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1kits （10Ibikoresho）
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NAD ＋ Imiterere
Inkomoko: PubChem |
Urukurikirane: N / A. Imiterere ya molekulari: C 21H 27N 7O 14P.2 Uburemere bwa molekuline: 663.4 g / mol Umubare CAS: 53-84-9 PubChem CID: 5892 Synonyme: nadide ； coenzyme I ； beta-NAD ； Codehydrogenase I. |
NAD ＋ Ubushakashatsi
NAD + ni iki?
NAD + (Nicotinamide Adenine Dinucleotide) ni coenzyme ikomeye igaragara cyane mubinyabuzima. Ikorwa no guhuza adenosine ribonucleotide na nicotinamide ribonucleotide binyuze mumatsinda ya fosifate. Nka coenzyme yibanze muri redox reaction, NAD + igira uruhare runini muri metabolism selile. Irashobora guhinduka hagati ya okiside (NAD +) na leta yagabanutse (NADH), ikagira uruhare mubikorwa byo guhinduranya ingufu nka glycolysis, cycle citric cycle, na fosifori ya okiside, ifasha selile guhindura ibiryo imbaraga (ATP). Byongeye kandi, NAD + ikora nka cofactor ikenewe kuri enzymes zitandukanye (nka PARP na Sirtuins), ikagira uruhare mubikorwa bijyanye no gusana ADN, ibimenyetso bya selile, no kurwanya gusaza.
Ni ubuhe bushakashatsi bwakozwe na NAD +?
Ibyingenzi byingenzi mubikorwa byinshi:
NAD + ni cofactor yingenzi mubikorwa byinshi bya redox (Shats I, 2020). Muri selile, igira uruhare mubikorwa byinshi bya selile nka metabolism yingufu, ituze rya genomic, hamwe nubudahangarwa bw'umubiri. Kurugero, muri metabolism yingufu, NAD + ikora nkitwara rya electron mubikorwa nka glycolysis na cycle tricarboxylic, ikagira uruhare muri redox reaction kugirango ihindure ingufu za chimique muntungamubiri nka glucose muburyo ingirabuzimafatizo zishobora gukoresha.
Imikoranire na Enzymes nyinshi:
NAD + kandi ikorana na enzymes nyinshi, nka ADN yo gusana enzyme poly- (adenosine diphosphate-ribose) polymerase (PARP), protein deacylase SIRTUINS, hamwe na ADP ribose enzyme ya CD38. Iyi misemburo igenga imikorere ya selile, nko gusana ADN, imvugo ya gene, no kugenzura ingirabuzimafatizo, ukoresheje NAD +.
Ni ubuhe buryo bwo gukora bwa NAD +?
Nka Coenzyme muri Redox reaction
Kubungabunga Cellular Redox Homeostasis:
'NAD ' mubisanzwe bivuga umugongo wimiti ya nicotinamide adenine dinucleotide, mugihe 'NAD + ' na 'NADH ' bivuga uburyo bwa okiside kandi bwagabanutse. NAD + igira uruhare runini mugucunga inzira nyinshi za biohimiki, kandi igipimo cya NAD + / NADH ningirakamaro mugukomeza selile redox homeostasis [1] . Indinganizo ya redox idasanzwe ningirakamaro kumikorere isanzwe ya selile, harimo ingufu za metabolisme, kurinda antioxydeant, nibindi. NAD + ikora nkuwakira electron cyangwa umuterankunga mubitekerezo bya redox, akagira uruhare mubikorwa byo kubyara ingufu zidasanzwe, nka acide ya tricarboxylic na fosifori ya okiside.
Kugenga Metabolism Ingufu:
NAD + igira uruhare mubikorwa byinshi byingufu za metabolism. Kurugero, muri glycolysis hamwe na tricarboxylic acide cycle, NAD + yemera atome ya hydrogen hanyuma ihinduka NADH. NADH noneho yohereza electron muri ogisijeni binyuze mumurongo wo gutwara electron kuri membrane imbere ya mitochondrial imbere kugirango ikore ATP. Igenamigambi ryingufu za metabolisme ningirakamaro mubuzima no gukora kwingirabuzimafatizo, cyane cyane mubice bifite imbaraga nyinshi nkumutima nubwonko [1].
