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1kits (Ebipipa 10) .
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▎ NAD + Enzimba
Ensibuko: PubChem |
Omutendera: N/A Ensengekera ya molekyu: C 21H 27N 7O 14P2 Obuzito bwa molekyu: 663.4 g/mol Ennamba ya CAS: 53-84-9 PubChem CID: 5892. Enkola y’okukuuma eddagala lino Ebigambo ebikwatagana: nadide;coenzyme I;beta-NAD;Codehydrogenase I |
▎ NAD + Okunoonyereza
NAD+ kye ki?
NAD+ (Nicotinamide Adenine Dinucleotide) ye coenzyme enkulu esangibwa nnyo mu biramu. Kikolebwa okuyungibwa kwa adenosine ribonucleotide ne nicotinamide ribonucleotide okuyita mu kibinja kya phosphate. Nga core coenzyme mu redox reactions, NAD+ ekola kinene mu cellular metabolism. Kisobola okukyusa wakati w’embeera ya oxidized (NAD+) n’embeera ekendeezeddwa (NADH), nga kyetaba mu nkola z’okukyusakyusa amaanyi nga glycolysis, citric acid cycle, ne oxidative phosphorylation, okuyamba obutoffaali okukyusa emmere mu maanyi (ATP). Okugatta ku ekyo, NAD+ ekola nga cofactor eyeetaagisa eri enzymes ez’enjawulo (nga PARP ne Sirtuins), nga zeetaba mu nkola ezikwata ku kuddaabiriza DNA, obubonero bw’obutoffaali, n’okulwanyisa okukaddiwa.
Ensibuko y’okunoonyereza eya NAD+ eri etya?
Essential Cofactor mu Reactions Ennyingi:
NAD+ ye cofactor enkulu mu nkola za redox eziwera (Shats I, 2020). Mu butoffaali, yeenyigira mu nkola nnyingi ez’obutoffaali nga okukyusakyusa amaanyi, okutebenkera kw’ensengekera y’obutonde (genomic stability), n’okuddamu kw’abaserikale b’omubiri. Okugeza, mu nkyukakyuka y’amasoboza, NAD+ ekola ng’ekitwala obusannyalazo mu nkola nga glycolysis ne tricarboxylic acid cycle, nga yeetaba mu nsengekera za redox okukyusa amasoboza g’eddagala mu biriisa nga glucose mu ngeri y’amasoboza obutoffaali gye busobola okukozesa.
Enkolagana ne Enziyiza Ennyingi:
NAD+ era ekwatagana n’enziyiza eziwera, gamba nga enziyiza y’okuddaabiriza DNA eya poly-(adenosine diphosphate-ribose) polymerase (PARP), puloteyina deacylase SIRTUINS, n’enziyiza ya ADP ribose eya cyclic CD38. Enziyiza zino zitereeza enkola z’obutoffaali, gamba ng’okuddaabiriza DNA, okulaga obuzaale, n’okulungamya enzirukanya y’obutoffaali, nga zikozesa NAD+.
Enkola y’okukola kwa NAD+ eri etya?
Nga Coenzyme mu Redox Reactions
Okukuuma obutoffaali bwa Redox Homeostasis:
'NAD' kitera okutegeeza omugongo gw'eddagala ogwa nicotinamide adenine dinucleotide, ate 'NAD+' ne 'NADH' kitegeeza ebika byayo ebifuuse oxidized n'ebikendeezeddwa, mu kulondako. NAD+ ekola kinene mu kufuga enkola nnyingi ez’obutonde, era omugerageranyo gwa NAD+/NADH mukulu nnyo mu kukuuma cellular redox homeostasis [1] . Bbalansi ya redox mu butoffaali yeetaagibwa nnyo mu mirimu gy’obutoffaali egya bulijjo, omuli okukyusakyusa amasoboza, okuziyiza antioxidant, n’ebirala NAD+ ekola ng’omukkiriza oba omugabi wa obusannyalazo mu nsengekera za redox, nga yeetaba mu nkola y’okufulumya amaanyi mu butoffaali, gamba nga enzirukanya ya asidi wa tricarboxylic ne oxidative phosphorylation.
