NAD + 500mg

▎ NAD Ọdịdị

Isi mmalite: PubChem

Usoro: N/A Ụdị ihe omimi: C 21H 27N 7O 14P2 Ibu ibu: 663.4 g/mol Nọmba CAS: 53-84-9 PubChem CID: 5892 Synonyms: nadide;coenzyme I;beta-NAD;Codehydrogenase I.

▎ NAD Nchọpụta

Kedu ihe bụ NAD+?

NAD + (Nicotinamide Adenine Dinucleotide) bụ coenzyme dị mkpa nke dị n'ime ihe ndị dị ndụ. Emebere ya site na njikọ nke adenosine ribonucleotide na nicotinamide ribonucleotide site na otu phosphate. Dị ka isi coenzyme na mmeghachi omume redox, NAD + na-arụ ọrụ dị mkpa na metabolism cellular. Ọ nwere ike ịtụgharị n'etiti steeti oxidized (NAD +) na steeti belatara (NADH), na-ekere òkè na usoro metabolism ike dị ka glycolysis, okirikiri citric acid, na phosphorylation oxidative, na-enyere mkpụrụ ndụ aka ịtụgharị nri n'ime ike (ATP). Na mgbakwunye, NAD + na-eje ozi dị ka onye na-arụkọ ọrụ dị mkpa maka enzymes dị iche iche (dị ka PARP na Sirtuins), na-ekere òkè na usoro metụtara nrụzi DNA, akara cell, na mgbochi ịka nká.

Kedu ihe ndabere nyocha nke NAD+?

Cofactor dị mkpa na mmeghachi omume ọtụtụ: 

NAD + bụ ihe nkwado dị mkpa na ọtụtụ mmeghachi omume redox (Shats I, 2020). N'ime sel, ọ na-etinye aka n'ọtụtụ usoro cellular dị ka metabolism ike, nkwụsi ike nke genomic, na nzaghachi mgbochi. Dịka ọmụmaatụ, na metabolism ike, NAD + na-arụ ọrụ dị ka onye na-ebu elektrọn na usoro dị ka glycolysis na usoro tricarboxylic acid, na-ekere òkè na mmeghachi omume redox iji gbanwee ike kemịkalụ na nri dị ka glucose ka ọ bụrụ ụdị ume nke mkpụrụ ndụ nwere ike iji.

Mmekọrịta ya na ọtụtụ enzymes: 

NAD + na-ejikọkwa ya na ọtụtụ enzymes, dị ka DNA mmezi enzyme poly- (adenosine diphosphate-ribose) polymerase (PARP), protein deacylase SIRTUINS, na cyclic ADP ribose enzyme CD38. Enzymes ndị a na-ahazi usoro cellular, dị ka nrụzi DNA, okwu mkpụrụ ndụ ihe nketa, na usoro okirikiri cell, site na iri NAD +.

Kedu usoro NAD + si arụ ọrụ?

Dị ka Coenzyme na Redox Reactions

Ịkwado Cellular Redox Homeostasis: 

'NAD' na-ezokarị aka na ọkpụkpụ azụ kemịkal nke nicotinamide adenine dinucleotide, ebe 'NAD+' na 'NADH' na-ezo aka n'ụdị oxidized na mbelata, n'otu n'otu. NAD + na-arụ ọrụ dị mkpa n'ịchịkwa ọtụtụ usoro biochemical, yana NAD +/ NADH ruru dị oke mkpa maka idowe cellular redox homeostasis ^[1] . Ntụle redox intracellular dị mkpa maka ọrụ cellular nkịtị, gụnyere ike metabolism ike, nchebe antioxidant, wdg NAD + na-eme dị ka onye na-anabata electron ma ọ bụ onye na-enye onyinye na mmeghachi omume redox, na-ekere òkè na mmepụta ume intracellular, dị ka usoro tricarboxylic acid na phosphorylation oxidative.

