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1kits (Ebipipa 10) .
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▎ Enzimba ya 5-Amino-1MQ
Ensibuko: PubChem |
Ensengekera ya molekyu: C 10H 11N 2+ Obuzito bwa molekyu: 159.21 g/mol Ennamba ya CAS: 685079-15-6 Ekitongole kya PubChem CID:950107 Ebigambo ebikwatagana: 5-amino-1-methylquinolinium;PMX593N4N3 |
▎ 5-Amino-1MQ Okunoonyereza ku
Kiki ekiva mu kunoonyereza ku 5-Amino-1MQ?
Olw’okulinnya okutambula kw’emiwendo gy’endwadde z’enkyukakyuka mu mubiri mu nsi yonna ng’omugejjo ne ssukaali, okuzuula ebigendererwa n’eddagala eriyinza okulung’amya obulungi enkyukakyuka y’amaanyi n’okulongoosa obuzibu mu nkyukakyuka y’emmere kifuuse ekintu ekikulu eky’okunoonyereza. Nicotinamide N-methyltransferase (NNMT), enziyiza enkulu ey’okukyusakyusa emmere, ekola kinene nnyo mu kuziyiza amaanyi. Okwolesebwa kwayo okusukkiridde kuleeta ensonga ng’okukuŋŋaanyizibwa kw’amasavu n’okuziyiza insulini, ekifuula okulungamya NNMT ekigendererwa ekiyinza okujjanjaba endwadde ezikwatagana.
Mu mbeera eno, 5-Amino-1MQ evuddeyo ng’ekiziyiza kya NNMT ekigere. Nga kinyigiriza emirimu gya NNMT, ekendeeza ku methylation ya nicotinamide etali ya bulijjo, ezzaawo emiwendo gya NAD+ mu butoffaali n’okuzzaawo amakubo g’obubonero agakwatagana, bwe kityo ne kitereeza enkyukakyuka y’amasavu n’okutumbula okuwuliziganya kwa insulin. 5-Amino-1-methylquinolinium evuddeyo ng’ekigendererwa ekikulu eky’okunoonyereza okunoonyereza ku bukodyo obupya obw’obujjanjabi ku buzibu bw’enkyukakyuka y’emmere, ekivuddeko okunoonyereza okukulu ku nkola zaayo.
Biki 5-Amino-1-methylquinolinium by’akola ku nkyukakyuka y’obutoffaali bw’amasavu?
Ebikosa ku Adipogenesis
Okuziyiza Adipogenesis: Adipogenesis kitegeeza enkola nga preadipocytes zaawukana ne zifuuka adipocytes ezikuze ne zikung’aanya lipids mu kiseera ky’okukula kw’obutoffaali bw’amasavu. Okunoonyereza kulaga nti methylquinolinium scaffolds ezirina primary amine substituents ziraga okuyingira okw’amaanyi ku byombi passive ne active transmembrane transport, ate nga analogues zazo ziraga highly selective inhibitory activity against nicotinamide N-methyltransferase (NNMT) [1] . Ebiziyiza NNMT binyigiriza adipogenesis mu adipocytes, ekivaako endowooza nti 5-Amino-1-methylquinolinium, singa eba n’omulimu ogufaanagana ogw’okuziyiza NNMT, eyinza nnyo okukendeeza ku adipogenesis nga eziyiza NNMT. Okugeza, mu kugezesa obutoffaali bw’amasavu obukuziddwa, ebiziyiza NNMT bikendeeza ku miwendo gya 1-methylnicotinamide (1-MNA) mu butoffaali, byongera mu butoffaali nicotinamide adenine dinucleotide (NAD0) ne S-(5’-adenosyl) -L-methionine (SAM), era biziyiza amasavu mu butoffaali bw’amasavu [1] ..
Okukwata ku kwolesebwa kw’obuzaale obukwatagana n’okutondebwa kw’amasavu: Okutondebwa kw’amasavu kufugibwa omuddirirwa gw’ensonga eziwandiika n’obuzaale, nga peroxisome proliferator-activated receptor-gamma (PPAR-γ) ne CCAAT/enhancer-binding protein (C/EBP). Ebiva mu Methylquinoline tekyewalika bikwata ku lipogenesis nga bikosa okwolesebwa kw’obuzaale buno obukulu.
