zokuphendula kunye neenkqubo.Ngomlingani wayo weemolekyuli, i-NADH, le molekyuli ibalulekileyo ithatha inxaxheba kwiindlela ezahlukeneyo zokusabela ezenza amandla eseli yethu.Ngaphandle kwamanqanaba aneleyo e-NAD+, iiseli zethu azinakukwazi ukuvelisa nawaphi na amandla ukuze ziphile kwaye zenze imisebenzi yazo.Eminye imisebenzi ye-NAD + ibandakanya ukulawula isigqi sethu se-circadian, esilawula ukulala / ukuvuka komzimba wethu.

Njengoko siguga, amanqanaba e-NAD + awela, ebonisa iziphumo ezibalulekileyo ekusebenzeni kwe-metabolic kunye nezifo ezinxulumene neminyaka.Umonakalo we-DNA uqokelela kunye neebhola zekhephu ngokuguga.

Kwenzeka ntoni xa amanqanaba e-NAD + encitshisiwe?

Izifundo ezininzi zibonisa amanqanaba ancitshisiweyo e-NAD + kwiimeko eziphazamisekileyo zezondlo, ezinjengokutyeba, kunye nokwaluphala.Ukunciphisa amanqanaba e-NAD + kunokukhokelela kwiingxaki zemetabolism.Ezi ngxaki zinokukhokelela kukuphazamiseka, kubandakanya ukutyeba kakhulu kunye nokumelana ne-insulin.Ukutyeba kakhulu kubangela isifo seswekile kunye noxinzelelo lwegazi oluphezulu.

Iziphazamiso zeMetabolic ezibangelwa linqanaba elisezantsi le-NAD + lehla.Uxinzelelo lwegazi oluphezulu kunye nokunye ukwehla kokusebenza kwentliziyo kunokuthumela amaza oxinzelelo omonakalo kwingqondo anokuthi akhokelele kukuphazamiseka kwengqondo.

Ukujolisa kwi-NAD+ imetabolism lungenelelo olusebenzayo lwesondlo ekukhuseleni ngokuchasene ne-metabolic kunye nezinye izifo ezinxulumene nobudala.Amaqela amaninzi enze izifundo ezibonisa ukuxhaswa nge-NAD+ boosters kuphucula ukuxhathisa kwe-insulin ekutyebeni.Kwiimodeli zempuku zezifo ezinxulumene neminyaka, ukongeza nge-NAD + boosters kuphucula iimpawu zezifo.Oku kuphakamisa amanqanaba e-NAD + ancitshisiweyo ngobudala anokuba negalelo ekuqalekeni kwezifo ezinxulumene nobudala.

Ukuthintela ukwehla kwe-NAD + kunika isicwangciso esithembisayo sokulwa nokuphazamiseka kwemetabolism ngobudala.Njengoko amanqanaba e-NAD + ehla ngokuhamba kweminyaka, oku kunokukhokelela ekunciphiseni ukulungiswa kwe-DNA, impendulo yoxinzelelo lweselula, kunye nolawulo lwemetabolism yamandla.

IiNzuzo ezinokubakho

I-NAD + ibalulekile kulondolozo lwe-mitochondrial yeentlobo kunye nokulawulwa kofuzo malunga nokuguga.Nangona kunjalo, inqanaba le-NAD + emzimbeni wethu lehla kakhulu ngenxa yobudala.“Njengoko sikhula, siphulukana ne-NAD +.Xa ufikelela kwiminyaka engama-50 ubudala, umalunga nesiqingatha somgangatho owawunawo xa wawuneminyaka engama-20 ubudala,” watsho njalo uDavid Sinclair weYunivesithi yaseHarvard kudliwano-ndlebe.

Uphononongo lubonise ukuhla kwemolekyuli enxulumana nezifo ezinxulumene nobudala kubandakanya ukuguga okukhawulezileyo, ukuphazamiseka kwemetabolism, isifo sentliziyo, kunye ne-neurodegeneration.Amanqanaba asezantsi e-NAD + anxulunyaniswa nesifo esinxulumene nobudala ngenxa yokusebenza kancinci kwemetabolism.Kodwa ukuzalisa amanqanaba e-NAD + kubonise iziphumo zokuchasa ukwaluphala kwiimodeli zezilwanyana, zibonisa iziphumo ezithembisayo ekubuyiseni umva kwezifo ezinxulumene nobudala, ukwandisa ubomi kunye nempilo.

Ukuguga

Eyaziwa ngokuba “ngabagadi begenomes,” iisirtuins ziyimizila yemfuza ekhusela izinto eziphilayo, ukusuka kwizityalo ukuya kwizilwanyana ezanyisayo, ekuwohlokeni nakwizifo.Xa imizila yemfuza ibona ukuba umzimba uphantsi koxinzelelo lomzimba, njengokuzilolonga okanye ukulamba, ithumela imikhosi ukuya kukhusela umzimba.I-Sirtuins igcina ingqibelelo ye-genome, ikhuthaza ukulungiswa kwe-DNA kwaye ibonise iipropati ezinxulumene nokuguga kwizilwanyana zemodeli ezifana nokwandisa ubomi.