Na-achịkwa Metabolism Ike: 

NAD + na-etinye aka na ọtụtụ usoro metabolism ike. Dịka ọmụmaatụ, na glycolysis na okirikiri tricarboxylic acid, NAD + na-anabata atom hydrogen wee gbanwee ghọọ NADH. NADH na-ebufe eletrọn na oxygen site na yinye njem elektrọn na akpụkpọ ahụ mitochondrial dị n'ime iji mepụta ATP. Usoro nke metabolism ike a dị mkpa maka ịlanarị na ọrụ nke mkpụrụ ndụ, ọkachasị na anụ ahụ nwere nnukwu ume dị ka obi na ụbụrụ ^[1].

Isonye na mmeghachi omume Enzymatic

Ọrụ ya na Poly(ADP-ribose) Polymerase 1 (PARP1): 

NAD + na-arụ ọrụ dị ka ihe na-ahụ ma ọ bụ na-eri enzyme maka PARP1 ma na-etinye aka na ọtụtụ usoro igodo. PARP1 na-arụ ọrụ dị mkpa na nrụzi mmebi DNA. Mgbe mkpụrụ ndụ nwere mmebi DNA, PARP1 na-arụ ọrụ ma jiri NAD + mepụta ụdọ poly ADP-ribose (PAR), nke etinyere na protein, si otú a na-akwalite usoro nrụzi DNA. Agbanyeghị, ịgbalite PARP1 gabigara ókè ga-eri NAD + buru ibu, na-eduga mbelata ọkwa NAD + intracellular, nke n'aka nke ya na-emetụta metabolism ike na ike nke mkpụrụ ndụ ^{[1, 2].}.

Ọrụ na cyclic ADP-ribose (cADPR) Synthases: 

Cyclic ADP-ribose synthases dị ka CD38 na CD157 bụkwa NAD + na-eri enzymes. Enzymes ndị a na-eji NAD + mepụta cADPR. cADPR na-arụ ọrụ dị ka onye ozi nke abụọ iji sonye na mgbaàmà calcium, na-achịkwa mkpokọta calcium ion intracellular intracellular, ma si otú a na-emetụta ọrụ dị iche iche nke cellular, dị ka mkpirisi muscle na ntọhapụ nke neurotransmitter.

Ọrụ ya na Sirtuin Protein Deacetylases: 

Sirtuin protein deacetylases (SIRTs) na-adaberekwa na NAD+ ka ọ rụọ ọrụ. SIRT na-ahazi okwu mkpụrụ ndụ ihe nketa, metabolism cellular, na nzaghachi nrụgide site n'ịkwalite deacetylation nke protein. Na ọkwa NAD + dị elu, a na-eme ka ọrụ SIRT dịkwuo elu, na-akwalite ahụike na ndụ nke sel. Dịka ọmụmaatụ, n'okpuru ọnọdụ dịka mmachi calorie, ọkwa NAD + intracellular na-abawanye, na-arụ ọrụ SIRT, si otú a na-agbatị ndụ ndụ ma na-eme ka ahụ ike nke metabolic ^{[2] dịkwuo mma.}.

Ọrụ na Axonal Degeneration

Mmekọrịta dị n'etiti NMNAT2 na SARM1: 

N'oge usoro nke axonal degeneration, NAD + synthase NMNAT2 na pro-degeneration factor SARM1 na-arụ ọrụ dị mkpa. NMNAT2 bụ ihe na-adị ndụ axonal, ebe SARM1 nwere NADAse na ihe omume ndị metụtara ya ma bụrụ ihe na-eme ka ọ ghara ịda mbà. Mmekọrịta dị n'etiti ha abụọ dị mkpa maka ikwado iguzosi ike n'ezi ihe axonal. N'ọtụtụ ọnọdụ, axonal degeneration na-ebute site na ụzọ mgbama etiti, bụ nke a na-achịkwa nke isi protein abụọ a nwere mmetụta dị iche. Dịka ọmụmaatụ, na ọrịa neurodegenerative dị ka ọrịa Alzheimer na ọrịa Parkinson, axon na-emebi tupu ọnwụ nke cell neuronal, na mmebi axonal a na-ahụkarị na ọnya axonal dị ka spastic paraplegia eketa. N'ime ọrịa ndị a, ịgbalite ụzọ mgbaàmà a nwere ike iduga mgbanwe mgbanwe axonal ^{[3, 4].}.