Okulungamya Enkyukakyuka y’Amaaso:
NAD+ yeenyigira mu nkola eziwerako ezikulu ez’okukyusakyusa amaanyi. Okugeza, mu glycolysis ne tricarboxylic acid cycle, NAD+ ekkiriza atomu za haidrojeni era n’ekyusibwa n’efuuka NADH. NADH olwo ekyusa obusannyalazo okudda mu okisigyeni okuyita mu lujegere lw’okutambuza obusannyalazo ku luwuzi lwa mitochondrial olw’omunda okukola ATP. Okulungamya enkyukakyuka y’amasoboza gano kyetaagisa nnyo mu bulamu n’enkola y’obutoffaali naddala mu bitundu ebirina amaanyi amangi ng’omutima n’obwongo [1] ..
Okwetaba mu Nkola z’Enziyiza
Omulimu ne Poly(ADP-ribose) Polymerase 1 (PARP1):
NAD+ ekola nga enziyiza y’okuwulira oba enywa ku PARP1 era yeenyigira mu nkola ezikulu eziwera. PARP1 ekola kinene mu kuddaabiriza DNA okwonooneka. Obutoffaali bwe bufuna okwonooneka kwa DNA, PARP1 ekola era n’ekozesa NAD+ okukola enjegere za poly ADP-ribose (PAR), oluvannyuma ne zigattibwa ku puloteyina, bwe kityo ne kitumbula enkola y’okuddaabiriza DNA. Wabula, okukola okuyitiridde okwa PARP1 kujja kulya omuwendo omunene ogwa NAD+, ekivaamu okukendeera mu miwendo gya NAD+ mu butoffaali, nga kino nakyo kikosa enkyukakyuka y’amasoboza n’obulamu bw’obutoffaali [1, 2]..
Omulimu ne Cyclic ADP-ribose (cADPR) Synthases:
Cyclic ADP-ribose synthases nga CD38 ne CD157 nazo enzymes ezirya NAD+. Enziyiza zino zikozesa NAD+ okukola cADPR. cADPR ekola ng’omubaka owookubiri okwetaba mu bubonero bwa kalisiyamu, okulungamya obungi bwa kalisiyamu ion mu butoffaali, era bwe kityo n’ekosa emirimu egy’enjawulo egy’obutoffaali, gamba ng’okukonziba kw’ebinywa n’okufulumya obusimu obutambuza obusimu.
Omulimu ne Sirtuin Protein Deacetylases:
Sirtuin protein deacetylases (SIRTs) nazo zeesigamye ku NAD+ okukola. SIRTs zitereeza okulaga kw’obuzaale, enkyukakyuka y’obutoffaali, n’okuddamu kwa situleesi nga zikola deacetylation ya puloteyina. Ku mitendera gya NAD+ egya waggulu, emirimu gya SIRTs gyongerwako, okutumbula obulamu n’obulamu bw’obutoffaali. Okugeza, mu mbeera nga okuziyiza kalori, omutindo gwa NAD+ mu butoffaali gweyongera, ne gukola SIRTs, bwe kityo ne kyongera ku bulamu n’okulongoosa obulamu bw’enkyukakyuka y’emmere [2]..
Omulimu mu kuvunda kw’ebitundu by’omubiri (Axonal Degeneration).
