glycogen and gluconeogenesis - itkhmerangkor€¦ · gluconeogenesis Ù g6-p manvasna 4; ......

emtabUlIs• 1- esckþIefþIm :famBl nigemtabUlIs : • 2- KøIkUlIs• 3- KøIkUEsnemtabUlIsnigkMNkKúøykUs• 4- vdþsuIRTikGasuIt• 5- kardwknaMeGLicRtugnigpUsVrIlkmµGuksuItkmµ• 5- kardwknaMeGLicRtugnigpUsVrIlkmµGuksuItkmµ• 6- lIBItemtabUlIs• 7- eGtaNulemtabUlIs• 8- GamINUGasuItemtabUlIs• 9- nuyekøGUTItemtabUlIs• 10- karrMlay nigkarRsUbsmasFatuGahar• 11- rsµIsMeyaKHeng Savoeun/2008 1

Heng Savoeun/2008 2

KøIkUEsn

Ù enA~gezøIm‘10g/100gCalika’ nigsac´duM‘1g/100gCalika’Ù bnÞab´BIGt´Gaharry;eBl12-18em¨ag ezøImminmanKøIkUEsneT[teTÙ BBYkstVeRbIR:s´KøIkUEsnCasarZatuRbPBzamBl eRJH;

1- sacduMminGacrMlayCatixøajeGay:nel]n dUcKøúykUseT1- sacduMminGacrMlayCatixøajeGay:nel]n dUcKøúykUseT2- GasuItxøaj´minGacbMEbkenAeRkamlk¡xNÐKµanxül:neT3- stVminGaceRbIGasuItxøaj´CasarZatuedImsMrabsMeyaKKøúykUs:neT

Heng Savoeun/2008 3

segçbGMBIkareRbIKøúykUsemtabUlIsÙ glucose 6-phosphate ‘CacMNucKnøwH’mankMeNItBI KøúykUsesrItamry;

skmµPaBrbs hexokinase rWCaplitplénkarbMEbk glycogen rWgluconeogenesis

Ù G 6-P manvasna 4;- GacRtUv:neRbIsMrabsMeyaK glycogen- GacRtUv:neRbIsMrabsMeyaK glycogen

- GacRtUv:nbMElgtam glycolysis edIm|Ipþl´ ATP nig acetyl-CoA

EdlrgGuksuItkmµeday citric acid cycle

- GacbEgVrcUleTApøÚvmYyeT[t tam pentose phosphate pathway

edIm|Ibeg,It NADPH nig ribose 5-phosphate

- enAkñúgezøIm G6P GacbMElgeTACaKøúykUssMrabnaMecjeTACalikaepSg>tamQam

Heng Savoeun/2008 4

segçbGMBIkareRbIKøúykUsemtabUlIs

Heng Savoeun/2008 5

karrMlayKøIkUEsnÙCabUlIEm D-glucosemansm¬&nÆ α(1-4)nigExñgα(1-6) er[gralsMNl8-14ÙmUelKulKøIkUEsnnimYy>manKøúykUsrhUtdl´ 120 000ÙKøúykUsRtUv:nykmkeRbIR:stamkardkykecjmkCalMdablMeday BInonreducing ends énKøIkUEsn‘xagcugGtman C1-OH group’

Heng Savoeun/2008 6

karrMlayKøIkUEsnmanGg;suImcMnYn3

1- glycogen phosphorylase CMrujpUsVrIlkmµkat´pþacsm¬&nÆ 1,4-glycosid~gKøIkUEsnEdlbeg,It:n glucose 1-P . vabMEbkKøIkUEsnrhUtdl´ExñgEdlmansm¬&nÆ 1,6-glycosid .