Usoro NAD +-Mediated Self Inhibition Mechanism nke SARM1: 

Nnyocha achọpụtala na NAD + bụ ligand na-atụghị anya ya maka ngalaba armadillo / okpomọkụ na-emegharị motifs (ARM) nke SARM1. Njikọ nke NAD + na ngalaba ARM na-egbochi ọrụ NADAse nke Toll / interleukin-1 receptor (TIR) ​​ngalaba nke SARM1 site na interface ngalaba. Ịgbaghasị saịtị njikọ NAD + ma ọ bụ mmekọrịta ARM-TIR ga-eduga n'ịrụ ọrụ nke SARM1, na-ebute axonal degeneration. Nke a na-egosi na NAD + na-akwado mgbochi onwe nke protein pro-neurodegenerative a ^[5].

Ọrụ dị n'ọrịa obi

Ichekwa ahụike obi: 

NAD + nwere mmetụta nchebe na ọrịa obi. Dịka ọmụmaatụ, NAD + nwere ike ichebe obi site na ọrịa ndị dị ka ọrịa metabolic syndrome, nkụda mmụọ obi, mmerụ ahụ ischemia-reperfusion, arrhythmia, na ọbara mgbali elu. Usoro nchebe ya nwere ike ịgụnye akụkụ dị iche iche dị ka ịhazi metabolism ume, ịnọgide na-enwe nguzozi redox, na igbochi nzaghachi mkpali. Na ịka nká ma ọ bụ n'okpuru nrụgide, ọkwa NAD + intracellular na-ebelata, na-eduga na mgbanwe na steeti metabolic na ịbawanye ohere nke ọrịa. Ya mere, idobe ọkwa NAD + n'ime obi ma ọ bụ ibelata ọnwụ ya dị oke mkpa maka ahụike obi ^[1].

Ọrụ dị na ụkwara nta

Mmetụta dị na ụkwara nta Mycobacterium (Mtb): 

Na Mycobacterium ụkwara nta (Mtb), pathogen nke ụkwara nta, njedebe enzyme nke NAD njikọ, NAD synthetase (NadE), na njedebe enzyme nke NADP biosynthesis, NAD kinase (PpnK), nwere dị iche iche metabolic na microbiological mmetụta. Mwepu nke NadE na-eduga na mbelata n'otu n'otu na ọdọ mmiri NAD na NADP yana mbelata na ike nke Mtb, ebe mwepu nke PpnK na-ahọrọ na-emebi ọdọ mmiri NADP mana naanị na-akwụsị uto. Mwepu nke enzyme ọ bụla na-esonyere ya na mgbanwe metabolic kpọmkwem na enzyme emetụtara na phenotype microbiological metụtara ya. Bacteriostatic ọkwa nke NAD nbibi nwere ike ime ka nkwụghachi ụgwọ nke ụzọ metabolic na-adabere na NAD na-enweghị emetụta NADH / NAD ratio, ebe bactericidal ọkwa nke NAD depletion nwere ike imebi NADH / NAD ratio ma gbochie ikuku oxygen. Nchọpụta ndị a na-ekpughe nkọwa gbasara ahụike nke a na-amatabeghị na mbụ metụtara mkpa nke ndị na-emekọ ihe abụọ evolushọn na-agbasa, na-atụ aro na NAD biosynthesis inhibitors kwesịrị ibute ụzọ na mmepe nke ọgwụ mgbochi ụkwara nta ^[6]..

Ọrụ dị na ịka nká na ọrịa

Mbelata na ọkwa NAD cellular metụtara ịka nká: 

Site na ịka nká, ọkwa intracellular NAD + ji nwayọọ nwayọọ na-ebelata. Mbelata a na ọkwa NAD + metụtara mgbanwe na ọnọdụ metabolic nke sel ịka nká ma nwee ike ịbawanye ohere nke ọrịa. Ọtụtụ ọnọdụ ọrịa, gụnyere ọrịa obi vaskụla, oke ibu, ọrịa neurodegenerative, kansa, na ịka nká, metụtara mmerụ ahụ kpọmkwem ma ọ bụ na-apụtaghị ìhè nke ọkwa NAD + intracellular ^{[2, 7]}.

