Th BS o Nh Hien PCN BM Sinh Hoa HYK Pham Ngoc Thach

Mc tiu
1. 2. 3. 4. 5.

M t qu trnh ng phn. M t qu trnh tn to glucose. Hiu chu trnh HMP v ngha ca n . M t qu trnh tng hp v phn ly Glycogen. Nm vng iu ha chuyn ha glucide thng qua cc qu trnh trn,

ThS BS o Nh Hien

y Glucose la trung tam cua

chuyen hoa Glucid y Cac loai ng khac c bien oi thanh glucose tai gan. y Te bao co the d tr Glucose di dang Glycogen va nhanh chong cung cap nang lng khi nhn oi. y Chuyen hoa cua Glucose co the theo 2 hng HIEU KH va YEM KH ( t cung cap nang lng cho nhng mo t hay khong co ty the nh hong cau hay trong tnh trang mo thieu oxy).
ThS BS o Nh Hien

D tr

Oxy hoa- theo ng Pentose-P

GLUCOSE
Oxy hoa-Ly giai glucose

Mot so thuat ng
1. S len men: thoai hoa glucid theo ng yem kh .San pham s len
men co the la

2. ng phan (Glycolysis) : thoai hoa glucose en pyruvat. 3. S thoai hoa glucid trong ieu kien hieu kh : S ho hap (HDP 4. 5. 6.

y Acol ethylic (s len men ru) : vi sinh vat nh nam men. y Acid lactic : s len men lactic

=Hexose Di Phosphate) Glycogen phan (Glycogenolysis) :phan giai glycogen thanh glucose , glucose thoai hoa tiep thanh CO 2 , H2O. Tong hp Glycogen (Glycogenesis) : tong hp glycogen t glucose va cac MS khac. Tan tao glucid (Gluconeogenesis) : tong hp glucose va glycogen t nhng chat khong phai la glucid (pyruvat,lactat, acid amin, glycerol) va nhng chat trung gian co the chuyen hoa trung gian qua pyruvat hay chu trnh acid citric.
ThS BS o Nh Hien 4

Noi dung
1. 2. 3. 4. 5. 6. 7. 1.ng phan (Glycolysis hay HDP) 2.Tan tao Glucose (Gluconeogenesis) 3.Chu trnh HMP (Hexose Mono Phosphate) 4.ieu hoa qua trnh ng phan va tan tao glucose 5.Phan ly glycogen 6.Tong hp Glycogen 7.ieu hoa tong hp va phan ly Glycogen.

ThS BS o Nh Hien

ThS BS o Nh Hien

HDP(Glycolysis-ng phan)
(Chutrnh Hexose diphosphate)
PHA CHUN B Phosphoryl ha Glucose v bin i thnh Glyceraldehyde-3-phosphate

2 Phn ng 1 chiu

ThS BS o Nh Hien

HDP
PHA THU HOCH
Oxy ha v bin i Glyceraldehyde-3phosphate Pyruvate , km vi to ATP v NADH

2 lien ket Phosphate giau nang lng

( )

Phn ng 1 chiu
8

ThS BS o Nh Hien

HDP
C oxygen
Khng oxygen Khng oxygen

ng vt, thc vat va nhieu te bao sinh vat trong ieu kien hieu kh.

Len men Lactat : co c manh , trong hong cau , vai vi sinh vat.

Len men to ethanol vi sinh vt.

9

ThS BS o Nh Hien

HDP

(2)

(2) CHHTB

(2)

(2)

(2)

C oxygen
(2)NAD+

(2)
ThS BS o Nh Hien

(2)

Khng oxygen

(2)Lactate
10

(t bo cht )

Lactate dehydrogenase

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11

HDP

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12

Bin i pyruvate thnh acetylCoA

PDH :Phc hp pyruavate dehydrogenase

ThS BS o Nh Hien 13

Cau truc phc hp enzym Pyruvate dH2 vi 3 tieu phan : E 1 :Pyruvate dehydrogenase E 2 :DihydroLipoyl transacetylase E 3 :DihydroLipoyl dehydrogenase 5 coenzyme (TPP,FAD,CoA-SH, NAD+,Lipoic acid)
ThS BS o Nh Hien 14

C che hoat ong cua phc hp pyruvate dH2: Kh carboxyl oxy hoa

Kh carboxyl oxy hoa (nhan Hydro)

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15

HDP

ThS BS o Nh Hien

16

HDP hiu kh

(2)

(2) CHHTB

(2)

(2)

(2)

C oxygen

To 2 ATP v 2 NADHH+ .
(2)
ThS BS o Nh Hien

(2)
17

K ym kh

K hiu kh

Lactat e

5 5

15

3
=32
ThS BS o Nh Hien 18

To 32ATP
ThS BS o Nh Hien

To 2ATP

19

Hng cu

Hong cau : Tao 2,3 Biphosphoglycerat (thay v 1,3 Biphosphoglycerat ) Jgan vi Hb giup Lai lc vi Oxy J giup hong cau de nha Oxy cho mo.

