▎ 5-Amino-1MQ Nchọpụta
Kedu ihe ndabere nyocha nke 5-Amino-1MQ?
N'ime mpaghara na-agbanwe agbanwe nke ahụike metabolic na nyocha ogologo ndụ, ịchọpụta ihe ndị dị mma iji dozie nsogbu metabolic na igbu oge ịka nká ka bụ isi ihe sayensị lekwasịrị anya. Nicotinamide N-methyltransferase (NNMT) na-egosipụta ọrụ dị elu na anụ ahụ adipose na imeju. Site na methylating nicotinamide, ọ na-ebelata ntụgharị ya na nicotinamide adenine dinucleotide (NAD⁺). NAD⁺ dị mkpa maka metabolism basal cell, mmepụta ume, nrụzi DNA, na ụzọ akara. Idokwa ọkwa ya kachasị mma dị mkpa maka ahụike cellular yana ịlụso ịka nká na arụ ọrụ metabolic ọgụ. Na 2017, ndị nchọpụta na Mahadum Texas buru ụzọ nyochaa 5-Amino-1MQ mgbe ha na-achọ ụzọ iji gbochie NNMT. Nyere njikọ siri ike nke NNMT na oke ibu na ụdị ọrịa shuga 2, ndị nyocha ahụ chere na igbochi NNMT nwere ike imepe ụzọ ọhụrụ maka ịgwọ oke ibu na nsogbu metabolic ya. Nke a mebere ndabere dị oke egwu maka nyocha 5-Amino-1MQ.
Gịnị bụ usoro nke omume maka 5-Amino-1MQ?
Na-egbochi mgbasa mkpụrụ ndụ cancer cervical: 5MQ bụ obere ihe mgbochi nke nicotinamide N-methyltransferase (NNMT) nke na-egosipụta mmetụta mgbochi dị ịrịba ama na HeLa epithelial cervical carcinoma cell line, na mmetụta a bụ ntinye uche- na oge dabere. NNMT bụ enzyme metabolic jikọtara ya na ọganihu etuto na metastasis. Site na igbochi NNMT, 5MQ nwere ike imebi usoro ụzọ metabolic intracellular jikọtara ya na uto tumor. Dịka ọmụmaatụ, 5MQ nwere ike igbochi nicotinamide metabolism metụtara ụzọ mgbaàmà. Enweghị ahaghị nhata na metabolism nicotinamide nwere ike imetụta metabolism ike cell, nrụzi DNA, na usoro ndị ọzọ, si otú a na-egbochi mmụba mkpụrụ ndụ kansa. N'ime nnwale, ka ntinye uche 5MQ na-abawanye na ogologo oge ọgwụgwọ, mmụba cell HeLa gosipụtara mmachi nke na-aga nke ọma. N'otu oge ahụ, a na-ahụ mgbanwe mgbanwe morphological gụnyere cell shrinkage, mfu nke intercellular adhesion, na apoptotic ozu, na-egosi na 5MQ na-ebute apoptosis, si otú ahụ na-egbochi mmụba cell [1]..
Iwu nke Gene metụtara na nkwupụta Protein: N'ịgbaso ọgwụgwọ 5MQ nke mkpụrụ ndụ HeLa, ọkwa mRNA nke ZEB1, SIRT1, na CD16 mụbara, ebe ọkwa TWIST na SERPIN1 mRNA belatara. N'otu oge ahụ, ngosipụta nke protein oncogenic phospho-Akt na SIRT1 belatara. Mkpụrụ ndụ ihe nketa na protein ndị a na-arụ ọrụ dị mkpa na tumorigenesis na ọganihu. Dịka ọmụmaatụ, TWIST na SERPIN1 na-ejikọta ya na mbuso agha na metastasis. Site n'ibelata okwu ha, 5MQ nwere ike igbochi ike mkpasu iwe na metastatic nke mkpụrụ ndụ HeLa. Ọ bụ ezie na ọkwa mRNA nke ZEB1 na SIRT1 mụbara, nkwupụta nke protein oncogenic SIRT1 belatara. Nke a nwere ike ime n'ihi na 5MQ na-emetụta ụkpụrụ post-transcriptional, na-egbochi ọrụ protein SIRT1 ma si otú ahụ na-emetụta mmụba cell na ndụ. Phosphorylated Akt na-arụ ọrụ dị mkpa na ndụ sel, mmụba, na nhazi usoro metabolic. Mbelata 5MQ n'okwu ya nwere ike igbochi mmụba cell cell na ndụ site na igbochi ụzọ mgbaàmà metụtara [1].