Mmekọrịta dị n'etiti NAD + Biosynthesis na iri Enzymes na Ọrịa: 

NAD + biosynthesis na enzymes iri nri na-etinye aka n'ọtụtụ ụzọ usoro ndu, na-emetụta ndenye mkpụrụ ndụ ihe nketa, akara mkpụrụ ndụ, yana ụkpụrụ okirikiri cell. Ya mere, ọtụtụ ọrịa na-emetụta ọrụ na-adịghị mma nke enzymes ndị a. Dịka ọmụmaatụ, na ọrịa neurodegenerative, usoro NAD + dabere na-agụnye protein dị ka WLDs, NMNAT2, na SARM1, na-egosi na ọrịa neurodegenerative metụtara NAD + na ike metabolism ^[4].

Isi mmalite: PubMed ^[7]

Kedu mpaghara ngwa NAD +?

Ngwa na Ọrịa obi

Mmetụta Nchedo: 

NAD + na-ekere òkè dị mkpa na ọrịa obi, ọ pụkwara ichebe obi pụọ n'ọrịa dị iche iche. Dịka ọmụmaatụ, NAD + nwere ike ichebe obi site na ọrịa ndị dị ka ọrịa metabolic syndrome, nkụda mmụọ obi, mmerụ ahụ ischemia-reperfusion, arrhythmia, na ọbara mgbali elu ^[1] . Nke a bụ n'ihi na NAD + na-eme dị ka ihe na-ahụ ma ọ bụ na-eri enzymes maka enzymes dị ka poly (ADP-ribose) polymerase 1 (PARP1), cyclic ADP-ribose (cADPR) synthases (CD38 na CD157), na sirtuin protein deacetylases (Sirtuins, SIRTs), na-etinye aka na ọtụtụ isi usoro na ọrịa obi.

Na-edobe Balance Redox: 

Ngụkọta NAD +/NADH dị oke mkpa maka idowe redox homeostasis nke sel na ịhazi metabolism ike ^[1] . Ya mere, idobe ọkwa NAD + n'ime obi ma ọ bụ ibelata ọnwụ ya dị oke mkpa maka ahụike obi.

Ngwa na mgbochi ịka nká

Na-agbatị ndụ: 

Ihe na-akpata ịka nká nke mkpụrụ ndụ ihe nketa na ntinye aka ogologo ndụ achọpụtala mmụba n'ime afọ iri gara aga. Nicotinamide adenine dinucleotide (NAD) na ihe mmalite ya, dị ka nicotinamide riboside, nicotinamide mononucleotide, nicotinamide, na nicotinic acid, adọtala mmasị dị ka ụmụ irighiri ihe ndị nwere mmasị na ntinye nke obere ụmụ irighiri ihe dị ka geroprotectors na/ma ọ bụ pharmacogenomics. Ogige ndị a egosila na ha nwere ike imeziwanye ọnọdụ ndị metụtara ịka nká mgbe emejuchara ya ma nwee ike igbochi ọnwụ nke ụdị ntule ^[8].

Na-emetụta Iwu Ogologo Ndụ: 

N'ime ụdị ụdị dị ka yist, ọmụmụ egosila na ndị na-ebu ụzọ NAD na-arụ ọrụ dị mkpa na ịka nká na ogologo ndụ. Site n'ọmụmụ nke oge ndụ oge (CLS) na ndụ replicative (RLS) nke yist, anyị nwere ike ịghọta nke ọma usoro nke NAD metabolism na ọrụ nchịkwa ya na ịka nká na ogologo ndụ ^[8].

Ngwa enwere ike na ọgwụgwọ ụkwara nta

Ebumnuche ọgwụ: 

Mwepu nke enzyme njedebe nke NAD synthetase, NAD synthetase (NadE), na Mycobacterium ụkwara nta (Mtb) na-eduga na mbelata n'otu ebe na ọdọ mmiri NAD na NADP na mbelata na viability nke Mtb, ebe inactivation nke njedebe enzyme nke NADP biosynthesis, NAD kinase, na-akwụsị na-ahọrọ naanị PAPnple ọdọ mmiri. (Sharma R, 2023). Nke a na-egosi na ndị na-egbochi NAD synthesis na-ebute ụzọ na mmepe nke ọgwụ mgbochi ụkwara nta, n'ihi na ụkọ NAD bụ nje bacteria, ebe ụkọ NADP bụ bacteriostatic.