Ekifaananyi 1 Ebiziyiza molekyu entono ebirondeddwa era ebiyita mu lususu ebya nicotinamide N-methyltransferase bizzaawo omugejjo oguva mu mmere erimu amasavu amangi mu mbeba.
Ensibuko: SayansiDirect [1]
Ebikosa Enkyukakyuka y’Amasavu (Lipid Metabolism).
Okulungamya obutoffaali obukwatibwako mu kukola n’okuvunda kw’amasavu: Enkyukakyuka y’amasavu ezingiramu enkola nga okukola amasavu, okutereka, n’okuvunda. Mu kunoonyereza ku bulwadde bw’ekibumba obukwatagana n’enkyukakyuka y’emmere (MAFLD), Donglingcao ekyusa emirimu gya peroxisome proliferator-activated receptor -α (PPAR-α), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), ne acetyl-CoA carboxylase (ACC). 5-Amino-1-methylquinolinium eyinza okukwata ku nkyukakyuka y’amasavu mu adipocytes ng’eyita mu nkola efaananako bwetyo, kwe kugamba ng’elungamya okwolesebwa kwa puloteyina zino enkulu ezikwatibwako mu kukola n’okuvunda kw’amasavu. Okugeza, singa 5-Amino-1-methylquinolinium esobola upregulate PPAR-α expression, eyinza okutumbula fatty acid oxidation n’okukendeeza ku kukuŋŋaanyizibwa kw’amasavu mu adipocytes. Okwawukana ku ekyo, singa kikosa okwolesebwa kwa SREBP-1c, FAS, n’ebirala, kiyinza okukosa enkola z’okukola asidi w’amasavu.
Okukyusa emiwendo gy’ebirungo ebikyukakyuka mu butoffaali okufuga enkyukakyuka y’amasavu: Emiwendo gy’ebirungo ebikyukakyuka mu butoffaali gikola kinene nnyo mu kulungamya mu nkyukakyuka y’amasavu. Nga bwe kyayogeddwako emabegako, ebiziyiza NNMT bisobola okukyusa emitendera egy’omu butoffaali egy’ebirungo ebikyusa ebiriisa nga 1-MNA, NAD+, ne SAM, bwe kityo ne kikosa enkyukakyuka y’obutoffaali bw’amasavu [1] . Singa 5-Amino-1-methylquinolinium ekola ebikolwa ebifaanagana ku miwendo gino egy’ebirungo ebikyusa ebiriisa, yandibadde etereeza enkyukakyuka y’amasavu mu ngeri etali butereevu. Nga coenzyme enkulu ey’omu butoffaali eyenyigira mu makubo amangi ag’enkyukakyuka mu mubiri, enkyukakyuka mu miwendo gya NAD+ ziyinza okukosa enkola ezeekuusa ku nkyukakyuka y’amasavu nga fatty acid oxidation ne tricarboxylic acid cycle.
Ebikosa Enkyukakyuka y’Amaaso
Ebikosa emirimu gya Mitochondrial: Enkyukakyuka y’amasoboza mu adipocytes ekwatagana nnyo n’enkola ya mitochondria. Okunoonyereza kulaga nti wansi w’embeera z’okugolola ezikoppa mu kisenge (in vitro simulated static stretching conditions), emirimu gya mitochondrial mu adipocytes gyeyongera, okutumbula lipogenesis n’okwanguyiza okukyusakyusa obutoffaali [2] . Ebirungo bya methylquinolinium biyinza okukyusa emirimu gya mitochondria nga bikwata ku makubo g’enkyukakyuka mu mubiri agakwatagana ne mitochondrial oba okulaga kwa puloteyina. Singa 5-Amino-1-methylquinolinium eziyiza obutoffaali obumu obukulu obwa mitochondria oba enkola z’okukyusakyusa ebiriisa, eyinza okukendeeza ku mirimu gya mitochondria n’okukendeeza ku nsaasaanya y’amasoboza mu adipocytes. Okwawukana ku ekyo, kiyinza okutumbula okukyusakyusa amaanyi. Okugeza, nga ekosa emirimu gya mitochondrial respiratory chain complexes, eyinza okulungamya okukola ATP, bwe kityo ne kikwata ku mbeera y’amasoboza n’obulagirizi bw’enkyukakyuka y’emmere y’obutoffaali bw’amasavu.