ThS BS o Nh Hien

20

NGUYEN LIEU CUA HDP

sucrase

Lactase

-amylase

-Bat dung nap Lactose : thieu Lactase trong te bao ruot non J lactose xuong ai trang , vi khuan ruot bien oi thanh chat oc gay gi nc trong long ruot J tieu chay . Uong sa cha Lactase.

HDP
GAN
Fructose 1Phosphate Aldolase

Fructokinase

C ,THAN

Phosphomannose isomerase

Triose kinase 21 ThS BS o Nh Hien

Galactokinase

CHUYEN HOA GALACTOSE

Galactose -1Phosphate

UDP-Glucose Galactose 1Phosphate-Uridylyl transferase

UDP-galactose

UDP-Glucose 4epimerase

UDP-glucose

UDP-Glucose 4ThS BS o Nh Hien epimerase

22

Galactokinase

CHUYEN HOA GALACTOSE

y Thieu 1 trong 3 enzyme :
Galactokinase y UDP-Glucose-Galactose 1-Phosphate-uridylyl transferase y UDP-Glucose -4-epimerase
y

OH

UDP-Glucose Glactose 1-PUridylyl transferase

UDP-Glucose 4-epimerase

UDP-Glucose 4epimerase

Galactosemia : Galactose-mau K va Galactosenieu (+) . 1. Thieu Galactokinase Jtre em b cm mat do tch tu Galactitol thuy tinh the :benh trung bnh neu han che an galactose 2. Thieu transferase : benh nang Jtre em cham phat trien tam than , noi kho , gan b h J chet tre Jche o an khong hieu qua. 3. Thieu epimerase :trieu chng tng t thieu transferase nhng nhe hn neu han che an galactose .
ThS BS o Nh Hien 23

TAN TAO GLUCID

Glucose-6-phosphate

Glucose la nguon nang lng chnh cua: nao ,hong cau , tinh hoan ,tuy thng than, nhau thai. Xay ra chu yeu :gan va vo thng than. Tien chat quan trong : Lactate Pyruvate Glycerol Acid amin tao ng .

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24

CHU TRNH CORI

Tn to glucose

ThS BS o Nh Hien 25

Tan tao Glucid

ng phn

Hexokinase

Glucose Glucose-6-P

Tn to glucose
Glucose-6-Phosphatase

y Xay ra te bao chat. PhosphoFrutosekinase-1 y Ngc chieu ng phan . y 3 phan ng khong thuan nghch : nh nhng enzym khac va con ng khac y Can : y 4ATP y 2GTP y 2NADH Pyruvatkinase
NG PHAN

Frutose -6-P
Frutose-1,6-Biphosphatase

Frutose 1,6-BiP

PEP Carboxykinase 2 PEP

TAN TAO GLUCOSE

2Pyruvate

Pyruvate carboxylase

ThS BS o Nh Hien

(2 )ATP

26

3 phn ng khng thun nghch ca tn to glucose

(1)

(3)

(10)

(Ty th)

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27

ng phn

NGUN GC NADHH+ CN TRONG TN TO GLUCOSE?

ThS BS o Nh Hien

Tn to Glucose
28

Can tao NADH te bao chat cho qua trnh tan tao glucose : te bao chat [NADH] / [NAD+] thap hn trong ty the 105 lan (8x10 4). Phn ng :Pyruvate JPEP (thng qua oxaloacetate trong ty th): 2 cch . 1.T Alanin J Pyruvate (nh transaminase) :NADH cua phan ng thuan nghch Oxaloacetate J Malate cung cap NADH cho phan ng 1,3 BiPhosphoglycerate JGlyceraldehyde-3-P .

PEP carboxykinas e (te bao chat) Malate dehydrogena se (te bao chat)

Ngun gc NADH trong tn to glucose

1
Malate dehydrogena se (ty th) Pyruvate carboxylas e
PEPcarboxykin ase (ty the)

Pyruvate carboxylase

2. T Lactate : bien oi trc

tiep Oxaloacetate J PEP v a tao c NADH phan ng Lactate J Pyruvate.

ALT Alanin
ThS BS o Nh Hien

Lactate dehydrogena se

29

Tien chat cua qua trnh tan tao Glucid

Cac chat trung gian cua chu trnh Acid citric Citrate. -Ketoglutarate. Succinyl CoA. Succinate. Fumarate. Malate.