Mgbanwe Metabolic na Phenotypes Microbial: 

Mwepu nke enzyme ọ bụla na-esonyere ya na mgbanwe metabolic kpọmkwem na enzyme emetụtara na phenotype microbial metụtara ya. Bacteriostatic ọkwa nke NAD nbibi na-akpata nkwụghachi ụgwọ nke ụzọ metabolic na-adabere na NAD na-enweghị emetụta usoro NADH / NAD, ebe bactericidal ọkwa nke NAD depletion na-eduga ná nkwụsị nke NADH / NAD ratio na mgbochi nke ikuku oxygen ^[6].

Ọrụ dị n'ime metabolism cellular

Ọtụtụ ọrụ dị mkpa: 

A na-ahụta NAD (H) na NADP (H) dị ka ndị na-etinye aka na mmeghachi omume redox na-enweghị atụ, gụnyere nnyefe elektrọn na mitochondria. Agbanyeghị, metabolites ụzọ NAD nwere ọtụtụ ọrụ ndị ọzọ dị mkpa, gụnyere ọrụ na ụzọ akara, mgbanwe ntụgharị okwu, mgbanwe epigenetic, yana ịhazi nkwụsi ike RNA na ọrụ site na NAD capping nke RNA ^[9].

Usoro Metabolic dị ike: 

Mmeghachi omume na-abụghị nke oxidative na-eduga na net catabolism nke nucleotides ndị a, na-egosi na metabolism NAD bụ usoro siri ike. N'ezie, nnyocha ndị na-adịbeghị anya na-egosi n'ụzọ doro anya na na ụfọdụ anụ ahụ, ọkara ndụ NAD bụ ihe dị ka nkeji ole na ole ^[9].

Ọrụ dị n'ime ihe ndị dị ndụ cell

Metabolism NAD nke mpụga cell: 

Extracellular NAD bụ mkpụrụ ndụ ihe na-egosi isi n'okpuru ọnọdụ physiological na pathological dị iche iche. Ọ na-eme ozugbo site na ịgbalite ndị na-anabata purinergic kpọmkwem ma ọ bụ na-apụtaghị ìhè dị ka mkpụrụ maka exonucleases (dị ka CD73, nucleotide pyrophosphatase/phosphodiesterase 1, CD38 na paralog CD157, na ecto-ADP-ribosyltransferases). Enzymes ndị a na-achọpụta na enwere NAD extracellular site na hydrolyzing NAD, si otú a na-achịkwa mmetụta akara ngosi ya kpọmkwem (Gasparrini M, 2021). Tụkwasị na nke ahụ, ha nwere ike ịmepụta obere ihe mgbaàmà sitere na NAD, dị ka immunomodulator adenosine, ma ọ bụ jiri NAD ka ADP-ribosylate dị iche iche na-edozi protein na ndị na-anabata akpụkpọ ahụ, na-enwe mmetụta dị ukwuu na nchịkwa mgbochi, nzaghachi mkpali, tumorigenesis, na ọrịa ndị ọzọ. Mpaghara extracellular nwekwara nicotinamide phosphoribosyltransferase na nicotinic acid phosphoribosyltransferase, nke na-eme ka mmeghachi omume dị mkpa na ụzọ mgbapụta NAD intracellular. Ụdị extracellular nke enzymes ndị a na-arụ ọrụ dị ka cytokines nwere ọrụ pro-inflammatory ^[10].

