Te kikorangi metilīni me ngā huarahi NAD+: ngā tikanga mahi, ngā taunakitanga, me ngā kerēme mō te whakakotahi

Ka whakamāramatia te kikorangi metilīni me ngā tāpiringa e hokona ana hei kaiwhakapiki NAD+ mā ngā kupu mitokōria me te pūngao pūtau. Kāore tētahi o aua whakamārama e whakaatu ana he aha tā te hua e mahi ai.

Ka pā ngā huarahi e rua ki ngā taurangi rerekē. Ka ngana tētahi ki te whakarerekē i te nui o te NAD+ i roto i ō pūtau. Ka whakarerekē tērā atu i te ōwehenga o ōna āhua e rua. Ehara ēnei i ngā ara e rua ki te wāhi kotahi.

E rua ngā rahinga ka rangiruatia tonutia

He whākōkī āpiti te NAD+. Ka tango ia i tētahi takirua irahiko, i te āhua o tētahi katote hydride, ā, ka huri hei NADH. Ina tukuna atu e te NADH aua irahiko, ka huri anō hei NAD+. Ka whakamahia tonutia tēnei huringa e ngā pūtau: mā konei ka tae te pūngao i tangohia mai i te kai ki ngā pūnaha pūmua e hanga ana i te ATP.

Nā te mea he āhua e rua te NAD+ me te NADH o te rāpoi ngota kotahi, e rua ngā rahinga motuhake i roto i te pūtau e tika ana kia aroturukihia. Ko te tuatahi, ko te tapeke: te nui o te NAD+ me te NADH ina huihuia. Ko te tuarua, ko te ōwehenga i waenga i aua mea, e whakaatu ana i te nui o ngā irahiko e kawea ana e ngā kaikawe irahiko i taua wā.

Mā tētahi puna wai e mārama ai te rerekētanga. Ko te rōrahi wai kei muri i te pāpuni te tapeke. Ko te wehenga i waenga i te wai e puritia ana ki runga me te wai e tukuna ana ki raro te ōwehenga. Mā te whakatuwhera i tētahi kūaha ka taea te whakapiki i taua ōwehenga me te kore e tāpiri i te rita kotahi. Ehara tēnei i te kupu whakarite mō te mahi a te kikorangi metilīni. He tata kē ki te whakamārama tōtika.

Te huarahi whakarato

He rauemi hanga ngā tāpiringa matū tīmatanga NAD+, tae atu ki te nicotinamide riboside, te nicotinamide mononucleotide, me te nicotinamide. Ka hangaia e ngā pūtau te NAD+ mā tētahi ara hangarua e kīia ana ko te ara whakaora, ā, ka uru ngā matū tīmatanga ki taua ara. Ko te whāinga, kia nui ake te tapeke.

Kua tino whakapūmautia tēnei i ngā kararehe: i roto i ngā tauira maha, ka heke te NAD+ kiko i te kaumātuatanga me ngā mate pākia, ā, ko te whāngai matū tīmatanga ka whakapiki i taua rahinga i te nuinga o te wā. I ngā tāngata, he whāiti ake ngā kitenga. E whakaatu ana ngā whakamātautau tangata ka whakapiki ēnei matū i ngā taumata NAD+ toto e inea ana. Ko te mea kāore anō kia puta, he whakapainga pūmau i tētahi putanga haumanu, arā, ngā mea ka kitea e te tangata, ngā mea rānei i hoahoatia te whakamātautau hei ine.

Ko te kōrero "I piki ngā taumata NAD+" he ine i tētahi mea i roto i te tinana. Ehara i te kitenga mō te āhua o te tangata, mō tōna neke, mō tōna whakaora rānei.

Te mahi kē a te kikorangi metilīni

Ehara te kikorangi metilīni i te matū tīmatanga. He waikano whakahāora-whakaheke, kua whakamahia ki te rongoā mō neke atu i te kotahi rau tau, ā, he whāiti ake ōna whakamahinga kua whakamanatia i ōna whakamahinga e rangahautia ana.

I roto i te pūtau, ka whakahekea e ngā whākōkī e whakawhirinaki ana ki te flavin ki tētahi āhua kore tae, arā, te leucomethylene blue, kātahi ka whakahāoratia anō. Ka taea ngā irahiko me haere mā te matatini I, te teihana tuatahi o te mekameka hā pūtau, te tuku kē mai i te NADH mā te kikorangi metilīni. Ka huri te NADH hei NAD+.

Ka piki te ōwehenga. Kāore e nui ake te tapeke.

