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1 kits (10 Vials)
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▎ NAD＋ Tsarin
Source: PubChem |
Jerin: N/A Tsarin kwayoyin halitta: C 21H 27N 7O 14P2 Nauyin Kwayoyin: 663.4 g/mol Lambar CAS: 53-84-9 Takardar bayanai:5892 Synonyms: nadide;coenzyme I;beta-NAD;Codehydrogenase I |
▎ NAD＋ Bincike
Menene NAD+?
NAD + (Nicotinamide Adenine Dinucleotide) wani muhimmin coenzyme ne wanda ke yaduwa a cikin halittu masu rai. An kafa shi ta hanyar haɗin adenosine ribonucleotide da nicotinamide ribonucleotide ta hanyar ƙungiyar phosphate. A matsayin babban coenzyme a cikin halayen redox, NAD + yana taka muhimmiyar rawa a cikin metabolism na salula. Yana iya canzawa tsakanin yanayin oxidized (NAD +) da jihar da aka rage (NADH), shiga cikin matakan makamashi na makamashi kamar glycolysis, da citric acid sake zagayowar, da kuma oxidative phosphorylation, taimaka sel canza abinci zuwa makamashi (ATP). Bugu da ƙari, NAD + yana aiki a matsayin mai mahimmanci mai mahimmanci don nau'o'in enzymes (irin su PARP da Sirtuins), shiga cikin matakai masu dangantaka da gyaran DNA, siginar salula, da kuma tsufa.
Menene asalin bincike na NAD+?
Muhimman Cofactor a cikin Maɗaukaki Maɗaukaki:
NAD + shine mahimmin cofactor a cikin halayen redox da yawa (Shats I, 2020). A cikin sel, yana da hannu a yawancin hanyoyin salula irin su makamashin makamashi, kwanciyar hankali na kwayoyin halitta, da amsawar rigakafi. Misali, a cikin metabolism na makamashi, NAD + yana aiki azaman mai ɗaukar lantarki a cikin matakai kamar glycolysis da zagayowar tricarboxylic acid, suna shiga cikin halayen redox don canza makamashin sinadarai a cikin abubuwan gina jiki kamar glucose zuwa nau'in makamashi wanda sel zasu iya amfani da su.
Yin hulɗa tare da Multiple Enzymes:
NAD + kuma yana hulɗa tare da enzymes da yawa, kamar DNA gyara enzyme poly- (adenosine diphosphate-ribose) polymerase (PARP), furotin deacylase SIRTUINS, da cyclic ADP ribose enzyme CD38. Waɗannan enzymes suna tsara hanyoyin salon salula, kamar gyaran DNA, bayyanar da kwayoyin halitta, da tsarin sake zagayowar tantanin halitta, ta hanyar cinye NAD +.
Menene tsarin aikin NAD+?
A matsayin Coenzyme a cikin Redox Reactions
Kula da Salon Redox Homeostasis:
'NAD' yawanci yana nufin kashin bayan sinadari na nicotinamide adenine dinucleotide, yayin da 'NAD+' da 'NADH' ke nufin sifofinsa masu oxidized da raguwa, bi da bi. NAD + yana taka muhimmiyar rawa wajen sarrafa yawancin hanyoyin sarrafa kwayoyin halitta, kuma rabon NAD +/NADH yana da mahimmanci don kiyaye redox homeostasis na salula [1] . Ma'auni na redox na intracellular yana da mahimmanci ga ayyukan salula na yau da kullum, ciki har da makamashi na makamashi, kariya na antioxidant, da dai sauransu. NAD + yana aiki a matsayin mai karɓar electron ko mai ba da gudummawa a cikin halayen redox, shiga cikin tsarin samar da makamashi na ciki, irin su tricarboxylic acid cycle da oxidative phosphorylation.
Daidaita Metabolism na Makamashi:
NAD + yana shiga cikin matakai masu mahimmanci na makamashi na makamashi. Misali, a cikin glycolysis da zagayowar tricarboxylic acid, NAD+ tana karɓar atom ɗin hydrogen kuma an canza shi zuwa NADH. Sannan NADH tana tura electrons zuwa iskar oxygen ta hanyar sarkar sufurin lantarki akan membrane na mitochondrial na ciki don samar da ATP. Tsarin wannan metabolism na makamashi yana da mahimmanci don rayuwa da aikin sel, musamman a cikin kyallen takarda tare da buƙatun makamashi mai yawa kamar zuciya da ƙwaƙwalwa [1].
