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]