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1 khoom (10Vials)
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▎ NAD ＋ Structure
Source: PubChem |
Sequence: N/A Molecular Formula: C 21H 27N 7O 14P2 Molecular Luj: 663.4 g / mol CAS Nr .: 53-84-9 Pub Chem CID: 5892 Synonyms: nadide; coenzyme I; beta-NAD; Codehydrogenase I |
▎ NAD + Kev Tshawb Fawb
NAD + yog dab tsi?
NAD + (Nicotinamide Adenine Dinucleotide) yog ib qho tseem ceeb coenzyme uas muaj nyob hauv cov kab mob muaj sia. Nws yog tsim los ntawm kev sib txuas ntawm adenosine ribonucleotide thiab nicotinamide ribonucleotide los ntawm ib pab pawg phosphate. Raws li cov tub ntxhais coenzyme hauv cov tshuaj tiv thaiv redox, NAD + ua lub luag haujlwm tseem ceeb hauv cellular metabolism. Nws tuaj yeem hloov pauv ntawm lub xeev oxidized (NAD +) thiab lub xeev txo (NADH), koom nrog cov txheej txheem ntawm lub zog metabolism xws li glycolysis, citric acid voj voog, thiab oxidative phosphorylation, pab cov hlwb hloov zaub mov rau hauv lub zog (ATP). Tsis tas li ntawd, NAD + ua haujlwm raws li qhov tsim nyog cofactor rau ntau yam enzymes (xws li PARP thiab Sirtuins), koom nrog cov txheej txheem cuam tshuam txog DNA kho, xov tooj ntawm tes, thiab tiv thaiv kev laus.
Dab tsi yog qhov kev tshawb fawb keeb kwm ntawm NAD +?
Qhov tseem ceeb Cofactor nyob rau hauv ntau yam Reactions:
NAD + yog ib qho tseem ceeb cofactor nyob rau hauv ntau yam redox tshuaj tiv thaiv (Shts I, 2020). Hauv cov hlwb, nws koom nrog ntau cov txheej txheem ntawm tes xws li lub zog metabolism, genomic stability, thiab kev tiv thaiv kab mob. Piv txwv li, hauv lub zog metabolism, NAD + ua raws li cov khoom siv hluav taws xob hauv cov txheej txheem xws li glycolysis thiab lub voj voog tricarboxylic acid, koom nrog cov tshuaj tiv thaiv redox los hloov cov tshuaj siv zog hauv cov khoom noj xws li qabzib mus rau hauv lub zog uas cov hlwb siv tau.
Kev sib cuam tshuam nrog ntau cov enzymes:
NAD + kuj cuam tshuam nrog ntau cov enzymes, xws li DNA kho enzyme poly-(adenosine diphosphate-ribose) polymerase (PARP), protein deacylase SIRTUINS, thiab cyclic ADP ribose enzyme CD38. Cov enzymes tswj cov txheej txheem ntawm tes, xws li kho DNA, kev qhia cov noob, thiab kev tswj lub voj voog ntawm tes, los ntawm kev noj NAD +.
Dab tsi yog qhov mechanism ntawm kev txiav txim ntawm NAD +?
Raws li Coenzyme hauv Redox Reactions
Txhim kho Cellular Redox Homeostasis:
'NAD' feem ntau yog hais txog cov tshuaj txha caj qaum ntawm nicotinamide adenine dinucleotide, thaum 'NAD +' thiab 'NADH' xa mus rau nws cov oxidized thiab txo cov ntaub ntawv, feem. NAD + ua lub luag haujlwm tseem ceeb hauv kev tswj hwm ntau cov txheej txheem biochemical, thiab NAD + / NADH piv yog qhov tseem ceeb rau kev tswj hwm cellular redox homeostasis [1] . Lub intracellular redox tshuav nyiaj li cas yog qhov tseem ceeb rau kev ua haujlwm ntawm tes, suav nrog lub zog metabolism, tiv thaiv antioxidant, thiab lwm yam NAD + ua raws li tus neeg txais hluav taws xob lossis tus neeg pub dawb hauv cov tshuaj tiv thaiv redox, koom nrog cov txheej txheem tsim hluav taws xob intracellular, xws li lub voj voog tricarboxylic acid thiab oxidative phosphorylation.