Gịnị bụ ngwa nke 5-Amino-1MQ?
Na nyocha ahụike nke metabolic, isi ọrụ ya bụ iweghachi nguzozi metabolic cellular site na igbochi NNMT. NNMT na-eri nicotinamide (onye na-ebute NAD⁺) ma na-emetụta methyl donor metabolism, ebe 5-Amino-1MQ na-egbochi usoro a: n'otu aka, ọ na-ebelata oriri nicotinamide methylation na adipocytes, na-ebuli ọkwa NAD intracellular intracellular iji rụọ ọrụ NAD⁺ na-adabere na ogologo ndụ ogologo ndụ, na-eme ka usoro SIRT. na-akwalite lipolysis, na-egbochi lipogenesis, na-enyere aka ịhazi metabolism ike na anụ ahụ adipose, ma na-ebelata oke abụba. N'aka nke ọzọ, ọ na-ebelata nguzogide insulin nke a na-ahụkarị na nsogbu metabolic site na imeziwanye mmetụta nke ụzọ insulin na-egosi, ebe ọ nwere ike na-achịkwa gluconeogenesis imeju na-enyere aka ịnọgide na-enwe ọkwa glucose ọbara kwụsiri ike. Ọzọkwa, a na-enyocha mmetụta ọ nwere na gut microbiota, yana ntule na ọ nwere ike ịkwado homeostasis metabolic n'ụzọ na-edoghị anya site na ịhazi ọrụ metabolic microbial (dịka ọmụmaatụ, ibelata mmepụta metabolite na-emerụ ahụ).
N'ime nchọpụta ọrịa kansa, ngwa ya na-elekwasị anya n'ịchụso 'nhụta metabolic' nke mkpụrụ ndụ etuto. Iji kwado mmụba ngwa ngwa, mkpụrụ ndụ tumor na-adaberekarị na ụzọ metabolic na-adịghị arụ ọrụ (dị ka mmetụta Warburg), na NNMT na-egosipụta nke ọma na ụfọdụ mkpụrụ ndụ tumo, na-akwado metabolism ha. Site na igbochi NNMT, 5-Amino-1MQ na-akpaghasị metabolism cell tumor n'ụzọ abụọ: Nke mbụ, ọ na-ebelata ọkwa NAD intracellular intracellular, na-emebi mmepụta ume, na-eduga n'inwe ike na-ezughị ezu na ihe ndị na-emepụta biosynthetic chọrọ maka mmụba; Nke abụọ, ọ na-emebi ojiji nke ndị na-enye onyinye methyl, na-akpaghasị usoro nhazi usoro epigenetic dị ka DNA methylation na mkpụrụ ndụ tumo, si otú a na-egbochi okwu mkpụrụ ndụ ihe nketa jikọtara ya na mmụba na metastasis. Ọzọkwa, ọ nwere ike na-egbochi uto tumor na-agbasa site n'ịgbanwe usoro metabolic na microenvironment tumor, na-enye ihe ndabere maka ịchọpụta usoro ntinye aka nke tumor metabolic.
Dị ka ngwá ọrụ nyocha bụ isi, ọ na-eje ozi dị ka isi ụzọ maka ịkọwapụta ọrụ physiological nke NNMT. Ndị na-eme nchọpụta nwere ike igbochi ọrụ NNMT kpọmkwem site na iji 5-Amino-1MQ na ụdị cellular ma ọ bụ anụmanụ iji hụ mgbanwe ndị na-esote na ihe ngosi metabolic. Dịka ọmụmaatụ, na nnwale cellular, nlekota NAD⁺ nleba anya, ọkwa onye inye onyinye methyl, na ọrụ nke enzymes na-etinye aka na fatty acid njikọ nwere ike ịkọwa ọrụ NNMT na-arụ na metabolism cellular. N'ụdị anụmanụ, jikọtara ya na nyocha ihe nlele nke anụ ahụ, ọ na-enyere aka ịchọpụta ọrụ NNMT kpọmkwem-dị ka mmetụta ya na metabolism imeju n'oge ịka nká ma ọ bụ nhazi nke ike na-enye ike na neurons. Ọzọkwa, itinye aka na nzaghachi dị iche iche n'ofe ahịrị sel (dịka ọmụmaatụ, mkpụrụ ndụ nkịtị na-egosi mmetụta dị ala yana nzaghachi a na-akpọ na mkpụrụ ndụ metabolic na-adịghị mma ma ọ bụ tumor) nwere ike inye aka n'ịchọpụta usoro metabolic cellular akọwapụtara, na-eduzi nyocha ezubere iche.