Enkolagana wakati wa NMNAT2 ne SARM1:
Mu nkola y’okuvunda kw’obusimu obuyitibwa axonal degeneration, NAD+ synthase NMNAT2 ne pro-degeneration factor SARM1 zikola emirimu emikulu. NMNAT2 nsonga ya bulamu bwa axonal, ate SARM1 erina NADase n’emirimu egyekuusa ku nsonga eno era nsonga ya pro-degeneration. Enkolagana wakati w’ebintu bino byombi yeetaagibwa nnyo okukuuma obulungi bw’ebitundu by’omubiri (axon integrity). Mu mbeera nnyingi, okuvunda kw’ebitundu by’omubiri (axon degeneration) kuva ku kkubo ly’obubonero erya wakati, nga lino lisinga kufugibwa puloteyina zino ebbiri enkulu nga zirina ebikolwa eby’enjawulo. Okugeza, mu ndwadde ezikosa obusimu nga Alzheimer’s disease ne Parkinson’s disease, axons zivunda nga emibiri gy’obutoffaali bw’obusimu teginnafa, era okuvunda kuno okw’obusimu nakyo kya bulijjo mu biwundu by’obusimu nga hereditary spastic paraplegia. Mu ndwadde zino, okukola kw’ekkubo lino ery’obubonero kuyinza okuvaako enkyukakyuka mu bulwadde bwa axonal [3, 4]..
Enkola y’okweziyiza eya NAD+-Mediated eya SARM1:
Okunoonyereza kuzudde nti NAD+ ligandi etasuubirwa eri ekitundu kya armadillo/heat repeat motifs (ARM) ekya SARM1. Okusiba NAD+ ku kitundu kya ARM kiziyiza emirimu gya NADase egy’ekitundu kya Toll/interleukin-1 receptor (TIR) ekya SARM1 okuyita mu nsengekera y’ekitundu. Okutabangula ekifo ekisiba NAD+ oba enkolagana ya ARM-TIR kijja kuleeta okukola constitutive activation ya SARM1, ekivaamu okuvunda kw’ebitundu by’omubiri (axonal degeneration). Kino kiraga nti NAD+ etabaganya okweziyiza kwa puloteyina eno eyamba obusimu [5]..
Omulimu mu Endwadde z’emisuwa n’emisuwa
Okukuuma Obulamu bw'emisuwa n'emisuwa:
NAD+ erina ekikolwa eky’obukuumi mu ndwadde z’emisuwa. Okugeza, NAD+ esobola okukuuma omutima okuva ku ndwadde nga metabolic syndrome, omutima okulemererwa, ischemia-reperfusion injury, arrhythmi, ne puleesa. Enkola yaayo ey’obukuumi eyinza okuzingiramu ebintu ebingi nga okulungamya enkyukakyuka y’amasoboza, okukuuma bbalansi ya redox, n’okuziyiza okuddamu kw’okuzimba. Nga bakaddiye oba nga bali ku situleesi, omutindo gwa NAD+ mu butoffaali gukendeera, ekivaako enkyukakyuka mu mbeera y’okukyusakyusa emmere n’okwongera okukwatibwa endwadde. N’olwekyo, okukuuma omutindo gwa NAD+ mu mutima oba okukendeeza ku kufiirwa kwagwo kikulu nnyo eri obulamu bw’emisuwa n’emisuwa [1]..
Omulimu mu Kafuba
Enkola y’akafuba ka Mycobacterium (Mtb):
Mu Mycobacterium tuberculosis (Mtb), obuwuka obulwaza akafuba, enziyiza ey’enkomerero ey’okukola NAD, NAD synthetase (NadE), n’enziyiza ey’enkomerero ey’okukola NADP, NAD kinase (PpnK), birina ebikolwa eby’enjawulo mu nkyukakyuka y’emmere n’ebiramu ebitonotono. Okutakola kwa NadE kuleeta okukendeera okukwatagana mu bidiba bya NAD ne NADP n’okukendeera kw’obusobozi bwa Mtb, ate obutakola kwa PpnK mu ngeri elondamu kukendeeza ekidiba kya NADP naye ne kuyimiriza okukula kwokka. Okutakola kwa buli enziyiza kuwerekerwako enkyukakyuka mu nkyukakyuka mu mubiri ezikwata ku enziyiza ekoseddwa n’enkula y’ebiramu ebitonotono ebikwatagana nayo. Emiwendo gy’okukendeera kwa NAD egy’okuziyiza obuwuka giyinza okuleeta okuddamu okukola mu ngeri ey’okusasula amakubo g’enkyukakyuka mu mubiri egyesigama ku NAD awatali kukosa mugerageranyo gwa NADH/NAD, ate emiwendo gy’okukendeera kwa NAD egy’okutta obuwuka giyinza okutaataaganya omugerageranyo gwa NADH/NAD n’okuziyiza okussa kwa oxygen. Ebizuuliddwa bino biraga ebikwata ku mubiri ebitamanyiddwa emabegako ebikwatagana n’obwetaavu bw’ebintu bibiri ebikwatagana (cofactors) ebisangibwa buli wamu mu nkulaakulana, ekiraga nti ebiziyiza okukola obulamu bwa NAD birina okukulembezebwa mu kukola eddagala eriweweeza ku kafuba [6]..