Kasancewa a cikin Ayyukan Enzymatic
Matsayin da Poly(ADP-ribose) Polymerase 1 (PARP1):
NAD+ yana aiki azaman ji ko cinye enzyme don PARP1 kuma yana shiga cikin matakai masu mahimmanci. PARP1 tana taka muhimmiyar rawa wajen gyara lalacewar DNA. Lokacin da kwayoyin halitta suka sami lalacewar DNA, ana kunna PARP1 kuma suna amfani da NAD + don haɗa sarƙoƙi na poly ADP-ribose (PAR), waɗanda aka haɗa su da sunadaran, don haka inganta tsarin gyaran DNA. Koyaya, kunnawa da yawa na PARP1 zai cinye adadin NAD + mai yawa, yana haifar da raguwa a cikin matakan NAD + na ciki, wanda hakan ke shafar metabolism na makamashi da yuwuwar sel [1, 2].
Matsayin da Cyclic ADP-ribose (cADPR) Synthases:
Cyclic ADP-ribose synthases kamar CD38 da CD157 suma NAD+ suna cinye enzymes. Waɗannan enzymes suna amfani da NAD + don haɗa cADPR. cADPR acts as a second messenger to participate in calcium signaling, regulating the intracellular calcium ion concentration, and thus affecting various cellular functions, such as muscle contraction and neurotransmitter release.
Matsayin Sirtuin Protein Deacetylases:
Sirtuin protein deacetylases (SIRTs) suma sun dogara da NAD+ don aiki. SIRTs suna daidaita maganganun kwayoyin halitta, salon salula, da martanin damuwa ta hanyar lalata lalatawar sunadaran. A manyan matakan NAD +, ana haɓaka ayyukan SIRTs, suna haɓaka lafiya da rayuwar sel. Misali, a karkashin yanayi kamar ƙuntatawa calorie, matakin NAD + na ciki yana ƙaruwa, yana kunna SIRTs, ta haka ƙara tsawon rayuwa da haɓaka lafiyar rayuwa [2].
Matsayin Axonal Degeneration
Ma'amala tsakanin NMNAT2 da SARM1:
A lokacin aiwatar da lalatawar axonal, NAD + synthase NMNAT2 da pro-degeneration factor SARM1 suna taka muhimmiyar rawa. NMNAT2 wani abu ne na rayuwa na axonal, yayin da SARM1 yana da NADAse da ayyukan da ke da alaƙa kuma yana da mahimmancin haɓakawa. Haɗin kai tsakanin su biyu yana da mahimmanci don kiyaye amincin axonal. A yawancin lokuta, lalatawar axonal yana haifar da hanyar sigina ta tsakiya, wanda galibi waɗannan sunadaran sunadaran maɓalli guda biyu ke daidaita su tare da sabanin tasiri. Alal misali, a cikin cututtukan da ke haifar da rashin jin daɗi kamar cutar Alzheimer da cutar Parkinson, axon yana raguwa kafin mutuwar kwayoyin halitta, kuma wannan rashin lafiyar axonal yana da yawa a cikin cututtuka na axonal irin su spastic paraplegia na gado. A cikin waɗannan cututtuka, kunna wannan hanyar sigina na iya haifar da canje-canjen pathological axonal [3, 4].
NAD + - Tsarin Hana Kai Tsaye na SARM1:
Nazarin sun gano cewa NAD + wani ligand ne wanda ba a zata ba don yankin armadillo / zafi maimaita motifs (ARM) na SARM1. Haɗin NAD + zuwa yankin ARM yana hana ayyukan NADAse na Toll / interleukin-1 mai karɓa (TIR) na SARM1 ta hanyar haɗin yanki. Rushe wurin daurin NAD + ko hulɗar ARM-TIR zai haifar da ƙaddamar da ƙaddamarwa na SARM1, yana haifar da lalatawar axonal. Wannan yana nuna cewa NAD + tana yin sulhu don hana kai wannan sunadaran pro-neurodegenerative [5].