Na mmechi, NAD + abụrụla ihe dị mkpa nke na-ejikọ ahụike na ọrịa site na ịhazi metabolism ike, igbu oge ịka nká, na-achịkwa mgbochi na inye nchebe maka ọtụtụ sistemụ. Ịgbakwunye ihe mmalite ya nwere ike melite ọrụ mitochondrial ma belata ọganihu nke ọrịa metabolic na neurodegenerative. Ọ na-egosi ike na ngalaba nchebe obi, mgbochi ọrịa, na mgbochi ịka nká, na-enye ebumnuche ọgwụgwọ ọhụrụ maka ọrịa ndị metụtara ịka nká.

Banyere Onye dere ya

Ihe niile a kpọtụrụ aha n'elu bụ Cocer Peptides na-enyocha, dezie ma chịkọta ya.

Onye ode akwụkwọ akụkọ sayensị

Jiang YF bụ onye nyocha jikọtara ya na ọtụtụ ụlọ ọrụ ama ama, gụnyere Mahadum Peking, Mahadum Lanzhou Jiaotong, National na Local Joint Engineering Research Center for Technology and Applications, Beijing Engineering and Technology Research Center for Food Additives, the Chinese Academy of Sciences, the University of Science and Technology of (CAS), Beijing Technology and Business University, and Medical University. Nchọcha ya gbasara usoro mmụta dị iche iche, gụnyere kemistri, pathology, engineering, oncology, and acoustics. Ọrụ ya na-egosipụta ụzọ dị iche iche, na-ejikọta ọganihu sayensị na nkà na ụzụ n'ofe ndị a. Edepụtara Jiang YF na ntụaka ntụaka [5].

▎ Okwu ndị dị mkpa

[1] Lin Q, Zuo W, Liu Y, et al. NAD na ọrịa obi [J]. Clinica Chimica Acta, 2021,515:104-110.DOI:10.1016/j.cca.2021.01.012.

[2] Shats I, Li X. Bacteria na-akwalite nnabata NAD metabolism[J]. Ịka nká-Anyị, 2020,12(23):23425-23426.DOI:10.18632/ịka nká.104219.

[3] Hopkins EL, Gu W, Kobe B, et al. Usoro nrịbama NAD novel na Axon Degeneration na Mmekọrịta ya na Innate Immunity[J]. Ihu ihu na Molecular Biosciences, 2021,8.DOI:10.3389/fmolb.2021.703532.

[4] Cao Y, Wang Y, Yang J. NAD + na-adabere na usoro nke axon degeneration pathological. Cell Nghọta, 2022,1 (2):100019.DOI:10.1016/j.cellin.2022.100019.

[5] Jiang YF, Liu TT, Lee C, et al. Usoro NAD ⁺ -mediated nke na-egbochi onwe ya nke pro-neurodegenerative SARM1[J]. Ọdịdị, 2020,588(7839):658.DOI:10.1038/s41586-020-2862-z.

[6] Sharma R, Hartman TE, Beites T, et al. Ọrụ dị iche iche nke Metabolically NAD synthetase na NAD kinase na-akọwa ịdị mkpa nke NAD na NADP na ụkwara nta Mycobacterium [J]. Mbio, 2023,14 (4).DOI:10.1128/mbio.00340-23.

[7] Campagna R, Vignini A. NAD ⁺ Homeostasis na NAD ⁺ -Enweta Enzymes: Mmetụta maka Ahụike Vascular[J]. Antioxidants, 2023,12 (2).DOI:10.3390/antiox12020376.

[8] Odoh CK, Guo X, Arnone JT, et al. Ọrụ nke NAD na NAD na-ebute ụzọ na ogologo ndụ na mgbanwe ndụ ndụ na yist budding, Saccharomyces cerevisiae [J]. Biogerontology, 2022,23 (2): 169-199.DOI:10.1007/s10522-022-09958-x.

[9] Chini CCS, Zeidler JD, Kashyap S, et al. Echiche na-agbanwe na NAD ⁺ metabolism[J]. Cell metabolism, 2021,33 (6): 1076-1087.DOI:10.1016/j.cmet.2021.04.003.

[10] Gasparrini M, Sorci L, Raffaelli N. Enzymology nke extracellular NAD metabolism[J]. Science ndụ ndụ cellular na molecular, 2021,78(7):3317-3331.DOI:10.1007/s00018-020-03742-1.

Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.  

Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.