Omulimu mu kukaddiwa n’endwadde
Okukendeera mu miwendo gya NAD mu butoffaali obukwatagana n’okukaddiwa:
Nga bakaddiye, omutindo gwa NAD+ mu butoffaali gukendeera mpolampola. Okukendeera kuno mu mutindo gwa NAD+ kwekuusa ku nkyukakyuka mu mbeera y’okukyusakyusa emmere y’obutoffaali obukaddiye era kuyinza okwongera ku buzibu bw’okukwatibwa endwadde. Embeera nnyingi ez’obulwadde, omuli endwadde z’emisuwa n’emisuwa, omugejjo, endwadde z’obusimu, kookolo, n’okukaddiwa, zikwatagana n’okukosebwa obutereevu oba obutatereevu kw’emiwendo gya NAD+ mu butoffaali [2, 7]..
Enkolagana wakati wa NAD+ Biosynthesis n’okukozesa Enzymes n’endwadde:
NAD+ biosynthesis ne consuming enzymes zeenyigira mu makubo amakulu agawerako ag’ebiramu, nga zikosa okuwandiika kw’obuzaale, obubonero bw’obutoffaali, n’okulungamya enzirukanya y’obutoffaali. N’olwekyo, endwadde nnyingi zeekuusa ku mirimu egitali gya bulijjo egy’enziyiza zino. Okugeza, mu ndwadde z’obusimu, enkola ezesigamiziddwa ku NAD+ zirimu obutoffaali nga WLDs, NMNAT2, ne SARM1, ekiraga nti endwadde ezivunda obusimu mu butonde zikwatagana ne NAD+ n’okukyusakyusa amaanyi [4].
Ensibuko:PubMed [7] .
Ennimiro ki ez’okukozesa NAD+?
Okukozesebwa mu ndwadde z’emisuwa n’emisuwa
Enkola y’Obukuumi:
NAD+ ekola kinene mu ndwadde z’emisuwa, era esobola okukuuma omutima okuva ku ndwadde ez’enjawulo. Okugeza, NAD+ esobola okukuuma omutima okuva ku ndwadde nga metabolic syndrome, omutima okulemererwa, ischemia-reperfusion injury, arrhythmia, ne puleesa [1] . Kino kiri bwe kityo kubanga NAD+ ekola nga enziyiza y’okuwulira oba enywa enziyiza nga poly(ADP-ribose) polymerase 1 (PARP1), cyclic ADP-ribose (cADPR) synthases (CD38 ne CD157), ne sirtuin protein deacetylases (Sirtuins, SIRTs), era yeenyigira mu nkola enkulu eziwerako mu ndwadde z’emisuwa.
Okukuuma Bbalansi ya Redox:
Omugerageranyo gwa NAD+/NADH mukulu nnyo mu kukuuma redox homeostasis y’obutoffaali n’okulungamya enkyukakyuka y’amasoboza [1] . N’olwekyo, okukuuma omutindo gwa NAD+ mu mutima oba okukendeeza ku kufiirwa kwayo kikulu nnyo eri obulamu bw’emisuwa.