Matsayin da ke cikin Cututtukan Zuciya
Kare Lafiyar Zuciya:
NAD + yana da tasirin kariya a cikin cututtukan zuciya. Misali, NAD+ na iya kare zuciya daga cututtuka irin su ciwon zuciya, gazawar zuciya, raunin ischemia-reperfusion, arrhythmia, da hauhawar jini. Tsarin kariyar sa na iya haɗawa da abubuwa da yawa kamar daidaita tsarin makamashi, kiyaye ma'auni na redox, da hana amsawar kumburi. Tare da tsufa ko ƙarƙashin damuwa, matakin NAD + na intracellular yana raguwa, yana haifar da canje-canje a cikin yanayin rayuwa da haɓaka haɓakar cututtuka. Don haka, kiyaye matakin NAD + a cikin zuciya ko rage asarar sa yana da mahimmanci ga lafiyar zuciya [1].
Gudunmawar Tarin Fuka
Tasiri kan tarin fuka na Mycobacterium (Mtb):
A cikin Mycobacterium tarin fuka (Mtb), pathogen na tarin fuka, da m enzyme na NAD kira, NAD synthetase (NadE), da kuma m enzyme na NADP biosynthesis, NAD kinase (PpnK), da daban-daban na rayuwa da kuma microbiological effects. Rashin kunna NadE yana haifar da raguwa mai kama a cikin wuraren tafkunan NAD da NADP da raguwar yiwuwar Mtb, yayin da rashin kunna PpnK yana zaɓi ya lalata tafkin NADP amma yana dakatar da haɓaka. Rashin kunna kowane enzyme yana tare da sauye-sauye na rayuwa musamman ga enzyme da abin ya shafa da kuma nau'in kwayoyin halitta masu alaƙa. Matakan kwayoyin cuta na raguwar NAD na iya haifar da gyare-gyaren gyare-gyaren hanyoyin hanyoyin rayuwa na NAD ba tare da tasiri na NADH / NAD ba, yayin da matakan ƙwayoyin cuta na lalata NAD na iya rushe tsarin NADH / NAD kuma ya hana iskar oxygen. Waɗannan binciken sun bayyana ƙayyadaddun abubuwan da ba a san su ba a baya waɗanda ke da alaƙa da wajibcin masu haɗin gwiwar juyin halitta guda biyu, suna ba da shawarar cewa yakamata a ba da fifikon masu hana ƙwayoyin cuta na NAD a cikin haɓakar magungunan rigakafin tarin fuka [6].
Matsayin da ke cikin Tsufa da Cututtuka
Ragewa a Matakan NAD na salula masu alaƙa da tsufa:
Tare da tsufa, matakin NAD + na ciki a hankali yana raguwa. Wannan raguwa a matakin NAD + yana da alaƙa da canji a cikin yanayin rayuwa na ƙwayoyin tsufa kuma yana iya haɓaka kamuwa da cututtuka. Yawancin yanayin cututtukan cututtuka, gami da cututtukan zuciya na jijiyoyin jini, kiba, cututtukan neurodegenerative, ciwon daji, da tsufa, suna da alaƙa da lahani kai tsaye ko kai tsaye na matakan NAD + intracellular [2, 7].
Dangantaka tsakanin NAD+ Biosynthesis da Ciwon Enzymes da Cututtuka:
NAD + biosynthesis da cinyewar enzymes suna da hannu a cikin mahimman hanyoyin nazarin halittu da yawa, suna shafar rubutun kwayoyin halitta, siginar tantanin halitta, da tsarin sake zagayowar salula. Saboda haka, yawancin cututtuka suna da alaƙa da ayyukan da ba su da kyau na waɗannan enzymes. Misali, a cikin cututtukan neurodegenerative, hanyoyin da suka dogara da NAD + sun haɗa da sunadaran kamar WLDs, NMNAT2, da SARM1, yana nuna cewa cututtukan neurodegenerative suna da alaƙa da NAD + da metabolism na makamashi [4]
Source:PubMed [7]
Menene filayen aikace-aikacen NAD+?
