emtabUlIsemtabUlIs1- esckþIefþIm :famBl nigemtabUlIs : 2- KøIkUlIs3- KøIkUEsnemtabUlIsnigkMNkKúøykUs4- vdþsuIRTikGasuIt4- vdþsuIRTikGasuIt5- kardwknaMeGLicRtugnigpUsVrIlkmµGuksuItkmµ6- lIBItemtabUlIs7- eGtaNulemtabUlIs8- GamINUGasuItemtabUlIs9- nuyekøGUTItemtabUlIs10- karrMlay nigkarRsUbsmasFatuGahar
kEnøgepÞreGLicRtug
karepÞreGLicRtugKW karbeg,It NADH nig FADH2 kñúg glycolysis nig citric acid glycolysis nig citric acid cycle
kMLúgeBldMeNIrdwknaMeGLicRtug
Ù ehtukarN¾ ekItmaneLIgkMLúgeBldMeNIrdwknaMeGLicRtug;1- edaykarepÞreGLicRtugrbsva eTAeGaysarZatuepSg enaH NADH nig
FADH2 RtUvrgerduksuItkmµeTACa NAD+ nig FAD
2- eGLicRtugEdlRtUv:nepÞr cUlrYmkñúgGuksuItkmµ-erdukmµbnþbnÞabénmCÄ mNÐlerdukcMnYn10kñúgkMuebøcGgsuImcMnYn4 munnwgerdukmµGuksuIEsneTACaTwkmNÐlerdukcMnYn10kñúgkMuebøcGgsuImcMnYn4 munnwgerdukmµGuksuIEsneTACaTwk
3- kMLúgeBlepÞreGLicRtug enaHRbUtugRtUv:nbeJ©jBImItUkugRDI Edlplit:nCMralRbUtugkattamPñasmItUkugRDI
ÕzamBlesrIEdl:nrkSaTukkñúg electrochemical grandient
enHbg¡MkarsMeyaK ATP BI ADP nig Pi tamry; oxidativephosphorylation
mItUkugRDIÙ mItUkugRDIman pyruvate dehydrogenaseç GgsuIm citric acid cycleç
GgsuImEdlbMEbkGasuItxøaj´ ehIynwgGgsuIm nig redox protein EdlCab´Tak´Tgkñúg electron transport nig oxidative phosphorylation
Ù mItUkugRDIxusKñaTaMgTMhM nigRTgTay EdlGaRs&yelIRbPBrbsva nigsæanPaBemtabUlIsPaBemtabUlIs
Ù vamanragBgRkeBIEdlmanTMhMRbEhl 0,5 x 1,0 µM
Ù ekasikaGWkarIyUtman2000mItUkugRDIEdlkan´kab´ 1/5énmaDekasikaTaMgmUlÙ vaRtUv:nruMB&TÆedayPñaseRkArelag nigmanPñaskñúgbtCaeRcInpñt´Ù RbUetGuInEdlnaMsRmuHsRmYl electron transport nig oxidative
phosphorylation :ncgP¢ab´kñúgPñaskñúgrbs´mItUkugRDIÙ m¨aRTikKWCasUluysüúg dUccahYyEdlmanGgsuIm cofactornigGuIyug
mItUkugRDI
a- electron micrographénmItUkugRDIstV b- düaRkaménmItUkugRDIstV
düaRkamenH bgðajBIdMeNIrkarepÞreGLicRtug ;exµA ; nigkarbþÚrTItaMgénRbUtug ;Rkhm ;
Ù eGLicRtugRtUv:nepÞrrvag complex I nig complex III eday coenzyme
Q(Q) nigrvag complex III nig complex IV eday peripheral
membrane protein cytochrome c
Ù complex I bUm:nRbUtug4 BIm¨aRTikeTAlMhcnøaHPñasÙ complex III k¾bUm:nRbUtug4 cMENkÉ complex IV bUm:nRbUtug2
lMdab;lMedayénkardwknaMeGLicRtug
Õ Rcvak´dwknaMeGLicRtug CakMebøcRbUetGuInmYyQutmanmCÄmNÐlerdukr EdlmanPaBcUlcitþelIeGLicRtugZMeLIg>‘karekIneLIgénstandard reduction potential)standard reduction potential)