Enkozesa mu Anti-aging
Okwongera ku bulamu:
Ebivaako okukaddiwa kwa molekyu n’okuyingira mu nsonga z’okuwangaala bibadde byeyongera mu myaka kkumi egiyise. Nicotinamide adenine dinucleotide (NAD) n’ebigisooka, nga nicotinamide riboside, nicotinamide mononucleotide, nicotinamide, ne nicotinic acid, bifunye obwagazi nga molekyu eziyinza okusanyusa mu kukozesa molekyu entonotono ng’ebiyinza okukuuma geroprotectors ne/oba pharmacogenomics. Ebirungo bino biraga nti bisobola okulongoosa embeera ezeekuusa ku kukaddiwa oluvannyuma lw’okubigattako era biyinza okuziyiza okufa kw’ebiramu eby’ekyokulabirako [8]..
Okufuga Enteekateeka y’Obulamu:
Mu biramu eby’ekyokulabirako nga ekizimbulukusa, okunoonyereza kulaga nti ebisookerwako bya NAD bikola kinene mu kukaddiwa n’okuwangaala. Okuyita mu kunoonyereza ku bulamu bw’ebiseera (CLS) n’obulamu obukoppa (RLS) obw’ekizimbulukusa, tusobola okutegeera obulungi enkola y’okukyusakyusa NAD n’omulimu gwayo ogw’okulungamya mu kukaddiwa n’okuwangaala [8]..
Ebiyinza Okukozesebwa mu Kujjanjaba Akafuba
Ekigendererwa ky’Eddagala:
Okuziyiza enziyiza ey’enkomerero ey’okusengejja NAD, NAD synthetase (NadE), mu Mycobacterium tuberculosis (Mtb) kiviirako okukendeera okufaanana mu bidiba bya NAD ne NADP n’okukendeera mu bulamu bwa Mtb, ate okulemererwa kw’enziyiza ey’enkomerero ey’okusengejja obulamu bwa NADP, NAD kinase (PpnK), mu ngeri ey’okulonda okukendeeza ku kidiba kya NADP kyokka ne kiyimiriza (Sharma R, 2023) Enkola y’okusomesa abantu. Kino kiraga nti eddagala eriziyiza okukola NAD lye lirina enkizo mu kukola eddagala eriweweeza ku kafuba, kubanga obutaba na NAD butta obuwuka, ate obutaba na NADP butta obuwuka.
Enkyukakyuka mu nkyukakyuka mu mubiri n’enkula y’obuwuka obutonotono:
Okutakola kwa buli enziyiza kuwerekerwako enkyukakyuka mu nkyukakyuka mu mubiri ezikwata ku enziyiza ekoseddwa n’enkula y’obuwuka obutonotono obukwatagana nayo. Emiwendo gya bacteriostatic egy’okukendeera kwa NAD gireeta okuddamu okuliyirira kw’amakubo g’enkyukakyuka mu mubiri agasinziira ku NAD awatali kukosa mugerageranyo gwa NADH/NAD, ate emitendera egy’okutta obuwuka egy’okukendeera kwa NAD giviirako okutaataaganyizibwa kw’omugerageranyo gwa NADH/NAD n’okuziyiza okussa kwa oxygen [6]..
Omulimu mu Nkyukakyuka y’Obutoffaali
Emirimu Emikulu Emingi:
NAD(H) ne NADP(H) mu buwangwa zibadde zitwalibwa nga cofactors ezikwatibwako mu nsengekera za redox ezitabalika, omuli n’okutambuza obusannyalazo mu mitochondria. Naye, NAD pathway metabolites zirina emirimu emirala mingi emikulu, omuli emirimu mu makubo g’obubonero, enkyukakyuka oluvannyuma lw’okuvvuunula, enkyukakyuka mu epigenetic, n’okulungamya okutebenkera n’enkola ya RNA okuyita mu NAD capping of RNA [9]..