Aikace-aikace a cikin Cututtukan Zuciya
Tasirin Kariya:
NAD+ yana taka muhimmiyar rawa a cututtukan zuciya, kuma yana iya kare zuciya daga cututtuka iri-iri. Alal misali, NAD + na iya kare zuciya daga cututtuka irin su ciwo na rayuwa, raunin zuciya, raunin ischemia-reperfusion, arrhythmia, da hauhawar jini [1] . Wannan saboda NAD + yana aiki azaman ji ko cinyewa enzymes don enzymes kamar poly (ADP-ribose) polymerase 1 (PARP1), cyclic ADP-ribose (cADPR) synthases (CD38 da CD157), da sirtuin protein deacetylases (Sirtuins, SIRTs), kuma yana shiga cikin manyan hanyoyin tafiyar matakai a cikin cututtukan zuciya.
Kula da Ma'auni na Redox:
Matsakaicin NAD +/NADH yana da mahimmanci don kiyaye redox homeostasis na sel da daidaita metabolism makamashi [1] . Don haka, kiyaye matakin NAD + a cikin zuciya ko rage asarar sa yana da mahimmanci ga lafiyar zuciya.
Aikace-aikace a cikin Anti-tsufa
Tsawaita Rayuwa:
Abubuwan da ke haifar da tsufa na kwayoyin halitta da kuma tsawon lokaci sun shaida karuwa a cikin shekaru goma da suka gabata. Nicotinamide adenine dinucleotide (NAD) da magabatan sa, irin su nicotinamide riboside, nicotinamide mononucleotide, nicotinamide, da nicotinic acid, sun jawo sha'awa a matsayin yuwuwar kwayoyin halitta masu ban sha'awa a cikin aikace-aikacen ƙananan ƙwayoyin cuta a matsayin m geroprotectors da / ko pharmacogenomics. Wadannan mahadi sun nuna cewa za su iya inganta yanayin da suka shafi tsufa bayan kari kuma suna iya hana mutuwar kwayoyin halitta [8].
Tasiri Dokokin Tsawon Rayuwa:
A cikin kwayoyin halitta irin su yisti, bincike ya nuna cewa masu gabatar da NAD suna taka muhimmiyar rawa wajen tsufa da tsawon rai. Ta hanyar nazarin tsawon rayuwa na lokaci-lokaci (CLS) da tsawon rayuwa (RLS) na yisti, za mu iya fahimtar tsarin NAD metabolism da rawar da yake takawa a cikin tsufa da tsawon rai [8].
Yiwuwar Aikace-aikace a cikin Maganin Tuberculosis
Manufar Drug:
Rashin kunna enzyme m na NAD kira, NAD synthetase (NadE), a cikin Mycobacterium tarin fuka (Mtb) yana haifar da raguwa mai daidaituwa a cikin wuraren waha na NAD da NADP da kuma raguwa a cikin yiwuwar Mtb, yayin da rashin kunnawa na m enzyme na NADP biosynthesis, NAD kinases kawai tasha Ppnple Pools (Ply depnple). (Sharma R, 2023). Wannan yana nuna cewa masu hana haɗakarwar NAD suna da fifiko a cikin haɓakar magungunan rigakafin tarin fuka, saboda ƙarancin NAD ƙwayoyin cuta ne, yayin da ƙarancin NADP shine bacteriostatic.
Canje-canje na Metabolic da Nau'in Halitta na Ƙanyoyin Halitta:
Rashin kunna kowane enzyme yana tare da sauye-sauye na rayuwa musamman ga enzyme da abin ya shafa da kuma nau'in phenotype na ƙananan ƙwayoyin cuta. Matakan kwayoyin cuta na raguwar NAD suna haifar da gyare-gyaren gyare-gyaren hanyoyin hanyoyin rayuwa na NAD ba tare da shafar rabon NADH / NAD ba, yayin da matakan ƙwayoyin cuta na raguwar NAD suna haifar da rushewar rabon NADH / NAD da hana iskar oxygen [6].