Kwitabira Imyitozo ya Enzymatique
Uruhare hamwe na Poly (ADP-ribose) Polymerase 1 (PARP1):
NAD + ikora nka enzyme yunvikana cyangwa ikoresha enzyme ya PARP1 kandi igira uruhare mubikorwa byinshi byingenzi. PARP1 igira uruhare runini mugusana ibyangiritse kuri ADN. Iyo selile zangiritse kuri ADN, PARP1 irakora kandi ikoresha NAD + muguhuza iminyururu ya poly ADP-ribose (PAR), hanyuma igahuzwa na poroteyine, bityo igateza imbere gahunda yo gusana ADN. Nyamara, gukora cyane kwa PARP1 bizatwara NAD + nyinshi, biganisha ku kugabanuka kurwego rwimitsi ya NAD +, ari nako bigira ingaruka ku mbaraga za metabolism no kubaho kwingirabuzimafatizo [1, 2].
Uruhare hamwe na Cycle ADP-ribose (cADPR) Synthase:
Cycle ADP-ribose synthase nka CD38 na CD157 nayo NAD + ikoresha enzymes. Iyi misemburo ikoresha NAD + muguhuza cADPR. cADPR ikora nk'intumwa ya kabiri igira uruhare mu kwerekana ibimenyetso bya calcium, igenga intungamubiri za calcium ion, bityo bikagira ingaruka ku mikorere itandukanye ya selile, nko kugabanuka kw'imitsi no kurekura neurotransmitter.
Uruhare hamwe na Sirtuin Protein Deacetylase:
Sirtuin protein deacetylase (SIRTs) nayo yishingikiriza kuri NAD + kugirango ikore. SIRTs igenga imvugo ya gene, metabolisme selile, hamwe nibisubizo biterwa no guhagarika proteine. Kurwego rwo hejuru rwa NAD +, ibikorwa bya SIRTs byongerewe imbaraga, biteza imbere ubuzima no kubaho kwingirabuzimafatizo. Kurugero, mubihe nko kubuza calorie, urwego rudasanzwe rwa NAD + urwego rwiyongera, gukora SIRTs, bityo bikongerera igihe cyo kubaho no kuzamura ubuzima bwa metabolike [2].
Uruhare muri Axonal Degeneration
Imikoranire hagati ya NMNAT2 na SARM1:
Mugihe cyo kwangirika kwa axon, synthase NAD + synthase NMNAT2 hamwe na pro-degeneration SARM1 igira uruhare runini. NMNAT2 nikintu cyo kubaho cya axonal, mugihe SARM1 ifite NADase nibikorwa bifitanye isano kandi ni ibintu byangiza. Imikoranire hagati yombi ningirakamaro mu gukomeza ubusugire bwa axon. Mubihe byinshi, kwangirika kwa axon guterwa ninzira yo hagati yerekana inzira, igengwa cyane na proteine zombi zingenzi zifite ingaruka zinyuranye. Kurugero, mu ndwara zifata ubwonko nkindwara ya Alzheimer nindwara ya Parkinson, axon yangirika mbere yurupfu rwimibiri ya selile, kandi uku kwangirika kwa axon kugaragara no mubikomere bya axon nka heredita spast paraplegia. Muri izo ndwara, gukora iyi nzira yerekana ibimenyetso bishobora gutera impinduka za axon [3, 4].
Uburyo bwa NAD + -guhuza uburyo bwo Kwibuza SARM1:
Ubushakashatsi bwerekanye ko NAD + ari ligand itunguranye kuri armadillo / ubushyuhe bwo gusubiramo motifs (ARM) ya SARM1. Guhuza NAD + kuri domaine ya ARM ibuza ibikorwa bya NADase ya Toll / interleukin-1 reseptor (TIR) ya SARM1 ikoresheje interineti. Guhagarika urubuga NAD + guhuza cyangwa imikoranire ya ARM-TIR bizaganisha kumikorere ya SARM1, bivamo kwangirika kwa axon. Ibi byerekana ko NAD + ihuza kwifata kwi poroteyine ya neurodegenerative [5].