Regulating Zog Metabolism:
NAD + koom nrog ntau lub zog tseem ceeb ntawm cov txheej txheem metabolism. Piv txwv li, hauv glycolysis thiab tricarboxylic acid voj voog, NAD + lees txais hydrogen atoms thiab hloov mus rau NADH. NADH tom qab ntawd hloov cov hluav taws xob mus rau oxygen los ntawm cov khoom siv hluav taws xob thauj mus los ntawm cov khoom siv hauv mitochondrial los tsim ATP. Kev tswj hwm ntawm lub zog metabolism no yog qhov tseem ceeb rau kev ciaj sia thiab kev ua haujlwm ntawm cov hlwb, tshwj xeeb tshaj yog nyob rau hauv cov ntaub so ntswg uas xav tau lub zog siab xws li lub plawv thiab lub hlwb [1].
Kev koom tes hauv Enzymatic Reactions
Lub luag haujlwm nrog Poly (ADP-ribose) Polymerase 1 (PARP1):
NAD + ua raws li kev hnov mob lossis noj enzyme rau PARP1 thiab koom nrog ntau cov txheej txheem tseem ceeb. PARP1 ua lub luag haujlwm tseem ceeb hauv kev kho DNA puas. Thaum cov hlwb raug kev puas tsuaj DNA, PARP1 tau qhib thiab siv NAD + los ua ke cov saw hlau poly ADP-ribose (PAR), uas tom qab ntawd txuas rau cov protein, yog li txhawb cov txheej txheem kho DNA. Txawm li cas los xij, kev ua kom ntau dhau ntawm PARP1 yuav haus ntau ntau ntawm NAD +, ua rau txo qis hauv cov qib NAD +, uas ua rau muaj kev cuam tshuam rau lub zog metabolism thiab muaj peev xwm ntawm cov hlwb [1, 2].
Lub luag haujlwm nrog Cyclic ADP-ribose (cADPR) Synthases:
Cyclic ADP-ribose synthases xws li CD38 thiab CD157 kuj yog NAD + noj enzymes. Cov enzymes no siv NAD + los ua ke cADPR. cADPR ua raws li tus neeg xa xov thib ob los koom nrog hauv kev qhia txog calcium, tswj cov calcium ion concentration ntawm intracellular, thiab yog li cuam tshuam rau ntau yam cellular zog, xws li cov leeg nqaij contraction thiab neurotransmitter tso tawm.
Lub luag haujlwm nrog Sirtuin Protein Deacetylases:
Sirtuin protein deacetylases (SIRTs) kuj tso siab rau NAD + ua haujlwm. SIRTs tswj cov noob qhia, cellular metabolism, thiab kev ntxhov siab cov lus teb los ntawm catalyzing deacetylation ntawm cov proteins. Ntawm qib NAD + siab, kev ua haujlwm ntawm SIRTs tau txhim kho, txhawb kev noj qab haus huv thiab muaj sia nyob ntawm cov hlwb. Piv txwv li, nyob rau hauv tej yam kev mob xws li kev txwv calorie, lub intracellular NAD + qib nce, ua kom SIRTs, yog li ncua lifespan thiab txhim kho metabolic noj qab haus huv [2].