Rawar da ke cikin Halin Halitta
Ayyuka masu Muhimmanci da yawa:
NAD(H) da NADP(H) a al'adance ana ɗaukarsu a matsayin masu haɗin gwiwa da ke da hannu cikin halayen redox marasa adadi, gami da canja wurin lantarki a cikin mitochondria. Koyaya, metabolites na hanyar NAD suna da wasu mahimman ayyuka da yawa, gami da matsayi a cikin hanyoyin sigina, gyare-gyaren bayan fassarori, canje-canjen epigenetic, da daidaita daidaiton RNA da aiki ta hanyar NAD capping na RNA [9].
Tsari Mai Sauƙi:
Abubuwan da ba su da iskar oxygen a ƙarshe suna haifar da net catabolism na waɗannan nucleotides, yana nuna cewa NAD metabolism tsari ne mai ƙarfi sosai. A zahiri, binciken kwanan nan ya nuna a sarari cewa a cikin wasu kyallen takarda, rabin rayuwar NAD kusan mintuna kaɗan ne [9].
Gudunmawar Halittar Halitta
Extracellular NAD Metabolism:
Extracellular NAD shine mabuɗin siginar kwayoyin halitta a ƙarƙashin yanayi daban-daban na physiological da pathological. Yana aiki kai tsaye ta hanyar kunna takamaiman masu karɓa na purinergic ko a kaikaice azaman maɓalli don exonucleases (kamar CD73, nucleotide pyrophosphatase / phosphodiesterase 1, CD38 da paralog CD157, da ecto-ADP-ribosyltransferases). Wadannan enzymes suna ƙayyade samuwa na NAD na waje ta hanyar hydrolyzing NAD, don haka yana daidaita tasirin siginar sa kai tsaye (Gasparrini M, 2021). Bugu da ƙari, za su iya haifar da ƙananan ƙwayoyin sigina daga NAD, irin su adenosine na immunomodulator, ko amfani da NAD zuwa ADP-ribosylate daban-daban sunadaran sunadarai da masu karɓa na membrane, suna da tasiri mai mahimmanci akan tsarin rigakafi, amsawar kumburi, tumorigenesis, da sauran cututtuka. Yanayin extracellular shima ya ƙunshi nicotinamide phosphoribosyltransferase da nicotinic acid phosphoribosyltransferase, wanda ke haifar da halayen maɓalli a cikin hanyar ceton NAD ta cikin salula. Siffofin da ke waje na waɗannan enzymes suna aiki azaman cytokines tare da ayyuka masu kumburi [10].
A ƙarshe, NAD + ya zama maɓalli mai mahimmanci wanda ke haɗa lafiya da cuta ta hanyar daidaita ƙarfin kuzari, jinkirta tsufa, daidaita rigakafi, da ba da kariya ga tsarin da yawa. Haɓaka abubuwan da suka gabata na iya inganta aikin mitochondrial da rage jinkirin ci gaban cututtukan cututtukan da ke rayuwa da neurodegenerative. Yana nuna yuwuwar a cikin fagagen kariya na zuciya da jijiyoyin jini, rigakafin kamuwa da cuta, da rigakafin tsufa, yana ba da sabbin dabarun warkewa don cututtukan da ke da alaƙa da tsufa.
Game da Marubuci
Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.
Mawallafin Jaridar Kimiyya
Jiang YF wani mai bincike ne wanda ke da alaƙa da manyan cibiyoyi da yawa, ciki har da Jami'ar Peking, Jami'ar Lanzhou Jiaotong, Cibiyar Nazarin Haɗin gwiwar Injiniya ta ƙasa da na gida don Fasaha da aikace-aikace, Cibiyar Binciken Injiniya da Fasaha ta Beijing don Abubuwan Abincin Abinci, Kwalejin Kimiyya ta Sinawa, Jami'ar Kimiyya da Fasaha ta (CAS), Fasaha ta Beijing da Jami'ar Kasuwanci, da Jami'ar Kiwon Lafiya. Bincikensa ya shafi fannoni daban-daban, ciki har da sunadarai, ilimin cututtuka, injiniyanci, oncology, da acoustics. Ayyukansa suna nuna tsarin tsarin ilimi da yawa, yana haɗa ci gaban kimiyya da fasaha a cikin waɗannan fagage. An jera Jiang YF a cikin ambaton ambaton [5].