I ine tika tētahi rangahau kiore mō te manawa mate huka i tēnei i roto i ngā mitokōria manawa kua wehea. Nā te tāpiri kikorangi metilīni ki ngā kukūtanga mai i te 6 ki te 18 micromolar i te wā o te whakahāora waikawa ngako, ka heke te NADH me te ōwehenga NADH-ki-NAD+ i runga i te nui i tāpirihia. He iti noa iho te panoni o te rahinga tūturu o te NAD+ i tō te NADH. Koinei te mea ka tūmanakohia i tētahi matū e huri ana i tētahi āhua hei tērā atu, kaua e hanga i te rahinga tāpiri o tētahi o aua āhua.

He mea nui te wāhi ka tae atu aua irahiko. I roto i ngā mitokōria roro kua wehea, nā te kikorangi metilīni i te 100 nanomolar ki te 1 micromolar i whakapai ake te hanga pūngao i te wā i aukatia ai te mekameka hā pūtau. I taua wā tonu, i whakapiki hoki i te hanga hauwai perōkai, me te whakaiti i tōna whakakorenga, i roto i ia āhuatanga i whakamātauria. E ai ki ngā kaituhi, i ahu mai te hauwai perōkai i te whakahekenga hāngai o te hāora e te kikorangi metilīni kua whakahekea. Kāore ngā irahiko ka puta i te NADH mā tēnei ara e ngaro. Ka tae atu ki te hāora.

Ka āta whakapuaki tētahi rangahau motuhake ki te kiko uaua here Achilles i tēnei take. I whakahoki te kikorangi metilīni i te taurite NAD+/NADH, ā, i whakapiki i te hanga ATP i ngā pūtau uaua here kua whara me tētahi tauira mate uaua here kiore. E tuhia ana hoki i te pepa rangahau kāore he panoni nui ā-tatauranga i te tapeke NAD.

Ngā mea ka whakapūmautia e ngā whakamātautau kiko me ngā kararehe

E whā ngā whakamātautau puta noa i ngā tekau tau e whā e whai ana i te whakaaro kotahi, ā, e whakaatu tonu ana i tōna rohenga.

I te whāngai waipiro wā roa ki ngā kiore, i whakaheke te ethanol i ngā ōwehenga NAD+/NADH o te wai pūtau me ngā mitokōria i roto i te ate. Nā te tāpiri kikorangi metilīni ki te kai i ārai te nuinga o taua panoni. Kāore i whakaiti i te whakangako o te ate nā te ethanol. Ko te whakatika i te ōwehenga kāore i whakatika i te putanga. He mea tika kia maumahara ki taua kitenga o 1985 i mua i tētahi kerēme ko te panoni whakahāora-whakaheke te tikanga mahi e hua ai tētahi painga.

I roto i ngā pūtau ate me ngā kiore e kai ana i te kai nui te ngako, i whakapiki te kikorangi metilīni i te ōwehenga NAD+/NADH, i whakapiki i te SIRT1, i whakaiti i te tāpiringa rōpū acetyl ki te PGC-1alpha, i whakahohe i te AMPK, ā, i whakaiti i te whakaeminga ngako i te ate. I konei, i panoni tahi te putanga me te ōwehenga. E whakaatu ana taua pepa rangahau kāore te pānga e neke tonu i te ahunga kotahi: he pai ake te whakapiki i te rahinga DNA mitokōria mā te toru milligrams per kilogram per day i te tekau, engari i piki te whakamahinga hāora me ngā tohu AMPK i te pikinga o te nui i tukuna.

I roto i te manawa mate huka, nā te kikorangi metilīni i tukuna ki te wai inu mō ngā wiki tekau mā tahi i whakaheke te ōwehenga NADH-ki-NAD+ i roto i ngā mitokōria manawa, ā, i whakapiki i te mahi a te sirtuin 3. I heke te tāpiringa rōpū acetyl ki te lysine i ngā wāhi 83 puta noa i ngā pūmua 34, ko te nuinga i te kawe me te whakahāora waikawa ngako. I pai ake te hautanga toto i panaia e te manawa. Engari kāore i whakatikaina te hā pūtau e tautokona ana e te matatini I. Nā tētahi whakamātautau whakakore ira i wehe ngā pānga e rua ka māmā te whakahanumi: ko te nuinga o te panoni ōwehenga i puta me te kore sirtuin 3, engari i whakawhirinaki te tangohanga rōpū acetyl ki taua whākōkī.

I roto i te rangahau uaua here, i whakamahia te kikorangi metilīni i te wā i aukatia ā-matū ai te matatini I ki te rotenone. I whakahoki tonu i te taurite NAD+, engari kāore tonu i ārai i te ahotea whakahāora, i te paheketanga o te kopu kiko, me te ngaronga o te oranga pūtau. Kāore te whakahoki i te ōwehenga i ranea kia ora anō te kiko.