Okulungamya bbalansi y’amasoboza g’obutoffaali bw’amasavu: Amasavu tegakoma ku kutereka maanyi wabula era geetaba mu kulungamya bbalansi y’amasoboza. Ebikolwa bya 5-Amino-1-methylquinolinium ku nkyukakyuka y’obutoffaali bw’amasavu ku nkomerero biyinza okweyoleka mu kulungamya bbalansi y’amasoboza. Singa kiziyiza okukola amasavu n’okutumbula okuzimba amasavu, kiyinza okukendeeza ku kutereka amaanyi n’okwongera okufulumya amaanyi mu adipocytes. Okwawukana ku ekyo, singa kitumbula okukola amasavu n’okuziyiza okusasika kw’amasavu, kiyinza okuvaako okukuŋŋaanyizibwa kw’amaanyi okuyitiridde mu bitundu by’amasavu, ne kitaataaganya bbalansi y’amasoboza —ensonga enkulu mu kukula kw’omugejjo n’obuzibu obukwatagana n’enkyukakyuka y’emmere.
Ebikosa Enkola ya Adipocyte Endocrine
Ekwata ku kufulumya adipokine: Nga ebitundu by’omubiri, adipocytes zifulumya adipokines eziwera nga leptin ne adiponectin, ezikola emirimu emikulu egy’okulungamya mu nkyukakyuka y’omubiri mu nkola [3] . Eddagala oba ebintu ebimu bisobola okukosa okufulumya adipocyte mu adipokines zino. Wadde nga tewali bujulizi butereevu buliwo ku bikwata ku 5-Amino-1-methylquinolinium’s effect ku adipokine secretion, okutwalira awamu impact yaayo ku adipocyte metabolism eraga nti eyinza okulungamya indirect okufulumya adipokine. Singa 5-Amino-1-methylquinolinium ekyusa embeera y’amasoboza g’obutoffaali bw’amasavu oba enkyukakyuka y’amasavu, eyinza okuddamu-okutereeza okufulumya leptin. Nga molekyu ekola obubonero eraga amasavu agaterekeddwa, enkyukakyuka mu kufulumya leptin zikwata ku njagala y’okulya n’okukyusakyusa amaanyi.
Influencing Inflammatory Cytokine Secretion: Embeera y’okuzimba ey’ebitundu by’amasavu ekwatagana nnyo n’enkyukakyuka y’obutoffaali bw’amasavu. Obutoffaali bw’amasavu busobola okufulumya obusimu obw’enjawulo obuzimba, gamba nga interleukin-1β (IL-1β), interleukin-6 (IL-6), ne tumor necrosis factor-α (TNF-α) (Michalczyk K). Mu mbeera z’omugejjo, okweyongera kw’okuzimba kw’ebitundu by’amasavu kuleeta okufulumya ennyo ensonga zino ezizimba, oluvannyuma ne kikosa enkyukakyuka y’omubiri n’okuwulira insulini. 5-Amino-1-methylquinolinium, singa esobola okulungamya enkyukakyuka y’obutoffaali bw’amasavu, eyinza okukyusa okufulumya kwa cytokine, bwe kityo n’ekwata ku butonde obutono obuzimba obw’ebitundu by’amasavu n’okukosa ebizibu by’enkyukakyuka y’omubiri ebikwatagana n’omugejjo. Obusobozi bwayo okuziyiza okufulumya cytokine buyinza okuyamba okukendeeza ku buziyiza bwa insulini n’okulongoosa embeera y’enkyukakyuka y’emmere.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Harshini Neelakantan ye munnasayansi mu by’eddagala era omukulembeze w’okunoonyereza ng’alina obumanyirivu bungi mu kukola eddagala erisooka okujjanjaba obulwadde bw’enkyukakyuka y’emmere, obusimu n’ebinywa. Mu kiseera kino akola nga Executive Director of Research & Development mu Ridgeline Therapeutics, ng’essira aliteeka ku kuvvuunula obujjanjabi bwa molekyu entono okuva ku kukakasa okukuba okutuuka ku kukulembera okudda ku kukozesebwa mu bujjanjabi. Obukugu bwe bukwata ku ddagala mu mubiri, okukoppa endwadde, n’okukyusakyusa eddagala, era emabegako yakolera mu Yunivasite y’e Texas Medical Branch.Harshini Neelakantan awandiikiddwa mu kiwandiiko ekijuliziddwa mu kiwandiiko ekijuliziddwa [1].
