Chinyorwa
Bhuruu yemethylene neNAD+/NADH: kunzwisisa kuenzana kweredox mumasero
Mishumo pamusoro pebhuruu yemethylene neNAD+ inowanzobatanidza zvirevo zvitatu zvakasiyana kuita chimwe chete. Chekutanga ndechekuti reshiyo yeNAD+ kuNADH yakasuduruka ichienda kudivi rakanyanya kuita oxidation. Chechipiri ndechekuti sero rine NAD yakawanda kana yose yaverengwa. Chechitatu ndechekuti kugadzirwa kwesimba kwakadzoreredzwa. Izvi zvinonzwika senyaya imwe chete yekudzoreredza metabolism. Muzviedzo, zvinowanzoparadzana, uye mhedzisiro inonyanya kufadza ndeiya yavanenge vasina kufambirana.
Kuvhiringidzika uku kunonzwisisika nekuti zviyero zvitatu izvi zvinoshandisa mazwi mamwe chete. NAD+ inogamuchira maerekitironi mumaitiro emetabolism yova NADH, yozoti mitochondria yoita oxidation yeNADH kuti idzokere kuNAD+ pacomplex I, ichishandisa simba rinosunungurwa kugadzira ATP. Tsananguro yakazara yenzira iyoyo yemaerekitironi iri mutsananguro yekutakurwa kwemaerekitironi mumitochondria, uye divi resimba riri muATP nemetabolism yesimba. Asi reshiyo nehuwandu hwese zvinhu zvakasiyana. Reshiyo inoratidza kuti mamorekuru anotakura maerekitironi aripo akakamurwa sei pakati peakatakura neasina kutakura. Huwandu hwese hunoratidza kuti mamorekuru aya mangani aripo zvachose. Reshiyo iri nani pasina kuwedzera huwandu hwese inoreva kugovaniswazve, kwete kugadzirwa kwemamorekuru matsva.
Zvikamu zviviri, zviyero zvinoratidza mamiriro zviviri
Pane mumwe musiyano unokonzera kusanzwisiswa kusingawanzoonekwa. NAD iri mucytosol neiri mumitochondria zvakanyanya kupatsanurwa nemembrane yemukati yemitochondria, saka chikamu chimwe nechimwe chinogona kuva chakanyanya kuita oxidation kana reduction choga. Nhamba imwe chete yesero rose inovanza izvi.
Tsvakurudzo yechiropa yakaita kuti kupatsanurwa kwezvikamu uku kukwanise kuyerwa. Kuenzana kwekuchinjana kwelactate nepyruvate kunoratidza reshiyo yeNAD+ kuNADH mucytosol, nekuti lactate dehydrogenase inobatanidza mapeya maviri aya. Kuenzana kwekuchinjana kwe3-hydroxybutyrate neacetoacetate kunoratidza reshiyo yemumitochondria kuburikidza nekubatana kwakafanana. Kana mapeya ese akayerwa munyama yakabatwa nechando pakarepo, sezvakaitwa muchidzidzo chekudyisa makonzo ethanol kwenguva refu, panobuda zviyero zviviri zveredox kubva muchiropa chimwe chete, uye chinhu chemakemikari chinogona kushandura chimwe kupfuura chimwe.
Bhuruu yemethylene inoshanda mugadziriro iyi semutakuri wemaerekitironi pane kuva mafuta anopa simba. Inogamuchira maerekitironi kubva kuNADH pedyo necomplex I, yoita reduction, yozopfuudza maerekitironi acho kune vatakuri vari mberi munzira yacho vakaita secytochrome c. Mhedzisiro yacho ndeye oxidation yeNADH pasina kupfuura nemunzira yose yakajairika. Maitiro aya anotsanangura zvose chinoita kuti ifadze uye muganhu wayo: inogona kuderedza kuzara kunokonzerwa nereduction, asi haigadzirisezve complex yakakuvadzwa kana kugadzira mamorekuru matsva eNAD.