Ka whakamahi tētahi pepa ka taea te tā me ngā tohutoro katoa i aua haupae anō.

Te take ka uru ngā sirtuin ki te tautohe

Ka tango ngā sirtuin i ngā rōpū acetyl mai i ngā pūmua, ā, ka whakapau i te NAD+ hei mahi i tērā. Ka urupare tō rātou mahi ki te wāteatanga o te NAD+. Nō reira, ko tētahi matū e whakarerekē ana i taua wāteatanga ka whakarerekē hoki i te mahi a ngā sirtuin i muri mai.

Koinei te pūtake o te nuinga o ngā hokohoko "kikorangi metilīni mō te NAD+". Koinei hoki te wāhi e hē ai te arorau. Ka taea e te panoni ōwehenga te whakapiki i te mahi a ngā sirtuin. Kāore tēnei e tohu ana ka whakarato te hua i te NAD+, ā, kāore hoki e tohu ana he ōrite te pānga ki te tango matū tīmatanga. He take tō te whakamāoritanga whakahāora-whakaheke o ēnei inenga hei tūpato, ā, he mea tika kia pānuihia i mua i te whakaae ki tētahi o aua whakamārama.

Ngā mea kua whakamātauria ki te tangata

Kua whakamahia haumanu te kikorangi metilīni mō ngā tekau tau i ngā āhuatanga whakapeka e aroturukihia ana: te methemoglobinemia, te tāoke ki te pūnaha io e pā ana ki te ifosfamide, me te pēhanga toto tino iti i te wā o te pokanga. He whakamahinga whāiti ēnei, kei raro i te tirotiro ngaio, ehara i te taunakitanga mō te tango mā te waha ia rā hei āwhina i te āheinga mahi.

Kāore ngā rapunga mō tēnei tuhinga i kitea he rangahau tangata e ine ana i ngā hua pākia NAD+ i muri i te tuku kikorangi metilīni ki ngā kaitūao hauora. I ahu mai ngā kitenga i runga ake nei i ngā mitokōria kua wehea, i ngā pūtau kua whakatipuria, i te kiko kiore, me ngā kiko kua tangohia mai i te tangata. He pikinga whai take te uaua here kua tangohia, ka puritia kia ora i roto i tētahi ipu, i tētahi aho pūtau. Engari ehara tonu i te tangata.

He rangahau tangata tūturu kei roto i ngā tuhinga mō ngā matū tīmatanga, ā, he iti noa ngā hua. Ka piki te NAD+ toto. He rerekē ngā putanga haumanu, ā, he iti te nuinga.

Nō reira he pātai tika te kerēme mō te whakakotahi, engari kāore i te tino makona te whakautu: kāore tētahi rangahau kua whakaputaina, tētahi whakamātautau, tētahi raupapa take haumanu rānei i kitea mō tēnei tuhinga i whakamātautau i te kikorangi metilīni me te nicotinamide riboside, te nicotinamide mononucleotide, tētahi whaowhia NAD+ rānei kia kotahi. Ko te tangata e kī ana he tautoko mō te whakakotahitanga, he pānga whakapakari tahi rānei, kei te whakawhānui i ngā whakatau mai i ngā huinga taunakitanga motuhake e rua.

Ka taea te hē o taua whakawhānuitanga i ngā ahunga e rua. Ka nui rawa pea te tūmanako, mēnā kāore rawa te tapeke i te taurangi whakawhāiti i muri i te whakahokinga o te ōwehenga. Ka māmā rawa hoki pea te whakamārama, nā te mea ka huri te ahunga o te urupare a te kikorangi metilīni ki te nui ka tukuna. Ka whakamārama ōna ake kairangahau i te matū hei matū hormetic: ka pai ake te whakaheke i ngā kukūtanga iti, engari ka whakawhiti ngā kukūtanga nui i ngā irahiko kia wehe atu i te mekameka hā pūtau, ā, ka taea te mahi hei kaiwhakatairanga whakahāora. Kāore te tāpiri rauemi tauhohenga e haumaru ake ai taua ānau.