eGLicRtugeZVIdMeNIrkat´tamRcvak´enHBI standard reduction
potential TabeTAx¬s´
segçbkardwknaMeGLicRtugkñúgmItUkugRDI
Ùstandard reduction potentialRtUvbgØajCaBN(ébtg
ÙcMNucEdlbeJ©jzamBl RKb´RKan´sMrab´sMeyaK ATPKWBN(ex[vKWBN(ex[vÙkEnøgskmµPaBrbsGñkraraMg KWBN(RkhmÕ complex I, III nig IV min sMeyaK ATPpÞal´eT Etyk zamBlesrI eTAeZVIeGaymankar bUmRbUtugeTAcenøaHPñasedIm|Ibeg,ItCMralRbUtug
GñkraraMgRcvak;dwknaMeGLicRtug
rotenone ‘ZatuBulrbsruk¡CatiRtUv:neRbIeday Amazonian
Indian edIm|IbMBulRtI ehIyvak¾RtUv:neRbICa insecticideEdr’
pøÚveGLicRtugkñúgPñaskñúgrbs;mItUkugRDI
complex I (NADH-coenzyme Q oxidoreductase)
Ù complex I CMrujRbtikmµdwknaMeGLicRtugBIrBI NADH eTA coenzyme Q
Ù CakMuebøcRbUetGuInd*ZMkñúgPñaskñúgmItUkugRDI Edlman43bUlIbuibTItCamYynwgm¨as´mUelKul 850 kD
Ù vaman flavin mononucleotide mYy‘FMN Ca redox-active prosthetic
group’ nig 6-7 iron-sulfur cluster EdlcUlrYmkñúgkardwknaMeGLicRtuggroup’ nig 6-7 iron-sulfur cluster EdlcUlrYmkñúgkardwknaMeGLicRtugNADH + Coenzyme Q(oxidized form) → NAD+
+ Coenzyme Q (reduced form)
KMrUsMrab;karbUmRbUtug
Ù kñúgRTg´RTayEdlrgGuksuItkmµ RbUtugP¢ab´nwgRcvak´cMeh[gGamINU GasuIténPñasxagm¨aRTicGasuIténPñasxagm¨aRTic
Ù erdukmµ bNþaleGaymankarbþÚrRTg´RTay Edldak´bMEbrRkumEdl:n rgRbUtugkmµ eTAxagsuItUsulénPñas nigbnæytMél pK rbsvaEdl bNþaleGayRbUtugpþac´xøÜnecj
Ù erGuksuItkmµ pþl'eGaymankarbþÚrRTg´RTay EdleZVIeGayRbUetGuIn RtLb´eTArkRTg´RTayedImrbsvavij
Ù kñúg complex I RbUtug4RtUv:nbUmkattamPñaskñúgrbsmItUkugRDIsMrab´eGLicRtugmYyKUr>Edl:npþl´eGayeday NADH
complex II (succinate dehydrogenase complex)
Ù CMrujRbtikmµerdukmµénkUGg'suIm Q eTACa QH2
Ù kardwknaMéneGLicRtugBI succinate eTAkUGg´suIm Q RtUvkarcaM:cnUv FAD Caprosthetic group
Ù eGLicRtugRtUv:nbJ¢Únkattam 4Fe-4S clustrer mYy 2Fe-2S cluster BIr nigcytochrome b560cytochrome b560
Ù zamBlesrIsMrab´karepÞreGLicRtugBI succinateeTA Co Q KWminRKb'RkansMrab´bg¡MeGaymankarsMeyaK ATP eT
Õ kuMebøcenH mansar;sMxan BieRBaHvaGnuJ¦ateGay high-potential electron
cUleTAkñúgRcvak´dwknaeGLicRtug edaykarev[gcomplex IÕÕ KYrktsMKalza complex I nig II mineZVIkarCaesrIeT
karhUréneGLicRtugkat;tam complex II