Enkola ya Dynamic Metabolic Enkola:
Enkola ezitali za oxidative ku nkomerero ziviirako net catabolism ya nucleotides zino, ekiraga nti NAD metabolism nkola ya maanyi nnyo. Mu butuufu, okunoonyereza okwakakolebwa kulaga bulungi nti mu bitundu ebimu, ekitundu ky’obulamu bwa NAD kiba nga eddakiika ntono [9]..
Omulimu mu Biology y’Obutoffaali
Enkyukakyuka ya NAD ey’ebweru w’obutoffaali:
NAD ey’ebweru w’obutoffaali ye molekyu enkulu ekola obubonero wansi w’embeera ez’enjawulo ez’omubiri n’endwadde. Kikola butereevu nga kikola ebikwata ku purinergic ebitongole oba mu ngeri etali butereevu nga substrate ya exonucleases (nga CD73, nucleotide pyrophosphatase/phosphodiesterase 1, CD38 ne paralog yaayo CD157, ne ecto-ADP-ribosyltransferases). Enziyiza zino zisalawo okubeerawo kwa NAD ey’ebweru w’obutoffaali nga zisengejja NAD mu mazzi, bwe zityo ne zitereeza ekikolwa kyayo eky’obubonero obutereevu (Gasparrini M, 2021). Okugatta ku ekyo, zisobola okukola molekyu entonotono eziraga obubonero okuva mu NAD, gamba nga adenosine ekyusa obusimu obuziyiza endwadde, oba okukozesa NAD okukola ADP-ribosylate puloteyina ez’enjawulo ez’ebweru w’obutoffaali n’ebikwata olususu, nga zikola kinene ku kufuga abaserikale b’omubiri, okuddamu okuzimba, okuzimba ebizimba, n’endwadde endala. Embeera y’ebweru w’obutoffaali era erimu nicotinamide phosphoribosyltransferase ne nicotinic acid phosphoribosyltransferase, ezitabula enkola enkulu mu kkubo ly’okutaasa NAD mu butoffaali. Ebika by’enziyiza zino eby’ebweru w’obutoffaali bikola nga cytokines ezirina emirimu egy’okuyamba okuzimba [10]..
Mu kumaliriza, NAD+ efuuse molekyu enkulu egatta obulamu n’endwadde nga etereeza enkyukakyuka y’amasoboza, okulwawo okukaddiwa, okulungamya abaserikale b’omubiri, n’okuwa obukuumi eri enkola eziwera. Okwongera ku bigisooka kiyinza okulongoosa enkola ya mitochondria n’okukendeeza ku kukula kw’endwadde z’enkyukakyuka y’emmere n’ez’obusimu. Kiraga obusobozi mu by’okukuuma emisuwa gy’omutima, okulwanyisa yinfekisoni, n’okulwanyisa okukaddiwa, nga kiwa ebigendererwa by’obujjanjabi ebiyiiya ku ndwadde ezeekuusa ku kukaddiwa.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Jiang YF munoonyereza alina akakwate n’amatendekero ag’ettutumu agawerako, omuli Yunivasite ya Peking, Yunivasite ya Lanzhou Jiaotong, ekitongole kya National and Local Joint Engineering Research Center for Technology and Applications, ekitongole ekikola ku kunoonyereza ku yinginiya ne tekinologiya mu Beijing ku by’okwongera ku mmere, Chinese Academy of Sciences, University of Science and Technology of (CAS), Beijing Technology and Business University, ne Medical University. Okunoonyereza kwe kukwata ku bintu bingi omuli kemiko, endwadde, yinginiya, kkansa, n’amaloboozi. Omulimu gwe gulaga enkola ey’enjawulo, ng’agatta enkulaakulana mu bya ssaayansi ne tekinologiya mu bintu bino byonna. Jiang YF awandiikiddwa mu kiwandiiko ekijuliziddwa mu kiwandiiko ekijuliziddwa [5].
