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1kits (10Vials) .
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▎ 5-Amino-1MQ ƒe Dɔwɔɖoɖo
Dzɔtsoƒe: PubChem |
Molekyulãwo ƒe Mɔfiame: C 10H 11N 2+ Molekyulã ƒe Kpekpeme: 159.21 g/mol CAS ƒe xexlẽdzesi: 685079-15-6 PubChem ƒe CID:950107 Nya siwo sɔ kple wo nɔewo: 5-amino-1-methylquinolinium;PMX593N4N3 |
▎ 5-Amino-1MQ Numekuku
Nukae nye numekuku si wowɔ le 5-Amino-1MQ ŋu?
Esi lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe dɔlélewo abe lolo akpa kple suklidɔ ene ƒe dzidziɖedzi le xexeame katã ta la, dzesidede taɖodzinuwo kple atike siwo ate ŋu aɖɔ ŋusẽ ƒe asitɔtrɔ nyuie ɖo eye woana lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe kuxiwo nanyo ɖe edzi va zu numekuku vevi aɖe. Nicotinamide N-methyltransferase (NNMT), si nye lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe enzyme vevi aɖe, wɔa akpa vevi aɖe le ŋusẽ ƒe homeostasis me. Eƒe ɖeɖefia fũ hea nyawo abe ami ƒe ƒuƒoƒo kple insulin ƒe dɔlélenutsiŋutete ene vɛ, si wɔnɛ be NNMT ƒe ɖoɖowɔwɔ nye atike si woate ŋu azã na dɔléle siwo do ƒome kplii.
Le nɔnɔme sia me la, 5-Amino-1MQ do abe NNMT mɔxenu tɔxɛ aɖe ene. To NNMT ƒe dɔwɔwɔ tete ɖe anyi me la, eɖea nicotinamide methylation si mesɔ o dzi kpɔtɔna, egbugbɔa NAD+ ƒe agbɔsɔsɔ si le lãmenugbagbeviwo me ɖoa anyi eye wònaa dzesimɔ siwo do ƒome kplii la nɔa ɖoɖo nu, si wɔnɛ be ami ƒe asitɔtrɔ le lãmenugbagbeviwo ŋu nyona ɖe edzi eye wònaa insulin ƒe seselelãme dzina ɖe edzi. 5-Amino-1-methylquinolinium do abe numekuku ƒe taɖodzinu vevi aɖe ene hena atikewɔwɔmɔnu yeyewo me dzodzro ɖe lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe dɔlélewo ŋu, si ʋã numekuku veviwo tso eƒe mɔnuwo ŋu.
Ŋusẽ kae 5-Amino-1-methylquinolinium kpɔna ɖe ami ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ dzi?
Ŋusẽkpɔɖeamedzi ɖe Adipogenesis dzi
Adipogenesis ƒe mɔxexe: Adipogenesis fia alesi preadipocytes toa vovo zua adipocyte tsitsiwo eye woƒoa lipids nu ƒu le adipocyte ƒe tsitsi me. Numekukuwo ɖee fia be methylquinolinium scaffolds siwo me amine substituents gbãtɔwo le la ɖea permeability gã aɖe fiana na passive kple active transmembrane transport siaa, esime woƒe analogues ɖea mɔxexeɖedɔléle si tiaa nu ŋutɔ fiana ɖe nicotinamide N-methyltransferase (NNMT) ŋu [1] . NNMT mɔxenuwo tea ami ƒe dzɔdzɔ ɖe to le ami lãmenugbagbeviwo me, si wɔnɛ be wosusunɛ be 5-Amino-1-methylquinolinium, ne NNMT mɔxenu ƒe dɔwɔwɔ ma tɔgbe le esi la, ate ŋu aɖe ami ƒe dzɔdzɔ dzi akpɔtɔ ŋutɔ to mɔxexe ɖe NNMT nu me. Le kpɔɖeŋu me, le ami ƒe dodokpɔ siwo wode agble me la, NNMT mɔxenuwo ɖea lãmenugbagbeviwo me 1-methylnicotinamide (1-MNA) ƒe agbɔsɔsɔ dzi kpɔtɔna, dzia lãmenugbagbeviwo me nicotinamide adenine dinucleotide (NAD0) kple S-(5’-adenosyl) -L-methionine (SAM) ɖe edzi, eye woxea mɔ na ami ƒe dzɔdzɔ le ami lãmenugbagbeviwo me [1] ..