Ù complex II min:ncUlrYmkñúgkarbeg,ItkMritkMhab´énRbUtugeTÙ buEnþvabMerICaédEdlbeJ©jCaelIkdMbUgnUveGLicRtugcUleTAkñúg
Rcvak´dwknaMeGLicRtug
complex III (ubichinol cytochrome C reductase)
Ù complex III enHCMrujRbtikmµGuksuItkmµénkUGg´suIm Q
Coenzyme Q(reduced form) + Cytochrome C(oxidized) →
Coenzyme Q (oxidized form) + cytochrome C(reduced form)
Ù complex III man b-type cytochrome BIr KW cytochrome c1 mYy nig [2Fe-
2S] cluster mYyÙ complex III GnuJ¦atieGay Co QH2 mYymUelKul yYreGLicRtugBIreTAeZVIerdukmµ cytochrome c BIrmUelKul
complex IV (cytochrome C oxidase)
Ù Complex IV man 4 redox center ; cytochrome a, cytochrome a3 ,
GatUmTg´EdgEdls<al´zaCuB nigGatUmTg´EdgmYyKUrEdls<al´zaCuA centerÙ cytochrome c oxidase CMrujRbtikmµerdukmµeGLIcRtug4sMrab´GuksuIEsn1mUelKul4 cytochrome c(Fe2+) + 4H+ + O2 → 4 cytochrome c
(Fe3+) + 2H2OÙ complex IV cUlrYmbeg,ItCMralkMhabRbUtugkñúgpøÚvBIr;Ù complex IV cUlrYmbeg,ItCMralkMhabRbUtugkñúgpøÚvBIr;1- karbUmRbUtugecjBIm¨aRTiceTAkñúgkEnøgcenøaHPñas2- karbeg,It mUelKulTwkedayeRbIRbUtugkñúgm¨aRTic
erdukmµGuksuIEsnedayerdukmµGuksuIEsnedayerdukmµGuksuIEsnedayerdukmµGuksuIEsneday cytochrome c oxidase
karepÞreGLicRtugcMnYn4mþgmYy>bnþbnÞab´KñaBI CuA eTA cytochrome c 1- nig2- binuclear Fe(III)a3 – Cu(II)B complex RtUv:nrgerdukmµeday karepÞreGLicRtugBIrmþgmYy>bnþKñaBI cytochrome c kattam cytochrome a nig CuA center eTAeGay Fe(II)a3 – Cu(I)B form3- O2 P¢abnwg binuclear complex Edl:nrgerdukmµ edIm|Ibeg,Its¬an Fe(II)3- O2 P¢abnwg binuclear complex Edl:nrgerdukmµ edIm|Ibeg,Its¬an Fe(II)nig Cu(I) atom4- karEbgEckeGLicRtugenAxagkñúg pþleGaymanesærPaBdl peroxy
compound ( Fe(III)-O- - O- -Cu(II)
5- karepÞreGLicRtugmYyeT{t CamYynwgkar:nmkénRbUtug bMElg peroxy
compound eTACa Fe(III)-O- - OH-Cu(I)
6- kar:nmkénRubUtugTI2 nigkartMErtMrg´eGLicRtugeLIgvij pþlCaFe(IV) = O- H2OCu(II)
7- karepÞreGLicRtug mYyeT[tTI4 CamYynwg kartMErtMrgRbUtug eGay pl Fe(III)-OH- -HO-
Cu(II)
8- cugbJ©b´ kar:n mkénRbUtug2bEnæmeT[t eGayplCa 2H2O
CamYynwg Fe(III)a3 -
Cu(II)B complex
Ù RtUv:nesñIeLIgkñúgqñaM1961 edayelak Peter Mitchell Mitchell:nTTYlrgVan´ Nobel PrizekñúgqñaM1978
Ù RTwsþIrbs Mitchell Ezøgza zamBlesrIénkardwknaMeGLicRtug RtUv:nsMéc
pUsVrIlkmµGuksuItkmµ
Ù RTwsþIrbs Mitchell Ezøgza zamBlesrIénkardwknaMeGLicRtug RtUv:nsMéc edaykarbUmRbUtugBI m¨aRTikrbsmItUkugRDI eTAlMhcenøaHPñasedIm|Ibeg,IteLIgnUv electrochemical H+ gradient qøgPñaskñúgrbsmItUkugRDI
