▎ 5-Amino-1MQ Okunoonyereza ku
Kiki ekiva mu kunoonyereza ku 5-Amino-1MQ?
Mu kitundu ekigenda kikulaakulana eky’okunoonyereza ku bulamu bw’enkyukakyuka y’emmere n’obuwangaazi, okuzuula enkola ennungamu okukola ku buzibu bw’enkyukakyuka y’emmere n’okulwawo okukaddiwa kikyali kikulu nnyo mu bya ssaayansi. Nicotinamide N-methyltransferase (NNMT) eraga emirimu mingi mu bitundu by’amasavu n’ekibumba. Nga ekola methylation ya nicotinamide, ekendeeza ku kukyuka kwayo okufuuka nicotinamide adenine dinucleotide (NAD+). NAD+ kikulu nnyo mu nkyukakyuka y’obutoffaali (cellular basal metabolism), okukola amaanyi, okuddaabiriza DNA, n’amakubo g’obubonero. Okukuuma omutindo gwayo ogusinga obulungi kikulu nnyo eri obulamu bw’obutoffaali n’okulwanyisa okukaddiwa n’obutakola bulungi mu nkyukakyuka y’emmere. Mu 2017, abanoonyereza mu yunivasite y’e Texas baasooka kunoonyereza ku 5-Amino-1MQ nga banoonya enkola eziziyiza NNMT. Okusinziira ku kakwate akanywevu NNMT kw’erina n’omugejjo ne sukaali ow’ekika eky’okubiri, abanoonyereza bateebereza nti okuziyiza NNMT kiyinza okuggulawo amakubo amapya ag’okujjanjaba omugejjo n’ebizibu ebivaamu mu nkyukakyuka y’emmere. Kino kye kyakola ekifo ekikulu eky’okunoonyereza ku 5-Amino-1MQ.
Enkola y’okukola ku 5-Amino-1MQ eri etya?
Okuziyiza okukula kw’obutoffaali bwa kookolo w’omumwa gwa nnabaana: 5MQ kiziyiza kya molekyu entono ekya nicotinamide N-methyltransferase (NNMT) eraga ebikolwa eby’amaanyi eby’okulwanyisa okukula ku layini y’obutoffaali bwa kookolo w’omumwa gwa nnabaana mu HeLa epithelial, ng’ekikolwa kino kyesigamye ku bungi n’obudde. NNMT ye nsengekera y’enkyukakyuka mu mubiri ekwatagana n’okukula kw’ekizimba n’okusaasaana. Nga eziyiza NNMT, 5MQ eyinza okutaataaganya omuddirirwa gw’amakubo g’enkyukakyuka mu butoffaali agakwatagana n’okukula kw’ekizimba. Okugeza, 5MQ eyinza okutaataaganya amakubo g’obubonero agakwatagana n’enkyukakyuka ya nicotinamide. Obutakwatagana mu nkyukakyuka ya nicotinamide buyinza okwongera okukosa enkyukakyuka y’amaanyi g’obutoffaali, okuddaabiriza DNA, n’enkola endala, bwe kityo ne kiziyiza okukula kw’obutoffaali bwa kookolo. Mu kugezesa, nga 5MQ concentration yeeyongera n’obudde bw’obujjanjabi bweyongera, HeLa cell proliferation yalaga progressively pronounced inhibition. Mu kiseera kye kimu, enkyukakyuka mu nkula omuli okukendeera kw’obutoffaali, okufiirwa okunywerera wakati w’obutoffaali, n’emibiri egy’okufa zaalabiddwa, ekiraga nti 5MQ ereeta okufa, bwe kityo n’eziyiza okukula kw’obutoffaali [1]..
Regulation of Related Gene and Protein Expression: Oluvannyuma lw’okujjanjaba obutoffaali bwa HeLa mu ngeri ya 5MQ, emiwendo gya mRNA egya ZEB1, SIRT1, ne CD16 gyeyongera, ate emiwendo gya TWIST ne SERPIN1 mRNA gyakendeera. Mu kiseera kye kimu, okwolesebwa kwa puloteyina za oncogenic phospho-Akt ne SIRT1 kwakendeera. Ensengekera z’obuzaale zino ne puloteyina zikola kinene nnyo mu kuzaala ebizimba n’okukula. Okugeza, TWIST ne SERPIN1 zitera okukwatagana n’okuyingira kw’ebizimba n’okusaasaana. Nga ekendeeza ku kwolesebwa kwazo, 5MQ eyinza okunyigiriza obusobozi bw’okuyingira n’okusaasaana kw’obutoffaali bwa HeLa. Newankubadde nga mRNA levels za ZEB1 ne SIRT1 zeeyongera, okwolesebwa kwa oncogenic protein SIRT1 kwakendeera. Kino kiyinza okubaawo kubanga 5MQ ekosa okulungamya oluvannyuma lw’okuwandiika, okuziyiza enkola ya puloteyina ya SIRT1 era bwe kityo n’ekosa okukula kw’obutoffaali n’okuwangaala. Phosphorylated Akt ekola kinene nnyo mu bulamu bw’obutoffaali, okukula, n’okulungamya enkyukakyuka mu mubiri. Okukendeera kwa 5MQ mu kwolesebwa kwayo kuyinza okuziyiza okukula kw’obutoffaali bwa kookolo n’okuwangaala nga kuziyiza amakubo g’obubonero agakwatagana [1]..