Uruhare mu ndwara zifata umutima
Kurinda ubuzima bwumutima nimiyoboro:
NAD + igira ingaruka zo gukingira indwara zifata umutima. Kurugero, NAD + irashobora kurinda umutima indwara nka syndrome de metabolike, kunanirwa k'umutima, gukomeretsa ischemia-reperfusion, arththmia, na hypertension. Uburyo bwayo bwo kurinda bushobora kuba bukubiyemo ibintu byinshi nko kugenzura ingufu za metabolisme, gukomeza kuringaniza redox, no guhagarika igisubizo. Hamwe no gusaza cyangwa guhangayika, urwego rudasanzwe rwa NAD + rugabanuka, biganisha kumihindagurikire yimiterere ya metabolike no kongera kwandura indwara. Kubwibyo, kugumana urwego rwa NAD + mumutima cyangwa kugabanya igihombo ni ngombwa kubuzima bwumutima nimiyoboro y'amaraso [1].
Uruhare mu Igituntu
Ingaruka kuri Mycobacterium igituntu (Mtb):
Muri Mycobacterium igituntu (Mtb), nyirabayazana w'igituntu, enzyme ya termin ya synthesis ya NAD, synthetase ya NAD (NadE), hamwe na enzyme ya terminal ya NADP biosynthesis, NAD kinase (PpnK), bigira ingaruka zitandukanye za metabolike na mikorobi. Kudakora kwa NadE biganisha ku kugabanuka kubangikanye n’ibidendezi bya NAD na NADP no kugabanuka kwubuzima bwa Mtb, mugihe kudakora kwa PpnK byatoranije guhitamo ikidendezi cya NADP ariko bigahagarika gukura gusa. Kudakora kwa buri misemburo biherekejwe nimpinduka za metabolike yihariye ya enzyme yibasiwe na mikorobe ifitanye isano. Urwego rwa bacteriostatike yo kugabanuka kwa NAD rushobora gutera impinduka zisubiramo inzira ya metabolike iterwa na NAD itagize ingaruka ku kigereranyo cya NADH / NAD, mugihe urugero rwa bagiteri ziterwa no kugabanuka kwa NAD rushobora guhungabanya igipimo cya NADH / NAD kandi bikabuza guhumeka umwuka wa ogisijeni. Ubu bushakashatsi bugaragaza umwihariko wa physiologique utaramenyekana bijyanye no gukenera cofactors ebyiri ziboneka mu bwihindurize, byerekana ko NAD biosynthesis inhibitor ikwiye gushyirwa imbere mugutezimbere imiti igabanya ubukana [6].
Uruhare rwo gusaza n'indwara
Kugabanuka muri Cellular NAD Urwego rujyanye no gusaza:
Hamwe no gusaza, urwego rwimitsi NAD + urwego rugabanuka buhoro buhoro. Uku kugabanuka kurwego rwa NAD + bifitanye isano nihinduka ryimiterere ya metabolike ya selile ishaje kandi irashobora kongera kwandura indwara. Indwara nyinshi z’indwara, harimo n'indwara z'umutima-damura, umubyibuho ukabije, indwara zifata ubwonko, kanseri, ndetse no gusaza, bifitanye isano no kwangirika ku buryo butaziguye cyangwa butaziguye urwego rwo mu nda rwa NAD + [2, 7].
Isano iri hagati ya NAD + Biosynthesis hamwe no gukoresha Enzymes n'indwara:
NAD + biosynthesis hamwe no gukoresha imisemburo bigira uruhare munzira nyinshi zingenzi zibinyabuzima, bigira ingaruka kumyandikire ya gene, ibimenyetso bya selile, no kugenzura ingirabuzimafatizo. Kubwibyo, indwara nyinshi zifitanye isano nimikorere idasanzwe yiyi misemburo. Kurugero, mu ndwara zifata ubwonko, uburyo bwa NAD + -bwigenga bushingiye kuri poroteyine nka WLDs, NMNAT2, na SARM1, byerekana ko indwara zifata ubwonko zifitanye isano na NAD + na metabolism y'ingufu [4]
Inkomoko: Byatangajwe [7]
Ni ubuhe buryo bwo gusaba bwa NAD +?