zamBlénCMralenHRtUv:nykmkeRbIR:ssMrabkarsMeyaK ATP
coupling of electron transport and ATP synthesis
Ù kardwknaMeGLicRtug‘RBYjébtg’beg,It proton electrochemical gradientkatPñaskñúgrbsmItUkugRDI
Ù RbUtugRtUv:nbUmecjBIm¨aRTic kMLúgeBldwknaMeGLicRtug‘RBYjépÞemX’ Ù karRtLb´cUlmkvijrbsRbUtugeZVIeGayedIrkarsMeyaKATP‘RBYjRkhm’
ATP synthase
Ù ATP synthase ‘EdleKs<al´za proton-pumping ATP synthase nigF1F0-ATPase) KWCa multisubunite transmembrane protein Edlmanm¨asmUelKulsrub 450 kD
Ù elak Efraim Racker:nRsavRCavrkeXIjza ATP-synthase ekIteLIgBIEpñkrg2‘F1 nig Fo’
TMrg´rbs ATP synthase
Ù F1 KWCa water-soluble peripheral membrane protein EdlmanEpñk rgcMnYn5Ù Fo KWCa water-insoluble transmembrane proton channelEdl many¨agehacNasEpñkrgcMnYn8
Ù dicyclohexylcarbodiimide(DCCD) CamUelKulrlaykñúgxøajEdlbg¡aMgkardwknaMRbUtug kattam Fo edayeZVIRbtikmµCamYy Glu residue rbs Fo
subunite
Ù Gg´TIbüÚTik oligomycin B k¾cgP¢ab´nwg Fo subunite Edr edIm|Ibg¡aMgkardwknaMRbUtugEdr
Õ karbg¡aMglMhUrRbUtugBIlMhcenøaHPñas RtLbcUlmkkñúgm¨aRTIkbJÄb´karsMeyaK ATP
uncoupling oxidative phosphorylation
Ù CaeRcInqñaMmkehIy 2,4-dinitophenol(DNP) RtUv:nrkeXIjsMrab´karpþac´‘uncouple’kardwknaMeGLicRtug nigkarsMeyaK ATP
Ù DNP KWCaGasuItexSay rlaykñúgxñaj´ EdlGacqøagkatPñas:nÙ vacgP¢abRbUtugenAEpñkxagGasuIténPñas ehIysayPaykatPñas
rYcbeJ©jRbUtugecaleTAEpñkxag:sénPñasÙ vacgP¢abRbUtugenAEpñkxagGasuIténPñas ehIysayPaykatPñas
rYcbeJ©jRbUtugecaleTAEpñkxag:sénPñas
Õ dUcenH vaedIrtYrCa proton-transporting ionophore
nigrMlayCMral
uncoupler
uncoupling oxidative phosphorylation
Ù kñúgTsSvtSqñaM1920 DNP RtUv:neRbICazñaMGahar‘diet pill’ EdlmanRbsiTÆPaBkñúgkarbJ©úHTMgn. buEnþ Cajy> vabNþaleGaysøab´
karkat;pþac;kñúgCalikaxøaj;BN’etñat begáItkMedAuncoupling in Brown Adipose Tissue generates heat
Ùkarbeg,ItkMedA KWCamuxgarrbsCalikaxøajBN(etñat‘brown fat’ÙCalikaenHmindUcCalikaxøaj´BN(sZmµta‘typical(white) adipose tissue’eTedayehtuzavamanmItUkugRDIy¨ageRcInEdl cytochrome rbsvabNþaleGayekItBN(etñat‘brown color’ekItBN(etñat‘brown color’
Ù kUnstVeTIbekIténBYkznistV KµanerameT dUcCamnusS k¾dUcznistVsmáMesá{mkñúgsisirrdUv TaMgGsman brown fat enAk nigxñgEpñkelIEdlbeg,ItkMedA‘edaykarbeg,ItkMedAEdlsac´duMminkMerIk’