Lub luag haujlwm hauv Axonal Degeneration
Kev sib cuam tshuam ntawm NMNAT2 thiab SARM1:
Thaum lub sij hawm tus txheej txheem ntawm axonal degeneration, NAD + synthase NMNAT2 thiab pro-degeneration factor SARM1 ua lub luag haujlwm tseem ceeb. NMNAT2 yog qhov muaj sia nyob ntawm axonal, thaum SARM1 muaj NADase thiab lwm yam kev ua ub no thiab yog qhov ua rau tsis zoo. Kev sib cuam tshuam ntawm ob yog qhov tseem ceeb rau kev tswj hwm axonal kev ncaj ncees. Feem ntau, axonal degeneration yog tshwm sim los ntawm lub hauv paus teeb liab txoj hauv kev, uas yog tswj hwm los ntawm ob qho tseem ceeb ntawm cov proteins uas muaj qhov cuam tshuam. Piv txwv li, nyob rau hauv cov kab mob neurodegenerative xws li Alzheimer's kab mob thiab Parkinson's kab mob, axons degenerate ua ntej kev tuag ntawm neuronal cell lub cev, thiab axonal degeneration no kuj muaj nyob rau hauv axonal lesions xws li hereditary spastic paraplegia. Nyob rau hauv cov kab mob no, kev ua kom txoj kev taw qhia no yuav ua rau axonal pathological hloov [3, 4].
NAD +-Mediated Self-Inhibition Mechanism ntawm SARM1:
Kev tshawb fawb tau pom tias NAD + yog ib qho kev npaj txhij txog ligand rau armadillo / tshav kub rov motifs (ARM) ntawm SARM1. Kev khi ntawm NAD + mus rau ARM domain inhibits NADase kev ua haujlwm ntawm Tus Hu / interleukin-1 receptor (TIR) ntawm SARM1 los ntawm kev sib txuas lus. Kev cuam tshuam NAD + qhov chaw sib txuas lossis ARM-TIR kev sib cuam tshuam yuav ua rau muaj kev ua haujlwm ntawm SARM1, ua rau axonal degeneration. Qhov no qhia tau hais tias NAD + mediates tus kheej-inhibition ntawm no pro-neurodegenerative protein [5].
Lub luag haujlwm hauv Cov Kab Mob Ntshav Qab Zib
Kev tiv thaiv kab mob plawv:
NAD + muaj kev tiv thaiv kab mob plawv. Piv txwv li, NAD + tuaj yeem tiv thaiv lub plawv los ntawm cov kab mob xws li metabolic syndrome, plawv tsis ua haujlwm, ischemia-reperfusion raug mob, arrhythmia, thiab kub siab. Nws cov txheej txheem tiv thaiv tuaj yeem koom nrog ntau yam xws li tswj hwm lub zog metabolism, tswj kev sib npaug redox, thiab inhibiting cov lus teb inflammatory. Nrog rau kev laus los yog kev ntxhov siab, qhov intracellular NAD + qib txo qis, ua rau muaj kev hloov pauv hauv lub xeev metabolic thiab ua rau muaj kev cuam tshuam rau cov kab mob. Yog li ntawd, kev tswj hwm qib NAD + hauv plawv lossis txo nws txoj kev poob yog qhov tseem ceeb rau kev noj qab haus huv ntawm cov hlab plawv [1].
Lub luag haujlwm hauv Tuberculosis
Qhov cuam tshuam rau Mycobacterium tuberculosis (Mtb):
Hauv Mycobacterium tuberculosis (Mtb), cov kab mob ntawm tuberculosis, lub davhlau ya nyob twg enzyme ntawm NAD synthesis, NAD synthetase (NadE), thiab lub davhlau ya nyob twg enzyme ntawm NADP biosynthesis, NAD kinase (PpnK), muaj cov teebmeem metabolic thiab microbiological sib txawv. Kev tsis ua haujlwm ntawm NadE ua rau muaj qhov sib npaug ntawm NAD thiab NADP pas dej ua ke thiab kev poob qis hauv kev muaj peev xwm ntawm Mtb, thaum lub inactivation ntawm PpnK xaiv depletes NADP pas dej ua ke tab sis tsuas yog nres kev loj hlob. Lub inactivation ntawm txhua enzyme yog nrog los ntawm metabolic kev hloov tshwj xeeb rau cov cuam tshuam enzyme thiab lwm yam microbiological phenotype. Bacteriostatic qib ntawm NAD depletion tuaj yeem ua rau muaj kev hloov pauv ntawm NAD-nyob ntawm cov txheej txheem metabolic yam tsis muaj kev cuam tshuam rau NADH / NAD piv, thaum cov kab mob bactericidal ntawm NAD depletion tuaj yeem cuam tshuam NADH / NAD piv thiab inhibit oxygen ua pa. Cov kev tshawb pom no nthuav tawm yav dhau los tsis paub txog lub cev muaj feem cuam tshuam txog qhov tsim nyog ntawm ob lub evolutionarily ubiquitous cofactors, qhia tias NAD biosynthesis inhibitors yuav tsum tau ua ntej hauv kev txhim kho cov tshuaj tiv thaiv kab mob [6].
