Te kahurangi metilīni me te NAD+/NADH: te whakamāori i te taurite hāora-whakaheke o te pūtau

He maha ngā pūrongo mō te kahurangi metilīni me te NAD+ ka whakakotahi i ngā whakapae rerekē e toru hei whakapae kotahi. Ko te whakapae tuatahi, i neke te ōwehenga NAD+ ki te NADH ki te āhua whakahāoratia. Ko te tuarua, he nui ake te NAD tapeke kei roto i te pūtau. Ko te tuatoru, i hoki mai te whakaputanga pūngao. Ki te whakarongo atu, he kōrero kotahi ēnei mō te whakaora i te pākia. I ngā whakamātautau, he maha ngā wā ka wehe kē ēnei hua, ā, ko ngā hua tino whai take ko ngā āhuatanga tonu e rerekē ai.

E mārama ana te take o tēnei rangirua, nā te mea he ōrite te kupu kōrero mō ēnei rahinga e toru. Ka tango te NAD+ i ngā irahiko i roto i ngā tauhohenga pākia, ka huri hei NADH. Kātahi ka whakahāoratia anō e ngā mitokōria te NADH hei NAD+ i te matatini I, ka whakamahi hoki i te pūngao ka tukuna hei whakahaere i te hanga ATP. Kei te whakamārama mō te kawe irahiko i ngā mitokōria he kōrero whānui ake mō taua ara irahiko, ā, kei te ATP me te pākia pūngao ngā kōrero mō te taha pūngao. Engari, he mea rerekē te ōwehenga me te puna. Ka whakaatu te ōwehenga i te tohatoha o ngā rāpoi kaikawe e noho kē ana, i waenga i ngā āhua kua utaina me ngā āhua kāore anō kia utaina. Ka whakaatu te puna i te maha katoa o ngā rāpoi kaikawe. Ki te pai ake te ōwehenga, engari he ōrite tonu te puna, he tohatoha anō tēnā, ehara i te hanga rāpoi hou.

E rua ngā wāhanga, e rua ngā tohu ine

Tērā anō tētahi rerekētanga e puta ai ngā hē whakamāori kāore e tino kitea. Ko te nuinga o ngā puna NAD o te wai pūtau me ngā mitokōria ka wehea e te kiriuhi o roto o te mitokōria. Nā reira, ka taea e ia wāhanga te noho ki tētahi āhua whakahāoratia ake, whakahekea ake rānei, motuhake i tērā atu. Ka hunaia tēnei e tētahi tau kotahi mō te pūtau katoa.

Nā ngā rangahau ate i taea ai te ine i tēnei wehenga wāhanga. Ka whakaatu te taurite lactate ki te pyruvate i te ōwehenga NAD+ ki te NADH o te wai pūtau, nā te mea ka tūhono te whākōkī lactate dehydrogenase i aua takirua e rua. Ka whakaatu te taurite 3-hydroxybutyrate ki te acetoacetate i te ōwehenga o ngā mitokōria mā tētahi tūhononga ōrite. Ina inea ngā takirua e rua i te kiko kua rawhi-whakatiohia, pērā i te rangahau whāngai ewaro mō te wā roa ki ngā kiore, ka puta ngā inenga hāora-whakaheke e rua mai i te ate kotahi. Ka taea hoki e tētahi pūhui te neke i tētahi inenga nui ake i tērā atu.

Ka mahi te kahurangi metilīni i tēnei pūnaha hei kaikawe irahiko, kaua hei wahie. Ka tango i ngā irahiko mai i te NADH e tata ana ki te matatini I, ka whakahekea, kātahi ka tuku atu i aua irahiko ki ngā kaikawe kei muri i te ara, pērā i te cytochrome c. Ko te hua katoa, ka whakahāoratia te NADH me te kore e haere mā te ara noa katoa. Ka whakamārama tēnei tikanga mahi i tōna painga me tōna herenga: ka taea e ia te whakamauru i te aukatinga nā te nui rawa o te āhua whakahekea, engari kāore e hanga anō i tētahi matatini kua pakaru, e hanga rānei i ngā rāpoi NAD hou.

E rima ngā rangahau, kotahi te tauira o ngā hua wehe kē

Ka whakarārangi te ripanga i raro nei i ngā rangahau e rima mā te kiko, te putanga hāora-whakaheke, te putanga pūngao, me ngā mea i tino hoki mai. Pānuitia ngā tīwae whakamutunga e rua hei takirua. Ko taua hononga te kaupapa o tēnei tuhinga.