He āwangawanga pāhekoheko hoki kāore e pā ana ki te NAD+. Ka aukati te kikorangi metilīni i te monoamine oxidase A. Nā tēnei ka whai mōrea e pā ana ki te serotonin ina whakamahia me ētahi rongoā whakahē pāpōuri; i kitea e tētahi arotake o te tāoke ki te pūnaha io matua kua pūrongotia i tutuki ngā paearu Hunter mō te tāoke serotonin i ngā take 13 o te 14. Ka taea hoki te whakatupu methemoglobinemia i te pānga nui. Mēnā ka tango koe i te rongoā whakahaunga, ko te pātai mō te whakakotahi hei tuku ki tō mātanga haumanu e pā ana ki aua ara, kaua ki te taurite whakahāora-whakaheke. Ka hāngai taua āta whakaaro ki ngā whakakotahitanga noa hoki: he huinga taunakitanga motuhake mō ētahi atu tāpiringa ka tangohia me te kikorangi metilīni, ā, kāore anō te nuinga kia whakamātauria.

Te take ka whakatauhia e te parakore ko tēhea whakamātautau e whakahaerehia ana e koe

He ranunga te hua kikorangi metilīni kia whakapūmautia rā anō e tētahi taiwhanga he rerekē. Ko te poke whai take i konei ko Azure B, he phenothiazine kua tangohia tētahi rōpū methyl, ā, ehara i te matū kore mahi. He waikano whai mahi whakahāora-whakaheke e whai ana i taua matūhiko taketake anō. Nō reira, ko te hua e mau ana i te rahinga whai take o Azure B ehara i te putanga parakore ake, poke ake rānei o taua maimoatanga kotahi. He ranunga rerekē e mahi ana ki taua ara kotahi, i tētahi ōwehenga kāore anō kia tautuhia e tētahi.

Mā te kōeke USP ka whiwhi te kaihoko i tētahi matū kua āta tautuhia. Ko te hua kāore i te kōeke USP, ko te mea pea he waikano kōeke pueru. He poke kei ngā kōeke pueru e kore ai e tika hei kai mā te tangata, tae atu ki ngā konganuku taumaha me ngā toenga whakarewa.

Ehara te āputa i waenga anake i ngā kōeke. He maha ngā kaihoko e kerēme ana ka ū ki te USP, engari ka whakamātautau mō ngā konganuku taumaha anake, kātahi ka whakaatu i taua huinga whakamātautau kotahi hei ūnga katoa. Ka kapi i te whakaritenga katoa te tuakiri, te parakore, ngā poke waro, ngā toenga whakarewa, ngā poke huānga, te toenga i muri i te tahunga, ngā paepae moroiti, me ngā endotoxin huakita. Kāore tētahi huinga whakamātautau wāhanga e taea te whakatau i ngā mea ka waiho atu e ia. Kei roto i ngā mea kua waiho atu ngā matū whanaunga me ngā toenga whakarewa.

Ka hoko a Blupreme i te kikorangi metilīni mai i tētahi kaihanga rongoā, ā, ka whakaputa i tētahi tiwhikete tātaritanga e kapi ana i te whakaritenga katoa. Nā reira, ko te matū kei roto i te pounamu ko te matū e whakamāramatia ana e te rangahau. Ki te hiahia koe ki te arowhai i te arorau i mua i te hoko, ka whakamārama te pānui rangahau kikorangi metilīni i ngā mea ka taea, kāore hoki e taea, e ia momo rangahau te whakaatu.

Te rerekētanga ka mau tonu i raro i te āta tirotiro

Ka whakarerekē te tāpiri matū tīmatanga NAD+ i te nui o te NAD+ kei reira. Ka whakarerekē te kikorangi metilīni i te mahi a te NAD+ kei reira kē. Ko te tuatahi he pātai whakarato, ko te tuarua he pātai mō te rere. He iti noa te kōrero a ngā whakamātautau e tautoko ana i tētahi mō tērā atu.

Ko te tautoko mō te kikorangi metilīni he tikanga mahi tuitui, kua whakapūmautia i ngā mitokōria kua wehea me te kiko kararehe, me tētahi herenga mārama ka puta tonu: ehara te panoni ōwehenga i te mea ōrite ki te whakatika i te kiko. Ko te mea e ngaro ana, ko ngā whakamātautau tangata e ine ana i te pānga NAD+ ki te tangata. Ko te mea kāore i tētahi o ngā kāwai, he whakamātautau hāngai o ngā mea e rua ka tangohia tahitia.

Me ōrite te āta tirotiro i ngā kāwai e rua. Pātaihia ko tēhea taurangi e kerēmetia ana ka whakarerekētia e te hua, kātahi ka pātai ko ēhea inenga mō taua taurangi kei te wātea i te tangata. Ina ko te whakautu he rangahau pūtau, he kiore, he ara rānei e whai take ana i runga i te arorau, koirā tonu tōna āhua. Ehara i te huinga tāpiringa kua whakamātauria.