Lub luag haujlwm hauv Kev Laus thiab Kab Mob
Txo qis hauv Cellular NAD Qib ntsig txog Kev Laus:
Nrog rau kev laus, cov qib intracellular NAD + maj mam txo. Qhov kev txo qis hauv NAD + qib no cuam tshuam nrog kev hloov pauv hauv lub xeev metabolic ntawm cov hlwb laus thiab tuaj yeem ua rau muaj kev cuam tshuam rau cov kab mob. Ntau yam kab mob pathological, suav nrog cov kab mob plawv, rog rog, kab mob neurodegenerative, mob qog noj ntshav, thiab kev laus, muaj feem cuam tshuam rau kev cuam tshuam ncaj qha lossis tsis ncaj ntawm intracellular NAD + qib [2, 7].
Kev sib raug zoo ntawm NAD + Biosynthesis thiab Consuming Enzymes thiab Kab Mob:
NAD + biosynthesis thiab kev noj cov enzymes koom nrog ntau txoj hauv kev lom neeg, cuam tshuam rau cov noob qoob loo, kev taw qhia ntawm tes, thiab kev tswj xyuas lub voj voog ntawm tes. Yog li, ntau yam kab mob cuam tshuam nrog kev ua haujlwm txawv txav ntawm cov enzymes no. Piv txwv li, hauv cov kab mob neurodegenerative, NAD +-dependent mechanisms koom nrog cov proteins xws li WLDs, NMNAT2, thiab SARM1, qhia tias cov kab mob neurodegenerative muaj feem cuam tshuam nrog NAD + thiab lub zog metabolism [4]
Source: PubMed [7]
Dab tsi yog daim ntawv thov teb ntawm NAD +?
Kev siv hauv Cov Kab Mob Ntshav Qab Zib
Cov nyhuv tiv thaiv:
NAD + ua lub luag haujlwm tseem ceeb hauv cov kab mob plawv, thiab nws tuaj yeem tiv thaiv lub plawv los ntawm ntau yam kab mob. Piv txwv li, NAD + tuaj yeem tiv thaiv lub plawv los ntawm cov kab mob xws li metabolic syndrome, plawv tsis ua haujlwm, ischemia-reperfusion raug mob, arrhythmia, thiab kub siab [1] . Qhov no yog vim NAD + ua raws li kev hnov los yog siv cov enzymes xws li poly (ADP-ribose) polymerase 1 (PARP1), cyclic ADP-ribose (cADPR) synthases (CD38 thiab CD157), thiab sirtuin protein deacetylases (Sirtuins, SIRTs), thiab koom nrog ntau yam kab mob.
Txhim kho Redox Balance:
NAD + / NADH piv yog qhov tseem ceeb rau kev tswj hwm lub redox homeostasis ntawm cov hlwb thiab tswj lub zog metabolism [1] . Yog li ntawd, kev tswj hwm qib NAD + hauv plawv lossis txo nws txoj kev poob yog qhov tseem ceeb rau kev noj qab haus huv ntawm cov hlab plawv.