Biki ebikozesebwa mu 5-Amino-1MQ?
Mu kunoonyereza ku bulamu bw’enkyukakyuka y’emmere, omulimu gwayo omukulu kwe kuzzaawo bbalansi y’enkyukakyuka y’emmere mu butoffaali nga eziyiza NNMT. NNMT enywa nicotinamide (entandikwa ya NAD+) era ekosa enkyukakyuka y’omugabi wa methyl, ate 5-Amino-1MQ eziyiza enkola eno: ku ludda olumu, ekendeeza ku nkozesa ya nicotinamide methylation mu adipocytes, okulinnyisa emiwendo gya NAD+ mu butoffaali okukola obuzaale obuwangaazi obusinziira ku NAD− (nga SIRT1) n’okulongoosa mitochondrial function— enkola etumbula lipolysis, eziyiza lipogenesis, eyamba okulungamya okukyusakyusa amaanyi mu adipose tissue, era ekendeeza ku kukuŋŋaanyizibwa kw’amasavu agasukkiridde. Ku luuyi olulala, era kikendeeza ku buziyiza bwa insulini obutera okulabibwa mu buzibu bw’enkyukakyuka y’emmere nga kirongoosa okutegeera kw’ekkubo ly’obubonero bwa insulini, ate nga kiyinza okulung’amya mu ngeri etali ya butereevu hepatic gluconeogenesis okuyamba mu kukuuma emiwendo gya glucose mu musaayi nga gitebenkedde. Ekirala, enkosa yaayo eyinza okukwata ku microbiota y’omu byenda eri mu kunoonyerezebwako, nga waliwo okuteebereza nti eyinza okuwagira mu ngeri etali butereevu homeostasis y’enkyukakyuka y’emmere okutwalira awamu nga etereeza emirimu gy’enkyukakyuka y’obuwuka obutonotono (okugeza, okukendeeza ku kukola metabolite ey’obulabe).
Mu kunoonyereza ku kookolo, okugikozesa essira erisinga kulissa ku kutunuulira 'obuzibu bw'emmere y'omubiri' obw'obutoffaali bw'ekizimba. Okusobola okuyimirizaawo okukula okw’amangu, obutoffaali bw’ekizimba butera okwesigama ku makubo g’enkyukakyuka mu mubiri agakola mu ngeri etaali ya bulijjo (nga Warburg effect), era NNMT yeeyolekera nnyo mu butoffaali bw’ekizimba obumu, nga buwagira enkyukakyuka yabwo. Nga eziyiza NNMT, 5-Amino-1MQ etaataaganya enkyukakyuka y’obutoffaali bw’ekizimba mu ngeri bbiri: Esooka, ekendeeza ku miwendo gya NAD+ mu butoffaali, okukosa okukola amaanyi, ekivaako amaanyi agatali gamala n’ebintu ebikola ebiramu ebyetaagisa okukula; Ekyokubiri, kikosa enkozesa y’abagaba methyl, ne kitaataaganya enkola z’okulungamya epigenetic nga DNA methylation mu butoffaali bw’ekizimba, bwe kityo ne kinyigiriza okulaga kw’obuzaale okukwatagana n’okusaasaana n’okusaasaana. Okugatta ku ekyo, kiyinza okuziyiza mu ngeri etali butereevu okukula kw’ekizimba n’okusaasaana nga kikyusakyusa ensonga z’enkyukakyuka mu mubiri mu mbeera entonotono y’ekizimba, ne kiwa omusingi gw’okunoonyereza ku bukodyo bw’okuyingira mu nkyukakyuka y’ebizimba.