Zvidzidzo zvishanu, maitiro mamwe emhedzisiro yakaparadzana
Tafura iri pasi apa inoronga zvidzidzo zvishanu maererano nenyama yakaongororwa, chiyero cheredox, chiyero chesimba, uye zvakanyatsodzoreredzwa. Verenga makoramu maviri ekupedzisira pamwe chete. Kubatana ikoko ndiko musimboti wechinyorwa ichi.
| Nyama nechakaikuvadza | Chiyero cheredox pakushandiswa kwebhuruu yemethylene | Chiyero chesimba nekutumirana zviratidzo | Mhedzisiro pakushanda |
|---|---|---|---|
| Chiropa chegonzo, kudya ethanol kwenguva refu | Reshiyo dzeNAD+/NADH mucytosol nemumitochondria dzakanyanya kudzoreredzwa; glycerol 3-phosphate yakadzokera pamwero wakajairika | ATP haina kushandurwa neethanol kana kurapwa; ATP yakaderera zvishoma pakushandiswa kwedhayi panguva yekupedzisira yekuyera | Kupinda kwemafuta munyama hakuna kushanduka; lipid netriacylglycerol zvakaramba zvakakwira |
| Masero echiropa nechiropa chembeva dzakadyiswa chikafu chine mafuta akawanda | Reshiyo yeNAD+/NADH nehuwandu hweNAD+ zvakawedzera mumasero nemuchiropa | SIRT1 yakawedzera, PGC-1alpha yakabviswa mapoka eacetyl, DNA yemitochondria nekushandiswa kweokisijeni zvakawedzera, kushandiswa kweAMPK kwaitsamira paSIRT1 | Kuungana kwemafuta muchiropa nesteatohepatitis zvakaderera |
| Mwoyo wegonzo rine chirwere cheshuga | Reshiyo yeNADH/NAD+ yakaderera panguva yeoxidation yezvinhu zvinoshandiswa kuita metabolism mumitochondria yakaparadzaniswa | Kushanda kweSIRT3 kwakawedzera; kuiswa kwemapoka eacetyl palysine kwakaderera panzvimbo 83 pamapuroteni 34 | Mavhoriyamu emwoyo nechikamu cheropa chinobudiswa pakurova zvakavandudzika; kukanganisika kwecomplex I pachayo hakuna kugadziriswa |
| Retina yembeva dzine kushomeka kweAIF nemasero anogamuchira chiedza akaiswa rotenone | Reshiyo yeNADH/NAD+ yakadzokera pamwero wakajairika mumasero; kushushikana kunokonzerwa neoxidation kwakaderera | Kushomeka kweATP hakuna kugadziriswa mumasero; nzira dzekushushikana kwemitochondria dzakadzikama | Ukobvu hweretina nezviratidzo zvemasero anogamuchira chiedza zvakachengetedzwa; kurarama kwemasero kwakavandudzika |
| Runda rweAchilles rwevanhu nemakonzo, kukuvadzwa neoxidant necollagenase | Kuenzana kweNAD+ nemamiriro emakemikari eNAD yose zvakadzoreredzwa zvichiswedera kune zveboka rekuenzanisa | ATP yakawedzera uye ROS yakaderera pakaitika kudzoreredzwa | Zviratidzo zvematrix zvakavandudzika kunze kwepakavharwa complex I zvakananga, apo mamiriro emakemikari akashanduka asi nyama haina kuvandudzika |
Pakasagadziriswa nyama nekugadziriswa kweredox
Chidzidzo chekare kupfuura zvimwe muboka iri chinoramba chiri yambiro yakajeka zvikuru. Makonzo akadyiswa ethanol ichipa 36 percent yesimba akava nereshiyo dzeNAD+/NADH dzakaderera mucytosol nemumitochondria, sezvakayerwa nemapeya ese ari maviri anoratidza mamiriro acho, uye bhuruu yemethylene yaiva muchikafu pamwero ungangoita 42 mg pa kg pazuva yakanyanya kudzivirira shanduko idzodzo. Asi triacylglycerol yechiropa yakanga yave pedyo nekupetwa katatu panguva yekupedzisira yekuyera, dhayi ichivapo kana kuti isipo, uye kuongorora nyama nemaikorosikopu kwakaratidza mafuta akafanana akatenderedza pakati pemalobule echiropa. Vanyori vakataura mhedziso isingafadzi zvakananga: shanduko yeredox inofambirana neoxidation yeethanol haisiyo yoga inogadzira chiropa chine mafuta akawanda. Muverengi anoona reshiyo yakagadziriswa sechiratidzo chenhengo yakagadziriswa anenge ataura zvisizvo nezvechidzidzo ichi. Marongerwo ese echidzidzo, kusanganisira mapoka ekuenzanisa akadyiswa huwandu hwakaenzana uye kutorwa kwemasampuli pakati peusiku pakanga kwakanyanya kudhakwa, anotsanangurwa muchidzidzo cheethanol nechiropa.