Ŋusẽkpɔkpɔ ɖe domenyiŋusẽfianu ƒe ɖeɖefia si do ƒome kple ami ƒe dzɔdzɔ dzi: Nuŋɔŋlɔ ƒe nusiwo kple domenyiŋusẽfianu vovovowoe kpɔa ŋusẽ ɖe ami ƒe dzɔdzɔ dzi, abe peroxisome proliferator-activated receptor-gamma (PPAR-γ) kple CCAAT/enhancer-binding protein (C/EBP) ene. Methylquinoline ƒe nusiwo woɖe tso eme kpɔa ŋusẽ ɖe lipogenesis dzi godoo to ŋusẽkpɔkpɔ ɖe domenyiŋusẽfianu vevi siawo ƒe ɖeɖefia dzi.
Nɔnɔmetata 1 Nicotinamide N-methyltransferase ƒe molecule sue siwo tiaa eye woate ŋu age ɖe lãkusi me la trɔa lolo akpa si ami sɔ gbɔ ɖo ƒe nuɖuɖu hena vɛ le sisiblisiwo me.
Dzɔtsoƒe: ScienceDirect [1] .
Ŋusẽkpɔɖeamedzi ɖe Lipid Metabolism Dzi
Protein siwo kpɔa gome le ami ƒe wɔwɔme kple woƒe gbegblẽ me ƒe ɖoɖowɔwɔ: Lãmetsi ƒe asitɔtrɔ lɔ dɔwɔwɔwo abe ami ƒe wɔwɔme, edzadzraɖo, kple eƒe gbegblẽ ɖe eme. Le numekuku siwo wowɔ tso ami ƒe aklãdɔ si do ƒome kple lãmenugbagbeviwo ƒe dɔwɔwɔ (MAFLD) ŋu me la, Donglingcao trɔa asi le peroxisome proliferator-activated receptor -α (PPAR-α), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), kple acetyl-CoA carboxylase (ACC) ƒe dɔwɔwɔ ŋu. 5-Amino-1-methylquinolinium ate ŋu akpɔ ŋusẽ ɖe ami ƒe asitɔtrɔ le ami me dzi to mɔnu ma tɔgbe dzi, si nye to protein vevi siawo siwo kpɔa gome le ami ƒe wɔwɔme kple woƒe gbegblẽ me ƒe ɖeɖefia dzi kpɔkpɔ me. Le kpɔɖeŋu me, ne 5-Amino-1-methylquinolinium ate ŋu ana PPAR-α ƒe ɖeɖefia nadzi ɖe edzi la, ate ŋu ado ami ƒe oxidation ɖe ŋgɔ eye wòaɖe ami ƒe ƒoƒo ɖe ami lãmenugbagbeviwo me dzi akpɔtɔ. Le go bubu me la, ne ekpɔ ŋusẽ ɖe SREBP-1c, FAS, kple bubuawo ƒe ɖeɖefia dzi la, ate ŋu akpɔ ŋusẽ ɖe ami ƒe wɔwɔme ƒe ɖoɖowo dzi.
Lãmenugbagbeviwo me lãmenugbagbeviwo ƒe agbɔsɔsɔ tɔtrɔ be woakpɔ ŋusẽ ɖe ami ƒe asitɔtrɔ dzi: Lãmenugbagbeviwo me lãmenugbagbeviwo ƒe agbɔsɔsɔ wɔa akpa vevi aɖe le ɖoɖowɔwɔ me le ami ƒe asitɔtrɔ me. Abe alesi míegblɔe va yi ene la, NNMT mɔxenuwo ate ŋu atrɔ asi le lãmenugbagbeviwo me ƒe agbɔsɔsɔme si le lãmenugbagbeviwo me abe 1-MNA, NAD+, kple SAM ene ŋu, si ana woakpɔ ŋusẽ ɖe ami ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ dzi [1] . Ne 5-Amino-1-methylquinolinium hã wɔa ŋusẽ ma tɔgbe ɖe metabolite siawo ƒe agbɔsɔsɔ dzi la, aɖɔ lipid metabolism ɖo le mɔ si mele tẽ o nu. Abe lãmenugbagbeviwo me coenzyme vevi aɖe si kpɔa gome le lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe mɔnu geɖewo me ene la, tɔtrɔ siwo vaa NAD+ ƒe agbɔsɔsɔ me ate ŋu akpɔ ŋusẽ ɖe lipid ƒe asitɔtrɔ le dɔwɔwɔ ŋu abe ami ƒe oxidation kple tricarboxylic acid ƒe tsatsam ene dzi.