Glycogenn + Pi ↔ Glycogenn-1 + Glucose 1-P

2- glycogen debranching enzyme rW amylo 1,6glucosidase CaGgsuIm2- rW CaGgsuImyzaRbePT kat´pþacsm¬&nÆ 1,6-glycosid edIm|IbMEbkExñg

3- phosphoglucomutase bMElg glucose 1-P eGayeTACa glucose 6-P

Glucose 1-P Phosphoglucomutase Glucose 6-P

Ù enA~gezøIm nigkMrgenam buEnþminEmnenA~gsacduMeT glucose 6-P rgedpUsVrIlkmµeTACaKøúykUseRkamGMeBI glucose 6-phosphatase rYcKøúykUsk¾RtUvbeJ©jeTA~gQam

Heng Savoeun/2008 7

Ùphosphorylase P¢abńwgcofactor(pyridoxal-5’-P)

Ù prosthetic group enH‘RsLay vitamin B6’ P©abńwgGgsuImCakUva¨Lg´ tam

clnkarrbs; glycogen phosphorylase

‘RsLay ’ P©abńwgGgsuImCakUva¨Lg´ tamSchiff base(imine) Edl:nbeg,Itrvagbg<M aldehyderbsvaCamYyε-amino group

rbs Lys 680

ÙvaedIrtYCaacid-base catalyst

Heng Savoeun/2008 8

glycogen debranching enzyme

Heng Savoeun/2008 9

phosphoglucomutase

phosphoglucomutase bMElg Glu 1-P eTACa Glu 6-P . bg<MpUsVatRtUv:nepÞrBIactive phospho-enzymeeTAeGay Glu 1-P Edlbeg,It:n Glu 1,6-bisphosphate

(G1,6P). bnÞab´mk G 1,6-Ppþac´pUsVateTAeGayGgsuImvijedIm|IeGaypl G 6-P.

Heng Savoeun/2008 10

karsMeyaKKøIkUEsn

RbtikmµpÞúyKñaénkarsMeyaK nigkarbMEbkKøIkUEsn


CMhanTaMg3énkarsMeyaKKøIkUEsn

k’ phosphoglucomutasebMElg glucose 6-

phosphateeTACa glucose 1-phosphate

x’ UDP-glucose pyrophosphorylase CMrujRbtikmµrvag UTP nig glucose 1-phosphateRbtikmµrvag UTP nig glucose 1-phosphate

EdlkñúgenaH UDP-glucose RtUv:nbeg,ItK’ glycogen synthase CMrujRbtikmµbeg,Itsm¬&nÆÆα(1,4)glycosid

X’ karEbkExñgénKøIkUEsnGacRbRBwtþeTA:neRkamGMeBIén glycogen branching enzymeEdleZVIeGaysm¬&nÆÆ α(1, 6)glycosidRtUv:nbeg,IteLIg


UDP glucose pyrophosphorylase

Ù phosphoryl oxygen én G1P

lukluyeTAelI α-phosphorus atomén UTP edIm|Ibeg,It UDP-glucose nig PPi. glucose nig PPi. Ù PPi rgGuIRdUlIsy¨agel]n edayGg´suIm inorganic pyrophosphatase


glycogen synthase

CMhanbnÞab´énkarsMeyaK glycogen KW glucose én UDP-glucoseRtUv:nepÞreTAeGay C4-OH group eTAelI nonreducing end mYyrbs´glycogen edIm|Ibeg,Itsm¬&nÆ α(1-4)glucosidic;

UDP-glucose + glycogenn → UDP + glycogen n + 1


glycogen branching enzyme


karrkSaKøúykUskñúgQam

ÙtYnaTId*sMxan´rbs´ezøImKWEzrkSakMhab´KøúykUskñúgQameGayenAnwg RbEhl 4 nig6mmol/L (70 – 100 mg/dL)

ÙebIsinCakMhab´rbs´KøúykUssæitenAeRkamkMritenH ezøImRtUvbeJ©jKøúykUseTAkñúgQamÙ dMeNIrkarenHRtUvbJ¢aedayGrmUnglucagonÙ dMeNIrkarenHRtUvbJ¢aedayGrmUnÙedaysar G6P minGacqøgkat´Pñasekasika:n enaHCadMbUgvaRtUvrgGuIRdUlIseday glucose 6 phosphatase

Glucose 6-P + H2O Glucose 6-phosphatase Glucose + Pi

Ù KøúykUsenHcakecjBICalikaezøIm nigRtUv:nQamnaMeTACalikaepSg>. sac´duM nig CalikaxøHeT[tGt´man glucose 6-phosphatseeT dUcenHvaTuk G6P Carbs´vapÞal´


karEktMrUvKøIkUEsnemtabUlIs

1- allosteric control

Ù GgsuIm glycogen phosphorylasenig glycogen synthase zitenAeRkam eday rYmman nigÙ GgsuIm nig zitenAeRkamallosteric controleday effector rYmman ATP, G6PnigAMP