Ngā wāhi kāore te whakatikatika hāora-whakaheke i whakaora i te kiko

Ko te rangahau tawhito rawa o tēnei kohinga tonu te whakatūpato tino mārama. I ngā kiore i whāngaihia ki te ewaro hei 36 ōrau o te pūngao, i heke ngā ōwehenga NAD+/NADH o te wai pūtau me ngā mitokōria, i inea mā ngā takirua tohu e rua. Nā te kahurangi metilīni i roto i te kai, tata ki te 42 mg mō ia kg ia rā, i ārai te nuinga o aua huringa. Heoi, i te wā ine tōmuri, tata ki te toru whakareatanga te pikinga o te triacylglycerol ate, ahakoa i reira te waikano, kāore rānei. I whakaatu hoki te tirohanga kiko i te ngako ōrite ki te pokapū o ngā kōpuku ate. I whakapuaki tika ngā kaituhi i te whakataunga uaua: ehara ko te huringa hāora-whakaheke e haere tahi ana me te whakahāoratanga ewaro, ko ia anake, te take e puta ai te ate ngako. Ki te whakaarotia e te kaipānui ko te whakatikatika ōwehenga he whakatikatika whēkau, ka hē tana pūrongo mō tēnei pepa. Kei te rangahau ate me te ewaro te hoahoa katoa, tae atu ki ngā rōpū whakatairite i whāngaihia ki te rahinga kai ōrite me te tango tauira i waenganui pō i te wā tino kaha o te haurangi.

Whakatauritea ki te rangahau ate mō te kai nui te ngako, i reira i haere tahi ai taua momo huringa ōwehenga me te tino pai ake o te kiko. I ngā pūtau ate, ā, i te ate o ngā kiore iti whai muri i te tuku mā te waha, i whakapiki te kahurangi metilīni i te ōwehenga NAD+/NADH. I whaihia hoki te mekameka tuku tohu, tētahi taahiraa ki tētahi: i piki te SIRT1, i tangohia ngā rōpū acetyl i te PGC-1alpha, i piki ngā tohu hanga mitokōria me te kohi hāora, kātahi ka whakahohea te AMPK, te CPT-1 me te PPARalpha. I whakaaturia hoki te whakawhirinaki o te whakahohe AMPK ki te SIRT1. He iti ake te ngako i whakaemihia ki te ate o ngā kiore iti whai kai nui te ngako. Ko te whakamārama i whakatakotoria, nā te huringa hāora-whakaheke i konei i whakatuwhera tētahi ara whakahaere ira, kaua ko te whakataurite anō noa i te matū, e whakamāramatia ana i te rangahau ate mō te SIRT1 me te AMPK. He momo inenga ōrite ki tō te rangahau ewaro, engari he hua kiko tauaro. Ko te rerekētanga kei te ara ka whai mai, kāore i te ōwehenga anake.

Te manawa me te etine: ngā sirtuin, te tāpiri acetyl, me te whakaoranga kāore he whakaoranga ATP

Ka tūhono te rangahau manawa mate huka i te huringa hāora-whakaheke ki te tāpiri rōpū acetyl ki ngā pūmua mā tētahi sirtuin rerekē. He nui rawa te tāpiri acetyl ki te lysine i runga i ngā whākōkī pākia o ngā mitokōria mate huka, ā, ka haere tahi tēnei me te kore ngāwari ki te huri i ngā matū tīmatanga ka whakamahia. Nā te kahurangi metilīni i te 10 mg mō ia kg ia rā i pai ake ai te whakahāoratanga NADH. I ngā mitokōria kua wehea, i whakawhirinaki taua pānga ki te horopeta puta noa i te 6 ki te 18 micromolar. I whakapiki hoki i te hohe o te SIRT3, i whakaheke whānui i te tāpiri acetyl, ā, i pai ake ngā rōrahi manawa me te hautanga pana toto, ahakoa i mau tonu te ngoikoretanga taketake o te matatini I. E mārama ana te pepa mō te whanonga horopeta i ētahi atu tuhinga rangahau: ka tautoko ngā kukū iti i te mahi kaikawe i te āhua whakahekea, engari ka taea e ngā kukū nui ake te whakawhiti i ngā irahiko ki ngā ara kāore he hua. Nō reira, he pānga hormesis, he rerekē te urupare i ngā taumata iti me ngā taumata nui, kaua he pānga ka piki, ka heke rānei i te ahunga kotahi puta noa. Kei te rangahau tāpiri acetyl mō te manawa mate huka te rangahau whānui o ngā pūmua me ngā inenga manawa. Kei te ahotea whakahāora me te whakahaere ROS te whakamārama ahotea whakahāora e tūāpapa ana i tēnei.