Ù buEnþ GuIRdUlIs ATP EdlekIteLIgkMLúgeBlsac´duMkMerIkk¾beg,ItkMedAEdr
clnkarénkarbegáItkMedAkñúg brown fat
Ù mItUkugRDIén brown fat manrnÆRbUtug‘proton channel’ EdlRtUv:ns<alzauncoupling protein(UCPk¾ehAEdrza thermogenin)
Ù UCP KWCaRbUetGuInEdlKµanvtþmanenAkñúgmItUkugRDIénCalikaepSg>Ù cMeBaHstVEdlZnkñúgtMbnRtCak UCP bg,beg<ItrhUtdl´ 15%énRbUetGuInkñúgÙ cMeBaHstVEdlZnkñúgtMbnRtCak UCP bg,beg<ItrhUtdl´ 15%énRbUetGuInkñúgPñaskñúgénmItUkugRDIrbs brown fat
Ù karhUrénRbUtugkattam UCP RtUv:nbg¡aMg edaykMhabrbs purine
nucleotide(ADP, ATP, GDP, GTP) buEnþkarbg¡aMgenHGacRtUv:nQñHedayGasuItxøaj´esrI
clnkarénkarbegáItkMedAkñúg brown fat
Ù karbeg,ItkMedAkñúgmItUkugRDIén brown fat zitenAeRkamkarRtYtBinitürbsGr&mUnÙ norepinephrine(1: noradrenalin) GnÞgkarplit second messenger cAMP
‘2) nigedayehtuenH cAMP- dependent protein kinase k¾skmµ(3)‘ nigedayehtuenH k¾skmµÙ bnÞab´mk kinase eTAeZVIeGayskmµ hormone-sensitive triacylglycerol lipase(4) edaykareZVIpUsVrIlkmµelIva
Ù lipase EdlRtUv:neZVIeGayskmµ eTAeZVIGuIRdUlIs triacylglycerol (5) edIm|Ipþl´GasuItxøaj´esrI EdleTAraraMgGMeBIbg¡aMgrbs purine nucleotide enAelI UCP (6)
Ù karhUrénRbUtugkatUCPrMsayCMralRbUtugqøgkatPñaskñúgrbsmItUkugRDI
→ karenH GnuJ¦atieGaysarZatuGuksuItkmµ‘substrate oxidation’ bnþeTAeT[t‘nigbeg,ItkMedA’ edayKµankarsMeyaK ATP
karRtYtBinitükarbegáIt ATP
Ù RsþIeBjv&yRtUvkarRbmaN 1500 – 1800 kcal(6300 – 7500 kJ)kñúgmYyézáÙ zamBlenH RsbKñanwgzamBlesrIénGuIRdUlIsRbEhl 200 mol ATP
eTACa ADP nig Pi
Ù mYyvijeT[tcMnYn ATP srubEdlmanvtþmankñúgdgxøÜn kñúgxN;eBlmYy KW <0,1 molmYy KW <0,1 mol
Ù karBit tMrUvkarelI ATP minezreT. vamankarpøasbþÚr100dgkñúgel|}nénkareRbIR:s ATP rvageBledk nigeBlmanskmµPaB
→ skmµPaBéndMeNIrkarplit ATP KWziteRkamkarRtYtBinitüy¨aghµtct edIm|Iza ATP minEdlRtUv:npliteRcInCagkarcaM:ceT
karRtYtBinitükarbegáIt ATP
Ù kalNapleZ[b [NADH]/[NAD+] x¬s´ nigpleZ[b[ADP][Pi]/[ATP] Tab enaHskmµPaB cytochrome c oxidase
KWx¬s´Ù kúñgeBlsMrak el|}nGuIRdUlIs ATP eTACa ADP nig Pi Gb|rimaÙ kúñgeBlsMrak el|}nGuIRdUlIs ATP eTACa ADP nig Pi Gb|rimaehIypleZ[b [ADP][Pi]/[ATP] x¬s´ enaHel|}n oxidative
phosphorylatin KWGb|rima→ ebIskmµPaBRtUv:nekIneLIg pþl´nUvGuIRdUlIs ATP eTACaADP nig Pi dUcenH zycuHpleZ[b [ADP][Pi]/[ATP]