Gabatarwa zuwa NMN (Nicotinamide Mononucleotide)

2023-08-12 14:22:53

Cikakken sunan NMN shine nicotinamide mononucleotide, wanda shine nicotinamide mononucleotide, wanda shine nucleotide mai aiki na halitta ta halitta. NMN yana da nau'i biyu marasa tsari, α da β; β isomer shine nau'i mai aiki na NMN, kuma nauyin kwayoyin sa shine 334.221 g / mol.

Hoto: Tsarin tsari na sinadarai da ƙirar ball-da-stick na NMN

Tebur: Tsarin sinadarai na NMN
Kaddarorin jiki da sinadarai na NMN

Bayanai daga PUBCHEM

Tushen Abinci na NMN

An rarraba NMN a cikin abinci na yau da kullum, kayan lambu irin su farin kabeji (0.25-1.12 mg NMN / 100 gm) da kabeji na kasar Sin (0.0-0.90 mg NMN / 100 gm), 'ya'yan itatuwa irin su avocado (0.36-1.60 mg NMN / 100 gm) , Tumatir (0.26-0.30 mg NMN / 100 gm), nama irin su danyen naman sa (0.06-0.42 mg NMN / 100 gm) suna da wadata a cikin NMN [1].

Ƙaddamarwa na NMN

Ɗaya daga cikin kwayoyin nicotinamide da kwayoyin guda ɗaya na 5-phosphoribosyl-1-pyrophosphate (PRPP) ana yin su ta hanyar nicotinamide phosphoribosyltransferase (NAMPT ko NAMPRT) don samar da kwayoyin NMN guda daya da kwayoyin pyrophosphate (PPi). Baya ga nicotinamide, ana iya samar da NMN, kuma kwayar nicotinamide riboside (NR) guda ɗaya ta ƙunshi phosphorylated ƙarƙashin catalysis na nicotinamide riboside kinase (NRK) don samar da kwayoyin guda ɗaya na NMN.

Ƙayyadaddun nama na NMN synthetase, cinye enzyme

(1) NAMPT: NAMPT yana ko'ina a cikin jiki, amma akwai manyan bambance-bambance a cikin matakan magana tsakanin kyallen takarda. A cikin kwakwalwa da zuciya, hanyar ceton da ke dogara da NAMPT shine yanayin da aka fi so na samar da NAD +; yayin da ke cikin ƙwayar ƙwanƙwasa, hanyar hanyar ceton da ke dogara da NRK shine yanayin da aka fi so na samar da NAD +.

(2) NMNATs (NMN-cinyewar enzymes): Ƙwararrun ƙwayoyin linzamin kwamfuta na rayuwa sun nuna cewa ayyukan NMNAT subtypes sun fi girma fiye da na NAMPT, kuma aikin NMNAT subtypes ba a iyakance a mafi yawan kyallen takarda ba sai jini.

(3) NRKs: Binciken maganganu na NRK subtypes ya nuna cewa NRK1 yana cikin ko'ina, yayin da NRK2 ya fi girma a cikin ƙwayar kwarangwal. Daidai da wannan, kari na NR na yau da kullun ya haifar da haɓaka matakan NAD + a cikin tsoka amma yana da ɗan tasiri a cikin kwakwalwa ko farin adipose nama [2].

Farashin NMN

Hanyoyi daban-daban don NMN don shiga sel

NMN yana da jigilar membrane a saman wasu sel, wanda zai iya canja wurin NMN kai tsaye zuwa cikin tantanin halitta, don haka akwai hanyoyi guda biyu don NMN don shiga tantanin halitta:

① Kai tsaye shiga cikin sel ta hanyar masu jigilar kaya: A farkon 2019, takarda ta yanayi metabolism ta tabbatar da wannan ra'ayin. Labarin ya gano cewa akwai wani nau'in jigilar NMN a cikin ƙananan hanji na beraye, wanda ake kira Slc12a8, wanda shine amino acid da polyamine transporter. Yana da babban zaɓi zuwa NMN kuma baya jigilar NaMN, wanda yayi kama da tsarin NMN[3].

② Dephosphorylation na CD73 akan fuskar tantanin halitta zuwa NR (ta hanyar ma'auni na nucleoside transporter ENTs) a cikin tantanin halitta, sa'an nan kuma ta hanyar NRK enzyme a cikin cytoplasm zuwa NMN, ya shiga cikin mitochondria kuma ana amfani dashi (mitochondion ba tare da NRK) [4] .