Enzanisa izvi netsvakurudzo yechiropa pakudya kune mafuta akawanda, umo shanduko yakafanana yereshiyo yakafambirana nekuvandudzika chaiko kwenyama. Mumasero echiropa uye muchiropa chembeva mushure mekupiwa mushonga nemuromo, bhuruu yemethylene yakawedzera reshiyo yeNAD+/NADH, uye nhevedzano yekutumirana zviratidzo yakatevedzwa nhanho nenhanho: SIRT1 yakawedzera, PGC-1alpha yakabviswa mapoka eacetyl, zviratidzo zvekugadzirwa kwemitochondria nekushandiswa kweokisijeni zvakawedzera, AMPK, CPT-1, nePPARalpha zvikabva zvapinda mukushanda, uye kutanga kushanda kweAMPK kwakaratidzwa kuti kunotsamira paSIRT1. Mbeva dzaidya chikafu chine mafuta akawanda dzakaunganidza mafuta mashoma muchiropa. Tsananguro iri kukurudzirwa ndeyekuti shanduko yeredox pano yakavhura nzira yekudzora majini pane kungoenzanisa mamiriro emakemikari, sezvinotsanangurwa muchidzidzo cheSIRT1 neAMPK muchiropa. Rudzi rwezviyero rwakafanana nerwechidzidzo cheethanol, asi mhedzisiro panyama yakapesana. Musiyano uri munzira dzinotevera, kwete mureshiyo yoga.
Mwoyo neretina: masirtuin, kuiswa kwemapoka eacetyl, nekuchengetedzwa pasina kudzoreredzwa kweATP
Chidzidzo chemwoyo une chirwere cheshuga chinobatanidza shanduko yeredox nekuiswa kwemapoka eacetyl pamapuroteni kuburikidza neimwe sirtuin. Mitochondria ine chirwere cheshuga ine kuiswa kwemapoka eacetyl palysine kwakawandisa pamaenzayimu emetabolism, izvo zvinofambirana nekusakwanisa kuchinjachinja zvinhu zvinoshandiswa kugadzira simba. Bhuruu yemethylene pamwero we10 mg pa kg pazuva yakafambisa oxidation yeNADH nenzira yaitsamira pamwero waishandiswa kubva pa6 kusvika pa18 micromolar mumitochondria yakaparadzaniswa, yakawedzera kushanda kweSIRT3, uye yakaderedza kuiswa kwemapoka eacetyl munzvimbo dzakawanda, uku mavhoriyamu emwoyo nechikamu cheropa chinobudiswa pakurova zvichivandudzika kunyange kukanganisika kwecomplex I kwaivapo kwakaramba kuripo. Chidzidzo ichi chinotaura zvakajeka nezvemaitiro emwero anoshumwa mune dzimwe tsvakurudzo: kuwanda kushoma kunotsigira basa rekutakura maerekitironi richibatanidza reduction, asi kuwanda kukuru kunogona kutsaukisa maerekitironi nenzira isina zvinobatsira, saka mhedzisiro yacho ndeyehormesis pane kungowedzera ichienda kudivi rimwe chete. Kuongororwa kwemapuroteni nezviyero zvemwoyo zvinoshumwa muchidzidzo chekuiswa kwemapoka eacetyl mumwoyo une chirwere cheshuga. Maonero ekushushikana kunokonzerwa neoxidation ari shure kweizvi anotsanangurwa munyaya yekushushikana kunokonzerwa neoxidation nekudzora ROS.
Chidzidzo cheretina chinoendesa kupatsanurwa uku kure zvikuru. Mumbeva dzeHarlequin dzine kushomeka kweAIF, uko kunokanganisa kuunganidzwa kwecomplex I, bhuruu yemethylene yakachengetedza ukobvu hweretina, zvikamu zvekunze zvemasero anogamuchira chiedza, nezviratidzo zvemasero erudzi rwerod, cone, Muller, neganglion. Mumasero anogamuchira chiedza e661W akaiswa rotenone, dhayi yakadzorera reshiyo yeNADH kuNAD+ pamwero wakajairika uye yakaderedza mhando dzeokisijeni dzinokurumidza kuita makemikari pamwero we15 micromolar, asi ATP yakaramba yakaderera pamwero waitsigira kurarama kwemasero. Chimiro nekurarama zvakachengetedzwa pasina kudzoreredzwa kwesimba, pamwe nekudzikamiswa kwemhinduro yemitochondria kumapuroteni asina kupetwa zvakanaka uye kwemitophagy. Mhedzisiro iyoyo inochinja maonero edhayi ichiita kuti ionekwe sechinoderedza kushushikana kunokonzerwa nereduction neoxidation pane kuva chinodzoreredza simba, sezvakanyorwa muchidzidzo chekuchengetedzwa kwemasero anogamuchira chiedza muretina.
