Post on 14-Apr-2017
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¢ab´nwgcofactor(pyridoxal-5’-P)
Ù prosthetic group enH‘RsLay vitamin B6’ P©ab´nwgGgsuImCakUva¨Lg´ tam
clnkarrbs; glycogen phosphorylase
‘RsLay ’ P©ab´nwgGgsuImCakUva¨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
Heng Savoeun/2008 11
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
Heng Savoeun/2008 12
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
Heng Savoeun/2008 13
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
Heng Savoeun/2008 14
glycogen branching enzyme
Heng Savoeun/2008 15
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´
Heng Savoeun/2008 16
karEktMrUvKøIkUEsnemtabUlIs
1- allosteric control
Ù GgsuIm glycogen phosphorylasenig glycogen synthase zitenAeRkam eday rYmman nigÙ GgsuIm nig zitenAeRkamallosteric controleday effector rYmman ATP, G6PnigAMP
Heng Savoeun/2008 17
2- hormonal effect on glycogen metabolismÙ emtabUlIs glycogen kñúgezøIm RtUv:nEktMrUveday polypeptide
hormone glucagon
Ù glucagon RtUv:nsMeyaKedaylMEBgkñúgkareqøIytbeTAnwgkMhabrbsKøúykUskñúgQam
karEktMrUvKøIkUEsnemtabUlIs
KøúykUskñúgQamÙ kñúgsac´duM nigCalikaxøH karEktMrUvRtUv:neRbIeday insulin ehIynwg
hormone epinephrine(adrenalin)nig norepinephrine(noradrenalin)
Heng Savoeun/2008 18
karEktMrUvKøIkUEsnemtabUlIs
Heng Savoeun/2008 19
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
karEktMrUvKøIkUEsnemtabUlIs
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
Heng Savoeun/2008 20
glycogen phosphorylase
RtUc)aneFVIeGayskmµedaypUsVrIlkmµRtUc)aneFVIeGayskmµedaypUsVrIlkmµRtUc)aneFVIeGayskmµedaypUsVrIlkmµRtUc)aneFVIeGayskmµedaypUsVrIlkmµ
Heng Savoeun/2008 21
cAMP-dependent protein kinase
Heng Savoeun/2008 22
Heng Savoeun/2008 23
ÙCadMeNIrmYyEdlkñúgenaH lactate, pyruvate, glycerine nigGamINUGasuItRtUv:nbMElgeGayeTACaKøúykUsÙ oxaloacetate CapøÚvecjrbskMNKøúykUs
kMNKøúykUs
Heng Savoeun/2008 24
bgÐajBIkareRbobeFobrvag
kMNKøúykUs nigKøIkUlIs
Ù Rtg´RbtikmµminRtLb´3rbsKøIkUlIs KWsJ¦aRBYje:¨gcuHeRkam
ÙcMENk kMNKøúykUsmansJ¦aRBYjeLIgelI
Heng Savoeun/2008 25
pyruvate carboxylase
k’ pyruvate carboxylase CMrujRbtikmµbeg,It oxaloacetate BI pyruvatenig bicarbonate (HCO3
-) edayRtUvkarmYymUelKul ATP
Heng Savoeun/2008 26
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
Heng Savoeun/2008 27
pyruvate carboxylase man prosthetic biotin group
Heng Savoeun/2008 28
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
Heng Savoeun/2008 29
Heng Savoeun/2008 30
phosphoenolpyruvate carboxykinase
x’ phosphoenolpyruvate carboxykinase CMrujRbtikmµbMElgoxaloacetateeTACa phosphoenolpyruvate
RbtikmµenHRtUvkarmYymUelKulGTP
Heng Savoeun/2008 31
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
Heng Savoeun/2008 32
Heng Savoeun/2008 33
Õ kMNKøúykUsnigKøIkUlIseRbIR:sGg´suImCaeRcInrYmKñaÕ EtkMNKøúykUsenARtg´kEnøgRbtikmµ phosphofructokinase nig
hexokinaseRtUv:neZVIeLIgedaysarGg´suImepSg;
kMNKøúykUsnigKøIkUlIs
- fructose 1, 6-bisphosphatase
- glucose 6-phosphatase
Heng Savoeun/2008 34
fructose 1, 6-bisphosphatase
Õ CMrujRbtikmµbMElg fructose 1, 6-bisphosphateeTA fructose 6-phosphate
Heng Savoeun/2008 35
glucose 6-phosphatase
Õ CMrujRbtikmµGuIRdUlIs glucose 6-P nigbeg,It:nKøúykUsnig Pi
Gg´suIm glucose 6-phosphatase manenAEtkñúgezøIm
Heng Savoeun/2008 36
smIkarsrubénkMNKøúykUs
2Pyruvate + 2NADH + 4H+ + 4ATP + 2GTP + 6H2O →
Glucose + 2NAD+
+ 4ADP + 2GDP + 6Pi
Heng Savoeun/2008 37
kMNKøúykUsTamTareGaymankardwknaMemtabUlItrvagmItUkugRDI nigsuItUsul
karbeg,It oxaloacetateBIpyruvateRbRBwtþeTAEtkñúgmItUkugRDI ÉGg´suImEdlbMElg PEPeTACaKøúykUszitenAkñúgsuItUsul.
oxaloacetateRtUvbMElgoxaloacetateRtUvbMElgeTACa aspartate eday sarGMeBIrbs aspartate
aminotransferase‘pøÚv1’rWeTACamalateedaymalate
dehydrogenase‘pøÚv2’.
Heng Savoeun/2008 38
karEktMrUvkMNKøúykUs
lMdablMedayénRBwtþkarN¾emtabUlIsEdlmanTMnak´TMngrvagkMhabKúøykUsTabkñúgQam nigkMNkKøykUs kñúgQam nigkMNkKøykUs kñúgezøIm
Heng Savoeun/2008 39
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
Heng Savoeun/2008 40