Daim ntawv thov hauv Anti-aging
Extending Lifespan:
Qhov ua rau kev laus molecular thiab kev cuam tshuam rau lub neej ntev tau pom muaj kev nce ntxiv hauv kaum xyoo dhau los. Nicotinamide adenine dinucleotide (NAD) thiab nws cov precursors, xws li nicotinamide riboside, nicotinamide mononucleotide, nicotinamide, thiab nicotinic acid, tau txais kev txaus siab raws li muaj peev xwm nthuav molecules nyob rau hauv daim ntawv thov ntawm me me molecules raws li muaj peev xwm geroprotectors thiab / los yog pharmaceuticals. Cov tebchaw no tau pom tias lawv tuaj yeem txhim kho kev laus ntawm cov xwm txheej tom qab ntxiv thiab tuaj yeem tiv thaiv kev tuag ntawm cov qauv kab mob [8].
Muaj feem cuam tshuam txog Txoj Cai Lij Choj:
Hauv cov qauv kab mob xws li cov poov xab, cov kev tshawb fawb tau pom tias NAD precursors ua lub luag haujlwm tseem ceeb hauv kev laus thiab kev ua neej ntev. Los ntawm txoj kev tshawb no ntawm chronological lifespan (CLS) thiab replicaative lifespan (RLS) ntawm poov xab, peb tuaj yeem nkag siab zoo txog cov txheej txheem ntawm NAD metabolism thiab nws txoj haujlwm tswj hwm hauv kev laus thiab kev ua neej ntev [8].
Muaj peev xwm siv tau rau hauv Kev Kho Mob Tuberculosis
Lub Hom Phiaj Tshuaj:
Lub inactivation ntawm lub davhlau ya nyob twg enzyme ntawm NAD synthesis, NAD synthetase (NadE), nyob rau hauv Mycobacterium tuberculosis (Mtb) ua rau ib qho kev txo qis hauv NAD thiab NADP pas dej ua ke thiab poob rau hauv kev muaj peev xwm ntawm Mtb, thaum lub inactivation ntawm lub davhlau ya nyob twg enzyme ntawm NADPs (NADPs) biosynthesis (NADPs). depletes lub pas dej NADP tab sis tsuas yog nres kev loj hlob (Sharma R, 2023). Qhov no qhia tau hais tias NAD synthesis inhibitors muaj qhov tseem ceeb hauv kev txhim kho cov tshuaj tiv thaiv kab mob, vim tias NAD tsis muaj cov kab mob bactericidal, thaum NADP tsis txaus yog bacteriostatic.
Metabolic Hloov thiab Microbial Phenotypes:
Lub inactivation ntawm txhua enzyme yog nrog los ntawm metabolic kev hloov tshwj xeeb rau cov cuam tshuam enzyme thiab lwm yam microbial phenotype. Bacteriostatic qib ntawm NAD depletion ua rau muaj kev hloov pauv ntawm NAD-raws li metabolic txoj hauv kev yam tsis muaj kev cuam tshuam rau NADH / NAD piv, thaum cov bactericidal theem ntawm NAD depletion ua rau muaj kev cuam tshuam ntawm NADH / NAD ratio thiab inhibition ntawm oxygen respiration [6].
Lub luag haujlwm hauv Cellular Metabolism
Muaj nuj nqi tseem ceeb:
NAD(H) thiab NADP(H) ib txwm raug suav hais tias yog cov cofactors koom nrog suav tsis txheeb redox cov tshuaj tiv thaiv, suav nrog kev hloov hluav taws xob hauv mitochondria. Txawm li cas los xij, NAD txoj hauv kev metabolites muaj ntau lwm yam tseem ceeb, suav nrog lub luag haujlwm hauv kev taw qhia txoj hauv kev, kev hloov pauv tom qab, kev hloov pauv ntawm epigenetic, thiab tswj RNA stability thiab ua haujlwm los ntawm NAD capping ntawm RNA [9].