Runda: chiyedzo umo mamiriro emakemikari akashanduka asi nyama isina kuvandudzika
Tsvakurudzo yerunda rweAchilles ine maitiro ese ari maviri muchidzidzo chimwe chete uye inofanira kuverengwa zvine hungwaru. Tsananguro yakazara yebazi rimwe nerimwe iri muongororo ye2026 yeAchilles tendinopathy. Runda rwakanga ruchirwara rwakaratidza kupera kweNAD+, reshiyo yakaderera yeNAD+ kuNADH, zviratidzo zvisina kusimba zvecomplex I, ATP yakaderera, uye collagen isina kurongeka. Bhuruu yemethylene yakadzoreredza mamiriro emakemikari eNAD neATP uye yakavandudza zviratidzo zvematrix muzvigadziriro zvekuedza zvemakonzo, zvidimbu zvenyama yevanhu zvakabviswa mumuviri, nemasero.
Zvino kwakauya nzira mbiri dzekuvhiringidza maitiro aya. Pakuvharwa kwecomplex I nerotenone, dhayi yakaramba ichichengetedza mamiriro emakemikari eNAD+ nezviyero zvine chekuita neATP asi yakatadza kuderedza mutoro weoxidant, kudzoreredza kuenzana kwecollagen, kana kuchengetedza kugona kurarama. Pakuderedzwa kweAIF, apo muchina wecomplex I wakanga usina kuvakwa zvakakwana pane kuvharwa nemushonga, dhayi yakadzoreredza zvinhu zvakawanda: kuenzana kweNAD, kushushikana kunokonzerwa neoxidation, voltage iri pakati pemativi emembrane, nezviratidzo zvecollagen. Chidzidzo chinobuda pano chakajeka. Chiyero cheNAD chiri nani chinogona kuchengetedzwa kunyange complex I yakavharwa, asi kudzoreredzwa kwenyama mugadziriro iyi yekuedza kwaitsamira panzira yecomplex I inokwanisa kushanda. Shanduko yereshiyo inodiwa munyaya iyi asi haina kukwana yoga, pfungwa inotsanangurwa zvakare muchidzidzo cheredox mumarunda.
Kuverenga zvirevo zvinotevera zveredox
Kuongorora zvinhu zvitatu kunogadzirisa kusanzwisiswa kwakawanda. Chekutanga, bvunza kuti reshiyo ndeyechikamu chipi uye kuti yakabva papeya ripi rinoratidza mamiriro acho. Mhedzisiro yelactate ku pyruvate mucytosol haitauri chinhu chakananga nezvematrix yemitochondria. Chechipiri, bvunza kana chidzidzo chichishuma shanduko yereshiyo, kuwedzera kwehuwandu hwese, kana kudzoreredzwa kweATP, uye tora chimwe nechimwe sechawanikwa chakasiyana. Chechitatu, bvunza kuti chii chakaramba chakakanganisika: mafuta asina kugadziriswa, kukanganisika kwecomplex I kusina kugadziriswa, kana kushomeka kweATP kusina kugadziriswa zvose zvinoonekwa muzvidzidzo izvi pamwe nekuvandudzika kweredox kwechokwadi.
Hapana chimwe chezviri pano chinotungamirira pakusarudza mwero wekushandisa. Zvidzidzo zvose zvishanu zvakaitwa pamhuka, pamasero, kana pazvigadziriro zvenyama, zvichishandisa zvinokuvadza zvakadzorwa: zvikafu zvemvura zvine ethanol, chirwere cheshuga chinokonzerwa nestreptozotocin, kukanganisika kwecomplex I kunobva pamajini, rotenone, peroxide, collagenase. Kuwanda kwechinhu mumidziyo yekuedzera hakushanduriki kuva mwero wekumedza nekungotarisa, uye hapana munhu muzvidzidzo izvi akanwa bhuruu yemethylene kuti aenzanise redox. Pfungwa inobatanidza mashandiro emishonga paredox nemwero wekushandisa yakaganhurirwa uye inobatsira kupfuura chero hurongwa hwekushandisa: bhuruu yemethylene inoita oxidation yeNADH ichishandura reshiyo inoyerwa, masirtuin anoshandura shanduko iyoyo kuita kubviswa kwemapoka eacetyl nekurongwazve kwemetabolism mune dzimwe nyama, uye kuti nyama inotevera here zvinotsamira pamichina isingagoni kutsiviwa nedhayi.