Ka tino wehe kē ngā hua i te rangahau etine. I ngā kiore iti Harlequin hapa AIF, he hapa hanga matatini I, i tiakina e te kahurangi metilīni te mātotoru o te etine, ngā wāhanga o waho o ngā pūoko mārama, me ngā tohu mō ngā pūtau rākau, ngā pūtau koeko, ngā pūtau Muller me ngā pūtau ganglion. I ngā pūtau pūoko mārama 661W i pāngia ki te rotenone, i whakahoki te waikano i te ōwehenga NADH ki te NAD+ ki te āhua noa, i whakaheke hoki i ngā momo hāora tauhohe i te 15 micromolar. Heoi, i noho iti tonu te ATP i ngā kukū i whakatairanga i te oranga. I tiakina te hanganga me te oranga me te kore e whakaora i te pūngao, ā, i marino ake hoki te urupare mitokōria ki ngā pūmua kāore anō kia whātuituia me te tukanga whakakore mitokōria. Nā taua hua ka mārama ake te mahi a te waikano hei whakamauru i te ahotea whakaheke me te ahotea whakahāora, kaua hei whakahoki pūngao, e tuhia ana i te rangahau tiaki pūoko mārama o te etine.

Te uaua here: te whakamātautau i panoni ai te matū engari kāore te kiko i pai ake

Kei roto i te rangahau uaua here Achilles ngā tauira e rua i te pepa kotahi, ā, me āta pānui. Kei te tātaritanga 2026 mō te mate uaua here Achilles te whakamārama katoa mō ia peka whakamātautau. I kitea i te uaua here māuiui te mimiti o te NAD+, te iti o te ōwehenga NAD+ ki te NADH, ngā tohu ngoikore o te matatini I, te iti o te ATP, me te collagen kua raruraru tōna hanganga. I whakahoki te kahurangi metilīni i te matū NAD me te ATP, i whakapai hoki i ngā tohu o te anga tautoko i ngā tauira kiore, ngā kiko tangata i tangohia mai, me ngā tauira pūtau.

Kātahi ka whakamātauria ngā whakararu e rua. I raro i te aukatinga o te matatini I nā te rotenone, i tiaki tonu te waikano i te matū NAD+ me ngā inenga e pā ana ki te ATP, engari kāore i whakamauru i te kawenga matū whakahāora, i whakahoki i te taurite collagen, i tiaki rānei i te kaha ki te ora. I raro i te whakahekenga whakaputanga AIF, i reira i iti rawa ai te hanga o te pūnaha matatini I, kaua i aukatia mā te rongoā, i whānui te whakaoranga nā te waikano: te taurite NAD, te ahotea whakahāora, te pūmanawa hiko o te kiriuhi, me ngā tohu collagen. He tino tau te akoranga. Ka taea te tautoko i tētahi inenga NAD pai ake ahakoa kua aukatia te matatini I, engari i tēnei tauira whakamātautau i whakawhirinaki te whakaoranga kiko ki tētahi ara matatini I e taea tonu ana te mahi. He mea e hiahiatia ana te huringa ōwehenga i tēnei kōrero, engari kāore i rawaka ko ia anake. Ka whakawhanaketia tēnei take i te rangahau hāora-whakaheke o te uaua here.

Me pēhea te pānui i te whakapae hāora-whakaheke e whai ake nei

Mā ngā tirohanga e toru ka ārai te nuinga o ngā hē whakamāori. Tuatahi, tirohia nō tēhea wāhanga te ōwehenga, ā, nā tēhea takirua tohu ine i whakaputa. Kāore tētahi hua lactate ki te pyruvate o te wai pūtau e whakaatu tika ana i ngā mea kei roto i te kōpū mitokōria. Tuarua, tirohia mēnā e pūrongo ana te pepa i tētahi huringa ōwehenga, i tētahi puna tapeke nui ake, i te whakaoranga ATP rānei, ā, whakaarohia ia mea hei kitenga motuhake. Tuatoru, tirohia ngā mea i mau tonu te hapa: ka kitea i ēnei pepa te ngako kāore i whakatikahia, te hapa matatini I kāore i whakatikahia, te hapa ATP kāore i whakatikahia rānei, i te taha tonu o te tino pai ake o te āhua hāora-whakaheke.

Kāore tētahi wāhanga o tēnei e tū hei aratohu horopeta. Ko ngā rangahau e rima katoa he mahi ki ngā kararehe, ki ngā pūtau, ki ngā tauira kiko rānei, me ngā whakakino kua āta whakahaerehia: ngā kai ewaro wai, te mate huka nā te streptozotocin, ngā hapa matatini I nā te ira, te rotenone, te peroxide, te collagenase. Kāore e taea te huri ngā kukū i ngā ipu whakamātautau hei horopeta mā te waha mā te titiro noa, ā, kāore he tangata i ēnei pepa i tango kahurangi metilīni mō te taurite hāora-whakaheke. He whāiti ake, he whai take ake hoki te kaupapa matua mō te mātauranga rongoā hāora-whakaheke me te horopeta i tētahi kawa whakamahi: ka whakahāoratia e te kahurangi metilīni te NADH, ka huri hoki i te ōwehenga kua inea; i ētahi kiko, ka huri ngā sirtuin i taua huringa hei tangohanga rōpū acetyl me te whakarite anō i te pākia; ā, ko te whai mai o te kiko ka whakawhirinaki ki te pūnaha mahi kāore e taea e te waikano te whakakapi.