Gushyira mu bikorwa Indwara z'umutima
Ingaruka zo Kurinda:
NAD + igira uruhare runini mu ndwara zifata umutima, kandi irashobora kurinda umutima indwara zitandukanye. Kurugero, NAD + irashobora kurinda umutima indwara nka syndrome de metabolike, kunanirwa k'umutima, gukomeretsa ischemia-reperfusion, arththmia, na hypertension [1] . Ni ukubera ko NAD + ikora nka enzyme yunvikana cyangwa ikoresha imisemburo ya enzymes nka poly (ADP-ribose) polymerase 1 (PARP1), synthase ya ADP-ribose (cADPR) synthase (CD38 na CD157), na sirtuin protein deacetylase (Sirtuins, SIRTs), kandi igira uruhare mubikorwa byinshi byingenzi byumutima.
Kugumana uburimbane bwa Redox:
Ikigereranyo cya NAD + / NADH ni ingenzi mu kubungabunga redox homeostasis ya selile no kugenzura ingufu za metabolism [1] . Kubwibyo, kugumana urwego rwa NAD + mumutima cyangwa kugabanya igihombo ni ngombwa kubuzima bwumutima.
Porogaramu muri Anti-gusaza
Kwagura Ubuzima:
Impamvu zitera gusaza kwa molekile no kuramba byagaragaye ko byiyongereye mumyaka icumi ishize. Nikotinamide adenine dinucleotide (NAD) hamwe nabayibanjirije, nka nicotinamide riboside, nicotinamide mononucleotide, nicotinamide, na acide nicotinic, byashimishije abantu nka molekile zishimishije mugukoresha molekile ntoya nka geroprotector na / cyangwa farumasi. Izi nteruro zerekanye ko zishobora guteza imbere gusaza nyuma yo kuzuzwa kandi zishobora gukumira urupfu rw’ibinyabuzima by’icyitegererezo [8].
Guhindura Amabwiriza Yubuzima Bwose:
Mu binyabuzima byintangarugero nkumusemburo, ubushakashatsi bwerekanye ko abambere NAD bafite uruhare runini mugusaza no kuramba. Binyuze mu bushakashatsi bwigihe cyigihe (CLS) hamwe nigihe cyo kubaho (RLS) cyumusemburo, dushobora gusobanukirwa neza nuburyo bwa metabolism ya NAD ninshingano zayo mugusaza no kuramba [8].
Ibishoboka Mubishobora Kuvura Igituntu
Intego yibiyobyabwenge:
Kudakora kwa enzyme ya terminal ya synthesis ya NAD, synthetase ya NAD (NadE), muri Mycobacterium tuberculose (Mtb) itera kugabanuka kuburinganire bwibidendezi bya NAD na NADP no kugabanuka kwubuzima bwa Mtb, mugihe kudakora enzyme ya terminal ya NADP biosynthesis, NAD kinase (PpnK), guhitamo NAD kinase (PpnK) 2023). Ibi byerekana ko inhibitori ya NAD ifite umwanya wambere mugutezimbere imiti irwanya igituntu, kubera ko kubura NAD ari bagiteri, mugihe kubura NADP ari bacteriostatike.
Impinduka za metabolike na mikorobe ya mikorobe:
Kudakora kwa buri enzyme biherekejwe nimpinduka za metabolike yihariye ya enzyme yibasiwe na mikorobe ifitanye isano. Urwego rwa bacteriostatike yo kugabanuka kwa NAD rutera indishyi zisubiramo inzira ya metabolike iterwa na NAD itagize ingaruka ku kigereranyo cya NADH / NAD, mugihe urugero rwa bagiteri yica NAD itera guhagarika ihungabana rya NADH / NAD no kubuza umwuka wa ogisijeni [6].