NAM ba kawai shine farkon NMN ba, har ma samfurin NAD + hydrolyzed ta CD38, wanda aikin NADAse ya ƙare. Saboda haka, kira, amfani da sabuntawa na NAD + shine sake zagayowar da ke tattare da intracellular da NMN/NR → NAD+ → NAM → NMN.

Haɓaka NAD+ ta baka NMN

NMN shine farkon NAD +, kuma aikinta yana nunawa ta NAD+ (nicotinamide adenine dinucleotide).

A cikin hanyar hanyar ceto, nicotinamide riboside (NR) ko nicotinamide (NAM) sun haɗa nicotinamide mononucleotide (NMN) ta hanyar NRK (nicotinamide riboside kinase) ko NAMPT, NMNAT, da NMN suna hada NAD + ta hanyar NMNAT1-3 enzymes.

PNP: purine nucleoside phosphorylase; NRK: nicotinamide riboside kinase; QPRT: quinolinic acid phosphoribosyltransferase NAPRT: nicotinic acid phosphoribosyltransferase; NAMPT: nicotinamide phosphoribosyltransferase; NMNAT: nicotinamide mononuclear adenylate adenylyltransferase

Kodayake ba za a iya gano cikakken tsarin NMN a cikin maganin ba, gudanar da baki na NMN na iya har yanzu da sauri (15min) yana haɓaka matakan NAD + na mice da mata [5]:

Hanta, pancreas, farin adipose nama NMN, matakan NAD+

Matsayin NMN

NMN galibi yana taka rawa ta hanyar juyawa zuwa NAD+. NAD + kuma ana kiranta da coenzyme I, kuma cikakken sunanta shine nicotinamide adenine dinucleotide. An rarraba shi sosai a cikin dukkanin sel na jikin mutum kuma yana shiga cikin dubban halayen biocatalytic. Yana da mahimmancin coenzyme a jikin mutum. .

Ragewar NAD + a lokacin tsufa ana ɗaukar babban dalilin cuta da nakasa, kamar ji da hangen nesa, fahimi da rashin ƙarfi na motsa jiki, ƙarancin rigakafi, cututtukan arthritis saboda dysregulated autoimmune kumburi martani, cuta na rayuwa, da cututtukan zuciya.

Sabili da haka, ƙarin NMN yana ƙaruwa da abun ciki na NAD + a cikin jiki, ta haka jinkirtawa, ingantawa, da kuma hana nau'o'in abubuwan da suka shafi tsufa, ko cututtuka na rayuwa da suka haifar da shekaru da cututtuka na tsofaffi.

A. NAD+ da circadian rhythm

NAD +-dogara deacetylase SIRT1 yana aiki azaman gada tsakanin rhythm na circadian da metabolism ta hanyar haɗa madaidaicin amsawar enzymatic wanda ke daidaita hanyar ceton NAD + da madauki na fassarar circadian-fassara madauki.

NAD+ tana sarrafa agogon halitta ta hanyar SIRT1. SIRT1 deacetylates BMAL1 da PER2, wanda ke gaba da aikin acetylation na CLOCK, don haka SIRT1 na iya hana rubutun kwayoyin halittar agogo wanda CLOCK-BMAL1 ke shiga tsakani. Sabili da haka, NAD + yana rinjayar aikin deacetylation na SIRT1 ta hanyar nasa matakin, wanda hakan yana rinjayar bayyanar da jerin sunadaran da ke da alaƙa da agogo ciki har da NAMPT [6].

Tsarin agogon halitta yana da alaƙa da cututtuka da yawa, gami da amma ba'a iyakance ga matsalar barci ba, ciwon sukari, da ciwace-ciwace. Yawancin hanyoyin cututtuka suna haifar da rikicewar agogon circadian, wanda zai iya fitowa daga kwayoyin halitta ko muhalli. Gabaɗaya, kiyaye agogon circadian aiki kullum yana taka muhimmiyar rawa wajen kiyaye lafiya.

B. NAD + da tsarin juyayi

Sirtuins sune nicotinamide adenine dinucleotide (NAD+) -dogara deacylases na al'ada da ke da alaƙa da ƙuntatawar caloric da tsufa a cikin dabbobi masu shayarwa. Wadannan sunadaran kuma suna taka muhimmiyar rawa wajen kiyaye lafiyar neurons a lokacin.