2- hormonal effect on glycogen metabolismÙ emtabUlIs glycogen kñúgezøIm RtUv:nEktMrUveday polypeptide

hormone glucagon

Ù glucagon RtUv:nsMeyaKedaylMEBgkñúgkareqøIytbeTAnwgkMhabrbsKøúykUskñúgQam


KøúykUskñúgQamÙ kñúgsac´duM nigCalikaxøH karEktMrUvRtUv:neRbIeday insulin ehIynwg

hormone epinephrine(adrenalin)nig norepinephrine(noradrenalin)


Ùkarp©ab´rbs epinephrine elI β-adrenergic receptor kñúgekasikaezøIm nigsacduM beg,InkMhab´ intracellular [cAMP] EdlRbtibtþkarbMEbk glycogen

eTACa G6P sMrab´ glycolysiskñúgsacduM rWeTACaKøúykUssMrab´naMecj‘kñúgezøIm’Ù ezøImeqøIytbRsed[gKñaeTAnwg glucagonÙ karcgP©abrbs epinephrine elI β-adrenergic receptor kñúgekasikaezøIm


Ù karcgP©abrbs epinephrine elI β-adrenergic receptor kñúgekasikaezøImnaMeGaybeg,InkMhab´ cytosolic [Ca2+] EdlRbtibtþ ‘promote’ karbMEbkglycogenEdr

ÙeBlKøúykUskñúgQammaneRcIn enaH insulin CMruj‘stimulate’karsMeyaKglycogen kñúgekasikasacduM

ÙezøImeqøIytbpÞal´eTAnwgkMeNInKøúykUsedaybeg,InkarsMeyaK glycogen


glycogen phosphorylase

RtUc)aneFVIeGayskmµedaypUsVrIlkmµRtUc)aneFVIeGayskmµedaypUsVrIlkmµRtUc)aneFVIeGayskmµedaypUsVrIlkmµRtUc)aneFVIeGayskmµedaypUsVrIlkmµ


cAMP-dependent protein kinase


ÙCadMeNIrmYyEdlkñúgenaH lactate, pyruvate, glycerine nigGamINUGasuItRtUv:nbMElgeGayeTACaKøúykUsÙ oxaloacetate CapøÚvecjrbskMNKøúykUs

kMNKøúykUs


bgÐajBIkareRbobeFobrvag

kMNKøúykUs nigKøIkUlIs

Ù Rtg´RbtikmµminRtLb´3rbsKøIkUlIs KWsJ¦aRBYje:¨gcuHeRkam

ÙcMENk kMNKøúykUsmansJ¦aRBYjeLIgelI


pyruvate carboxylase

k’ pyruvate carboxylase CMrujRbtikmµbeg,It oxaloacetate BI pyruvatenig bicarbonate (HCO3

-) edayRtUvkarmYymUelKul ATP


Ù biotinKWCaGñkdwknaMósµ&nkarbUnikedayP¢ab´enAelIuredio grouprbsvaÙ biotin P¢ab´tamlk¡N;sm&¬nÆkUva¨Lg´eTAnwg Lys rbsGgsuIm edIm|I

beg,ItCa biocytin residue

Ù karxVH biotin KWkMr eRJHvamanenAesÞIrRKbcMNIGaharÙ karxVH cMeJHmnusS KWedaysarkarbriePaKsu)teqAeRcIn eRJH

pyruvate carboxylase man prosthetic biotin group

Ù karxVH KWkMr eRJHvamanenAesÞIrRKbcMNIGaharÙ karxVH biotin cMeJHmnusS KWedaysarkarbriePaKsu)teqAeRcIn eRJH

enAkñúgsu)tmanRbUetGuInm¨üageQµaHavidin EdlGacP¢abnigbiotinÙ edaysarmUlehtuenH eZVIeGaykarRsUbyk biotin RtUvraMgsÞHÙ buEnþ su)tEdlRtUv:ncMGin KµanbJØaenH ekIteLIgeT eRJH avidin

RtUvxUcRTg´RTayrbsva nig:ttYnaTI


pyruvate carboxylase man prosthetic biotin group


Rbtikmµ pyruvate carboxylase RbRBwtþeTACa2dMNak;

dMNak´1; ATP eZVIRbtikmµCamYy bicarbonate tamry;karbeg,Itcarboxyphosphate intermediate. CO2 EdlCalTÆpl manzamBlesrIRKb´RKan´edIm|IeZVIkabUsIlkmµ‘carboxylate’biotin.