Ŋusẽkpɔɖeamedzi ɖe Ŋusẽ ƒe Tɔtrɔ Kpata Dzi
Ŋusẽkpɔɖeamedzi ɖe Mitochondria ƒe Dɔwɔwɔ Dzi: Ŋusẽ ƒe asitɔtrɔ le ami lãmenugbagbeviwo me do ƒome kplikplikpli kple mitochondria ƒe dɔwɔwɔ. Numekukuwo ɖee fia be le in vitro simulated static stretching nɔnɔmewo me la, mitochondrial ƒe dɔwɔwɔ le adipocytes me dzina ɖe edzi, si doa lipogenesis ɖe ŋgɔ eye wònaa lãmenugbagbeviwo ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ kabakaba [2] . Methylquinolinium ƒe atikewo ate ŋu atrɔ mitochondrial ƒe dɔwɔwɔ to ŋusẽkpɔkpɔ ɖe mitochondrial-siwo do ƒome kple lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe mɔnuwo alo protein ƒe ɖeɖefia dzi. Ne 5-Amino-1-methylquinolinium xe mɔ ɖe mitochondrial protein vevi aɖewo alo lãmenugbagbeviwo ƒe dɔwɔwɔ nu la, ate ŋu aɖe mitochondrial ƒe dɔwɔwɔ dzi akpɔtɔ eye wòaɖe ŋusẽzazã le adipocytes me dzi akpɔtɔ. Le go bubu me la, ate ŋu ado ŋusẽ ƒe asitɔtrɔ le lãmenugbagbeviwo ŋu ɖe ŋgɔ. Le kpɔɖeŋu me, ne ekpɔ ŋusẽ ɖe mitochondrial gbɔgbɔtsixe ƒe kɔsɔkɔsɔ ƒe dɔwɔwɔ dzi la, ate ŋu aɖɔ ATP wɔwɔ ɖo, si ana akpɔ ŋusẽ ɖe ŋusẽ ƒe nɔnɔme kple ami ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe mɔfiame dzi.
Ami ƒe ŋusẽ ƒe dadasɔ dzi kpɔkpɔ: Menye ɖeko ami lãmenugbagbeviwo dzraa ŋusẽ ɖo ko o, ke wokpɔa gome le ŋusẽ ƒe dadasɔ ƒe ɖoɖowɔwɔ hã me. 5-Amino-1-methylquinolinium ƒe ŋusẽkpɔɖeamedzi ɖe adipocyte ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ dzi ate ŋu adze le ŋusẽ ƒe dadasɔ ƒe ɖoɖowɔwɔ me mlɔeba. Ne exea mɔ na ami ƒe dzɔdzɔ eye wòdoa ami ƒe ʋuʋu ɖe ŋgɔ la, ate ŋu aɖe ŋusẽ ƒe dzadzraɖo dzi akpɔtɔ eye wòana ŋusẽ si dona le ami me nadzi ɖe edzi. Le go bubu me la, ne edoa ami ƒe dzɔdzɔ ɖe ŋgɔ eye wòxea mɔ na ami ƒe ʋuʋu la, ate ŋu ana ŋusẽ naƒo ƒu fũ akpa ɖe ami lãmenugbagbeviwo me, si agblẽ ŋusẽ ƒe dadasɔ me—si nye nu vevi aɖe si na lolo akpa kple lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe kuxi siwo do ƒome kplii ƒe dzɔdzɔ.