Na ngalaba nke ahụ ike na cognition nke anụ ahụ, ngwa ya gbadoro ụkwụ na njikọ 'metabolism ike - ọrụ cellular.' N'ime nyocha ahụike akwara, nrụzi akwara na-adabere na ịgbalite na mmụba nke sel satịlaịtị, usoro chọrọ inye ike zuru oke. -5-Amino-1MQ na-akwalite ọrụ satịlaịtị cell site na idowe ọkwa NAD intracellular n'ime sel akwara. N'otu oge ahụ, ọ na-ebuli ọrụ mitochondrial iji welie ike ike nke anụ ahụ, na-ebelata nchekasị mgbake mgbe mmerụ ahụ gasịrị. Ọ nwekwara ike ibelata nrụgide oxidative na anụ ahụ anụ ahụ, na-echebe mkpụrụ ndụ pụọ na mmebi nke ngwaahịa metabolic gabigara ókè kpatara. N'ime nyocha ọgụgụ isi, neurons ụbụrụ na-egosipụta ike dị elu nke ukwuu, yana mbelata ọkwa NAD⁺ jikọtara ya na mbelata ọrụ akwara. 5-Amino-1MQ na-echekwa nnyefe NAD neuronal neuronal site na igbochi NNMT, si otú a na-echekwa ọrụ mitochondrial na ibelata neuroinflammation. Ọ nwekwara ike imetụta metabolism nke neurotransmitter (site na enzymes dabere na NAD⁺ na-etinye aka na njikọ neurotransmitter) iji kwado ọrụ neuronal metụtara cognitive (dịka, ọrụ cellular na mpaghara mmụta / ebe nchekwa dị ka hippocampus), na-enye echiche ọhụụ maka nyocha mmezi ọrụ.
Mmechi
Dị ka onye na-egbochi nicotinamide N-methyltransferase (NNMT), 5-Amino-1MQ na-egosiputa uru bụ isi n'ofe ọtụtụ ngalaba site n'ịchụso ụzọ NNMT na-achịkwa usoro metabolic. Ọ nwere ike melite oke ibu na nguzogide insulin site na idowe ọkwa NAD⁺, na-ebuli ọrụ mitochondrial, na iweghachi nguzozi nke metabolic. Ọ na-elekwasịkwa anya adịghị ike nke metabolic na mkpụrụ ndụ tumo, na-akpaghasị mmepụta ume ha na usoro epigenetic iji gbochie uto tumor. Ọzọkwa, ọ na-eje ozi dị ka ngwá ọrụ nyocha maka ịkọwapụta ọrụ NNMT mgbe ọ na-egosipụta ọrụ ndị nwere ike ime n'ịrụzi ahụ ike na nhazi nke uche, na-enye ntụziaka ndị dị mkpa maka nchọpụta ntinye aka na ọrịa metabolic, ọrịa cancer, na ọnọdụ ndị metụtara ya.
Banyere Onye dere ya
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Onye ode akwụkwọ akụkọ sayensị
Akar s bụ onye nyocha nke ọrụ ya na-elekwasị anya na usoro mkpụrụ ndụ na usoro ọgwụgwọ. O nyela aka na ọmụmụ ihe na-enyocha ọrụ nke enzymes na obere ihe mgbochi molecule n'ịchịkwa mmụba nke cellular. Nchoputa ya na-emesi ike mkpa ọ dị ịchụ n'okporo ụzọ metabolic, dị ka nicotinamide N-methyltransferase, iji chọpụta usoro ọhụrụ nke biomedical. Akar s depụtara na ntụaka nke ntụaka [2].