Uruhare muri Metabolism ya Cellular
Imikorere myinshi y'ingenzi:
NAD (H) na NADP (H) basanzwe bafatwa nka cofactors zigira uruhare muri redox zitabarika, harimo no kohereza electron muri mitochondria. Nyamara, inzira ya metabolite ya NAD ifite indi mirimo myinshi yingenzi, harimo uruhare mukumenyesha inzira, guhindura nyuma yubusobanuro, guhindura epigenetike, no kugenzura imiterere ya RNA n'imikorere binyuze muri NAD ifata RNA [9].
Imikorere ya Metabolic Dynamic:
Imyitwarire idahwitse amaherezo iganisha kuri net catabolisme ya nucleotide, byerekana ko metabolism ya NAD ari inzira ikomeye cyane. Mubyukuri, ubushakashatsi buherutse kwerekana bwerekana ko mubice bimwe, igice cya kabiri cyubuzima bwa NAD ari iminota mike [9].
Uruhare muri Biologiya selile
Indwara idasanzwe ya NAD Metabolism:
NAD idasanzwe ni urufunguzo rwerekana molekile mubihe bitandukanye bya physiologique na patologi. Ikora mu buryo butaziguye ikora reseptor yihariye ya purinergique cyangwa mu buryo butaziguye nka substrate ya exonuclease (nka CD73, nucleotide pyrophosphatase / phosphodiesterase 1, CD38 na paralog yayo CD157, na ecto-ADP-ribosyltransferase). Iyi misemburo igena kuboneka kwa NAD idasanzwe idasanzwe ya hydrolyzing NAD, bityo igenga ingaruka zayo zerekana (Gasparrini M, 2021). Byongeye kandi, zirashobora kubyara molekile ntoya yerekana ibimenyetso biva muri NAD, nka adenosine ikingira immunomodulator, cyangwa gukoresha NAD kuri ADP-ribosylate proteine zitandukanye zidasanzwe na reseptor ya membrane, bigira ingaruka zikomeye mukurinda indwara, igisubizo kibabaza, tumorigenez, nizindi ndwara. Ibidukikije bidasanzwe kandi birimo nicotinamide fosiforiibosyltransferase na nicotinic aside fosiforiibosyltransferase, itanga ibisubizo byingenzi mumihanda ya salvage ya NAD idasanzwe. Imiterere idasanzwe y'iyi misemburo ikora nka cytokine ifite ibikorwa byo gutwika ibintu [10].
Mu gusoza, NAD + yabaye molekile yingenzi ihuza ubuzima nindwara muguhindura metabolism yingufu, gutinda gusaza, kugenzura ubudahangarwa, no gutanga uburinzi kuri sisitemu nyinshi. Kuzuza abayibanjirije birashobora kunoza imikorere ya mito-iyambere kandi bikadindiza iterambere ryindwara ziterwa na metabolike na neurodegenerative. Irerekana ubushobozi mubice byo kurinda umutima nimiyoboro y'amaraso, kurwanya kwandura, no kurwanya gusaza, bitanga intego zo kuvura indwara ziterwa no gusaza.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Jiang YF ni umushakashatsi ufitanye isano n’ibigo byinshi bizwi cyane, birimo kaminuza ya Peking, kaminuza ya Lanzhou Jiaotong, ikigo cy’ubushakashatsi bw’ubushakashatsi n’ikoranabuhanga mu kigo cy’igihugu ndetse n’ibanze, Ikigo cy’ubushakashatsi cy’ubushakashatsi bw’ikoranabuhanga cya Beijing, Ishuri Rikuru ry’Ubumenyi n’ikoranabuhanga rya (CAS), Ishuri Rikuru ry’Ubumenyi n’ikoranabuhanga rya kaminuza (CAS), Ishuri Rikuru ry’Ubumenyi n’ikoranabuhanga rya kaminuza, na kaminuza y’ubuvuzi. Ubushakashatsi bwe bwibanze ku bumenyi butandukanye, nka chimie, patologiya, injeniyeri, oncologiya, na acoustics. Ibikorwa bye byerekana inzira zinyuranye, zihuza iterambere ryubumenyi nikoranabuhanga murwego rumwe. Jiang YF yashyizwe ku rutonde rw'ibisobanuro [5].