Nga ekintu ekikulu eky’okunoonyereza, kikola ng’enkola enkulu ey’okuvvuunula emirimu gya NNMT egy’omubiri. Abanoonyereza basobola bulungi okuziyiza emirimu gya NNMT nga bakozesa 5-Amino-1MQ mu bikolwa by’obutoffaali oba ebisolo okulaba enkyukakyuka eziddako mu bipimo by’enkyukakyuka y’emmere. Okugeza, mu kugezesa obutoffaali, okulondoola ebirungo bya NAD+, emiwendo gy’omugabi wa methyl, n’emirimu gy’enziyiza ezenyigira mu kukola asidi w’amasavu kiyinza okunnyonnyola omulimu ogw’enjawulo ogwa NNMT mu nkyukakyuka y’obutoffaali. Mu bikolwa by’ebisolo, nga bigattiddwa wamu n’okwekenneenya sampuli ezikwata ku bitundu by’omubiri, kisobozesa okunoonyereza ku mirimu gya NNMT egy’ebitundu by’omubiri —nga enkosa yaayo ku nkyukakyuka y’ekibumba mu kiseera ky’okukaddiwa oba okulungamya kwayo okugaba amaanyi mu busimu obuyitibwa neurons. Ate era, okukozesa eby’okuddamu eby’enjawulo mu layini z’obutoffaali (okugeza, obutoffaali obwa bulijjo obulaga obuwulize obutono okusinziira ku kuddamu okumanyiddwa mu butoffaali obutali bwa bulijjo mu mubiri oba obw’ekizimba) kiyinza okuyamba mu kuvvuunula enkola ez’enjawulo ez’okukyusakyusa obutoffaali, okulungamya okunoonyereza okuddirira okugendereddwamu.
Mu bitundu by'obulamu bw'ebinywa n'okutegeera, okukozesebwa kwayo kwesigamye ku nkolagana ya 'okukyusakyusa amaanyi - enkola y'obutoffaali'. Mu kunoonyereza ku bulamu bw’ebinywa, okuddaabiriza ebinywa kwesigamye ku kukola n’okusaasaana kw’obutoffaali bwa setilayiti, enkola eyeetaaga okuweebwa amaanyi agamala. —5-Amino-1MQ etumbula okukola kw’obutoffaali bwa satellite nga ekuuma emiwendo gya NAD+ mu butoffaali mu butoffaali bw’ebinywa. Mu kiseera kye kimu, erongoosa enkola ya mitochondrial okutumbula obulungi bw’okukyusakyusa amaanyi g’ebinywa, okukendeeza ku situleesi y’okudda engulu oluvannyuma lw’obuvune bw’ebinywa. Era kiyinza okukendeeza ku situleesi y’okwokya (oxidative stress) mu bitundu by’ebinywa, okukuuma obutoffaali okuva ku kwonooneka okuva ku biva mu nkyukakyuka y’emmere ebisusse. Mu kunoonyereza ku kutegeera, obusimu bw’obwongo bulaga obwetaavu bw’amaanyi amangi ennyo, era okukendeera kw’emiwendo gya NAD+ kukwatagana n’okukendeera kw’emirimu gy’obusimu. 5-Amino-1MQ ekuuma okugabibwa kw’obusimu bwa NAD+ nga eziyiza NNMT, bwe kityo n’ekuuma enkola ya mitochondrial n’okukendeeza ku kuzimba kw’obusimu. Era kiyinza okukwata ku nkyukakyuka y’obusimu obutambuza (nga kiyita mu NAD+-dependent enzymes involved mu neurotransmitter synthesis) okuwagira cognitive-related neuronal activity (okugeza, enkola y’obutoffaali mu kuyiga/okujjukira ebitundu nga hippocampus), okuwa endowooza empya ku cognitive function maintenance research.
Mu bufunzi
Nga ekiziyiza ekitongole ekya nicotinamide N-methyltransferase (NNMT), 5-Amino-1MQ eraga omugaso omukulu mu bitundu ebingi nga etunuulira amakubo g’enkyukakyuka mu mubiri agafugibwa NNMT. Kiyinza okulongoosa omugejjo n’okuziyiza insulini nga kikuuma emiwendo gya NAD+, okulongoosa enkola ya mitochondrial, n’okuzzaawo bbalansi y’enkyukakyuka y’emmere. Era etunuulira obuzibu bw’enkyukakyuka y’emmere mu butoffaali bw’ekizimba, okutaataaganya okukola amaanyi gaabwe n’okulungamya epigenetic okuziyiza okukula kw’ekizimba. Ekirala, kikola ng’ekintu eky’okunoonyereza okunnyonnyola enkola ya NNMT ate nga kiraga emirimu egisobola okukolebwa mu kuddaabiriza ebinywa n’okulabirira okutegeera, nga kiwa endagiriro enkulu ez’okunoonyereza okuyingira mu nsonga mu ndwadde z’enkyukakyuka mu mubiri, kookolo, n’embeera ezikwatagana nabyo.
Ebikwata ku Muwandiisi
Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.
Omuwandiisi wa Scientific Journal
Akar s munoonyereza ng’omulimu gwe gusinga kutunuulira nkola za molekyu n’okuyingira mu nsonga z’obujjanjabi. Abadde ayambako mu kunoonyereza okunoonyereza ku kifo kya enzymes n’ebiziyiza molekyu entono mu kulungamya okukula kw’obutoffaali. Okunoonyereza kwe kuggumiza obukulu bw’okutunuulira amakubo g’enkyukakyuka mu mubiri, nga nicotinamide N-methyltransferase, okunoonyereza ku bukodyo obupya obw’obusawo bw’ebiramu.Akar s ewandiikiddwa mu kiwandiiko ekijuliziddwa [2].