ÙÙ dUcenH carboxyl group Edl:nP¢ab´nwg biotin RtUv:neZVIeGayskmµ

dMNak2; carboxyl group Edl:neZVIeGayskmµ RtUv:nepÞrBIdMNak2; carboxyl group Edl:neZVIeGayskmµ RtUv:nepÞrBIcarboxybiotin eTAelI pyruvatekñúgRbtikmµ3CMhan edIm|Ibeg,It:n oxaloacetate.

ÙÙ oxaloacetate KWCaZatuepþImsMrab´ gluconeogenesisnig intermediate rbs citric acid cycle


phosphoenolpyruvate carboxykinase

x’ phosphoenolpyruvate carboxykinase CMrujRbtikmµbMElgoxaloacetateeTACa phosphoenolpyruvate

RbtikmµenHRtUvkarmYymUelKulGTP


clnkarénGg;suIm PEP carboxykinase

Õ edkabuksuIlkmµ‘decarboxylation)én oxaloacetate RbRBwtþeTAtamlk¡N; nucleophilic attack enAelIGatUmpUsVrénγ-phosphoryl group rbs´ GTP EdleGayplCaγ-phosphoryl group rbs´ GTP EdleGayplCaphosphoenolpyruvate, GDT nig CO2


Õ kMNKøúykUsnigKøIkUlIseRbIR:sGg´suImCaeRcInrYmKñaÕ EtkMNKøúykUsenARtg´kEnøgRbtikmµ phosphofructokinase nig

hexokinaseRtUv:neZVIeLIgedaysarGg´suImepSg;

kMNKøúykUsnigKøIkUlIs

- fructose 1, 6-bisphosphatase

- glucose 6-phosphatase


fructose 1, 6-bisphosphatase

Õ CMrujRbtikmµbMElg fructose 1, 6-bisphosphateeTA fructose 6-phosphate


glucose 6-phosphatase

Õ CMrujRbtikmµGuIRdUlIs glucose 6-P nigbeg,It:nKøúykUsnig Pi

Gg´suIm glucose 6-phosphatase manenAEtkñúgezøIm


smIkarsrubénkMNKøúykUs

2Pyruvate + 2NADH + 4H+ + 4ATP + 2GTP + 6H2O →

Glucose + 2NAD+

+ 4ADP + 2GDP + 6Pi


kMNKøúykUsTamTareGaymankardwknaMemtabUlItrvagmItUkugRDI nigsuItUsul

karbeg,It oxaloacetateBIpyruvateRbRBwtþeTAEtkñúgmItUkugRDI ÉGg´suImEdlbMElg PEPeTACaKøúykUszitenAkñúgsuItUsul.

oxaloacetateRtUvbMElgoxaloacetateRtUvbMElgeTACa aspartate eday sarGMeBIrbs aspartate

aminotransferase‘pøÚv1’rWeTACamalateedaymalate

dehydrogenase‘pøÚv2’.


karEktMrUvkMNKøúykUs

lMdablMedayénRBwtþkarN¾emtabUlIsEdlmanTMnak´TMngrvagkMhabKúøykUsTabkñúgQam nigkMNkKøykUs kñúgQam nigkMNkKøykUs kñúgezøIm


vdþ cori(cori-cycle)

ADP + GDT + Pi

Glucose Glucose

ADP + Pi

eføIm Qam sac;duM

Gluconeogenesis

ADP + GDT + Pi

ATP + GTP

Lactate

ADP + Pi

Glycolysis

ATP

Lactate


glycogen and gluconeogenesis - itkhmerangkor€¦ · gluconeogenesis Ù g6-p manvasna 4; ......

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