Ŋusẽkpɔɖeamedzi ɖe Adipocyte Endocrine Dɔwɔwɔ Dzi
Ekpɔa ŋusẽ ɖe adipokine ƒe dodo dzi: Abe lãmenugbagbeviwo ƒe ŋutinuwo ene la, adipocytes ɖea adipokines geɖe abe leptin kple adiponectin ene, siwo wɔa akpa vevi aɖe le ɖoɖowɔwɔ me le ɖoɖowɔɖi ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ me [3] . Atike alo nu aɖewo ate ŋu akpɔ ŋusẽ ɖe adipokine siawo ƒe dodo le adipocyte me dzi. Togbɔ be kpeɖodzi aɖeke meli tẽ ku ɖe ŋusẽ si 5-Amino-1-methylquinolinium kpɔna ɖe adipokine ƒe dodo dzi ŋu o hã la, ŋusẽ si wòkpɔna ɖe adipocyte ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ dzi bliboa ɖee fia be ate ŋu awɔ ɖoɖo ɖe adipokine ƒe dodo ŋu le mɔ si mele tẽ o nu. Ne 5-Amino-1-methylquinolinium trɔ ami ƒe ŋusẽ ƒe nɔnɔme alo ami ƒe asitɔtrɔ la, ate ŋu aɖɔ leptin ƒe dodo ɖo le nyaŋuɖoɖo me. Abe dzesi molecule si ɖea amidzraɖoƒewo fiana ene la, tɔtrɔ siwo vaa leptin ƒe dodo me kpɔa ŋusẽ ɖe nuɖuɖudzroame kple ŋusẽ ƒe asitɔtrɔ dzi.
Ŋusẽkpɔɖeamedzi le Dzoxɔxɔ ƒe Cytokine ƒe Ʋuʋu Ŋu: Ami ƒe lãkusi ƒe dɔdzẽ ƒe nɔnɔme do ƒome kplikplikpli kple ami ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ. Adipocytes ate ŋu aɖe dɔdzẽ ƒe cytokines vovovowo, abe interleukin-1β (IL-1β), interleukin-6 (IL-6), kple tumor necrosis factor-α (TNF-α) (Michalczyk K) ene. Le lolo akpa ƒe nɔnɔmewo me la, ami ƒe lãmenugbagbeviwo ƒe dɔdzẽ si dzina ɖe edzi nana dɔdzẽ siawo ƒe dodo dzina ɖe edzi, eye emegbe wògblẽa nu le ɖoɖowɔɖi ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ kple insulin ƒe dɔwɔwɔ ŋu. 5-Amino-1-methylquinolinium, ne ate ŋu aɖɔ ami ƒe lãmenugbagbeviwo ƒe dɔwɔwɔ ɖo la, ate ŋu atrɔ cytokine ƒe dodo, si ana wòakpɔ ŋusẽ ɖe ami ƒe lãkusi ƒe dɔdzẽ ƒe nuto suewo dzi eye wòakpɔ ŋusẽ ɖe lãmenugbagbeviwo ƒe dɔwɔwɔ ƒe kuxi siwo do ƒome kple lolo akpa dzi. Ŋutete si le esi be wòaxe mɔ ɖe cytokine ƒe dodo nu ate ŋu akpe ɖe insulin ƒe dɔlélenutsiŋutete dzi akpɔtɔ eye wòana lãmenugbagbeviwo ƒe dɔwɔwɔ nanyo ɖe edzi.
Le Agbalẽŋlɔla La Ŋu
Nusiwo míeyɔ ɖe etame la katã nye esiwo ŋu Cocer Peptides wɔ numekuku le, trɔ asi le wo ŋu eye woƒo wo nu ƒu.
Dzɔdzɔmeŋutinunya ƒe Agbalẽŋlɔla
Harshini Neelakantan nye atikeŋutinunyala kple numekuku kplɔla si si nuteƒekpɔkpɔ geɖe le le atikewo wɔwɔ do ŋgɔ na dɔdamɔnu si wozãna na lãmenugbagbeviwo ƒe dɔwɔwɔ, ahɔhɔ̃mekawo, kple lãmekawo ƒe dɔlélewo me. Fifia ele dɔ wɔm abe Numekuku & Ŋgɔyiyi ƒe Dɔdzikpɔlagã le Ridgeline Therapeutics, eye wòléa fɔ ɖe atikewɔwɔ siwo me molecule suewo le gɔmeɖeɖe tso hit-to-lead validation dzi yi dɔdamɔnu zazã me ŋu. Eƒe nunya ku ɖe atikeŋutinunya le agbe me, dɔléle ƒe kpɔɖeŋuwɔwɔ, kple atikewo ƒe asitɔtrɔ le lãmenugbagbeviwo me ŋu, eye wòwɔ dɔ le Texas Yunivɛsiti ƒe Atikewɔwɔ ƒe Alɔdzedɔwɔƒe va yi.Woŋlɔ Harshini Neelakantan ŋkɔ ɖe nyayɔyɔ ƒe numekugbalẽ me [1].