Dynamic Metabolic Txheej Txheem:
Cov tshuaj tiv thaiv tsis yog oxidative thaum kawg ua rau cov catabolism ntawm cov nucleotides no, qhia tias NAD metabolism yog cov txheej txheem tsis tshua muaj zog. Qhov tseeb, kev tshawb fawb tsis ntev los no qhia meej tias hauv qee cov ntaub so ntswg, ib nrab-lub neej ntawm NAD yog li ob peb feeb [9].
Lub luag haujlwm hauv Cell Biology
Extracellular NAD Metabolism:
Extracellular NAD yog ib qho tseem ceeb taw qhia molecule nyob rau hauv txawv physiological thiab pathological mob. Nws ua ncaj qha los ntawm kev ua kom cov purinergic receptors los yog tsis ncaj qha raws li lub substrate rau exonucleases (xws li CD73, nucleotide pyrophosphatase / phosphodiesterase 1, CD38 thiab nws paralog CD157, thiab ecto-ADP-ribosyltransferases). Cov enzymes no txiav txim siab txog qhov muaj NAD extracellular los ntawm hydrolyzing NAD, yog li tswj nws cov kev taw qhia ncaj qha (Gasparrini M, 2021). Tsis tas li ntawd, lawv tuaj yeem tsim cov teeb liab me me los ntawm NAD, xws li immunomodulator adenosine, lossis siv NAD rau ADP-ribosylate ntau cov proteins thiab cov membrane receptors, muaj kev cuam tshuam loj rau kev tiv thaiv kab mob, cov lus teb inflammatory, tumorigenesis, thiab lwm yam kab mob. Ib puag ncig extracellular kuj muaj nicotinamide phosphoribosyltransferase thiab nicotinic acid phosphoribosyltransferase, uas catalyze cov tshuaj tiv thaiv tseem ceeb hauv NAD txoj kev cawm seej intracellularly. Cov ntaub ntawv extracellular ntawm cov enzymes ua raws li cytokines nrog pro-inflammatory zog [10].
Hauv kev xaus, NAD + tau dhau los ua qhov tseem ceeb ntawm kev sib txuas kev noj qab haus huv thiab kab mob los ntawm kev tswj hwm lub zog metabolism, ncua kev laus, tswj kev tiv thaiv kab mob, thiab muab kev tiv thaiv rau ntau lub cev. Ntxiv nws cov precursors tuaj yeem txhim kho mitochondrial muaj nuj nqi thiab ua kom qeeb ntawm kev loj hlob ntawm cov kab mob metabolic thiab neurodegenerative. Nws qhia tau hais tias muaj peev xwm hauv kev tiv thaiv kab mob plawv, tiv thaiv kab mob, thiab tiv thaiv kev laus, muab cov hom phiaj kho mob tshiab rau cov kab mob laus.
Hais Txog Tus Sau
Cov ntaub ntawv hais saum toj no yog txhua yam tshawb fawb, kho thiab sau los ntawm Cocer Peptides.
Scientific Journal Author
Jiang YF yog tus kws tshawb fawb koom nrog ntau lub tsev kawm muaj koob npe, suav nrog Peking University, Lanzhou Jiaotong University, National thiab Local Joint Engineering Research Center for Technology thiab Applications, Beijing Engineering thiab Technology Research Center for Food Additives, Suav Academy of Sciences, University of Science thiab Technology of (CAS), Beijing Technology thiab Business University, thiab Medical University. Nws txoj kev tshawb fawb nthuav dav ntau yam kev qhuab qhia, suav nrog chemistry, pathology, engineering, oncology, thiab acoustics. Nws txoj haujlwm qhia txog ntau txoj kev qhuab qhia, sib koom ua ke kev tshawb fawb thiab thev naus laus zis thoob plaws cov haujlwm no. Jiang YF tau teev nyob rau hauv qhov kev siv ntawm cov ntaub ntawv pov thawj [5].