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30

Tom tat tan tao glucide

y i ngc ng phan t Pyruvate (hay Alanin,Lactate) :7 p thuan nghch -3 phan ng khong thuan nghch. y 3 phan ng khong thuan nghch : y Tao thanh 1 phan t Glucose can :
y 4 ATP y 2 GTP y 2 NADH

Ty th

y Xay ra gan va than cung cap glucose cho nao , c va hong cau . y Pyruvate carboxylase: hoat hoa bi Acetyl CoA Jkhi nguon cua tan tao nhieu (Acid beo) Jvan toc tan tao K. y ong vat khong the x dung trc tiep Acetyl CoA (dan xuat t Acid beo ) e tan tao glucose (thc vat va vi sinh vat co the ) y ng phan va tan tao glucose tuan t c ieu hoa e tranh lang ph khi ca 2 con ng xay ra cung luc.
ThS BS o Nh Hien 31

3 phan ng khong thuan nghch

CHU TRNH HMP (HEXOSE MONOPHOSPHATE)

La qua trnh tao hnh : tao NADPH va Pentose . Xay ra te bao chat.
Nhng te bao can tao mi nhanh nh tuy xng, da, niem mac ruot non :x dung PENTOSE Tao RNA,DNA , 1 so coenzyme nh ATP, NADH,FADH2 va Coenzyme A. Nhng mo khac x dung NADPH trong tong hp nhng chat can thiet : $Ni tong hp Acid beo :gan ,mo m , tuyen vu . $Ni tong hp cholesterol hormon steroid: gan,thng than , sinh duc. Hong cau , giac mac ,thuy tinh the x dung NADPH trong chong cac san pham oxy hoa cua protein,lipid. Hong cau can NADPH chong oxy hoa ,ac biet oi vi ngi thieu enzym G-6-PD bam sinh.
ThS BS o Nh Hien 32

HMP
Pha oxy hoa: khong thuan nghch
Pha khong oxy hoa

Pha oxy hoa

Glucose-6-P Glucose-6-P Dehydrogenase (G-6-P D) 6-Phospho-glucono-lactone Lactonase

Pha oxy hoa

Transketolase Transaldolase
6-Phosphogluconate Dehydrogenase

6-Phospho-gluconate

D-Ribulose-5-Phosphate Phosphogluconate isomerase D-Ribose-5-Phosphate

ThS BS o Nh Hien 33

Thieu Glucose-6-phosphate dehydrogenase

Thieu G-6-P D :benh ly di truyen khoang 400 trieu ngi tren the gii mac phai (25% Chau Phi , 1 phan Trung A va Nam A ni lu hanh sot ret). Benh khong trieu chng . Benh xuat hien sau khi uong nhng loai thuoc hay thc an co tac dung oxy hoa (primaquine, sulfamide) : JLy giai hong cau o at ,tieu Hb. Do thieu G-6-PD gay thieu Glutathion dang kh giup loai cac chat oxy hoa. JPlasmodium falciparum b c che bi tnh trang thieu G-6-PD v no rat nhay cam vi cac tac nhan oxy hoa. ThS BS o Nh Hien

Glucose 6-Phosphate dehydrogenase

G-6-PD

34

Hoat ong cua Transketolase: y Vn chuyn 2 C t 1 Ketose (chat cho) sang 1 aldose (chat nhan). y Coenzym la TPP

HMP Pha khng oxy ha thun nghch: Transketolase.

35

HMP- Pha khong oy hoa:hoat ong cua 2 transketolase

ThS BS o Nh Hien

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HMP-Pha khng oxy ha:Transaldolase

Hoat ong cua Transaldolase: giong aldolase cua chu trnh ng phan (Vn chuyn 1 ln 3 C)

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37

ThS BS o Nh Hien

38

HMP pha khong oxy hoa: thuan nghch

La 1 qua trnh phc tap : ket qua la 6 Pentose phosphate a c bien oi thanh 5 Hexose phosphate .

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39

HMP

Ket hp 2 Glyceraldehyde-3-Phosphate x dung enzym qua trnh tan tao Glucide.

Aldolase

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40

`Glucose-6-P vao qua trnh ng phan hay HMP tuy thuoc :nhu cau cua te bao va nong o [NADP+ ] v [NADPH+ ] te bao chat , iu ha thng qua G-6PD (Glucose-6-phosphate dehydrogenase).

HMP
Glucose
Glucose 6-Phosphate

HDP

`Trong cac qua trnh tong hp :te bao x dng NADPH v nhanh chong chuyen thanh NADP+ , HMP G-6-PD nong o [NADP+ ]K , hoat hoa d lap the enzym G-6-PD , K chu trnh HMP . `Khi qu trnh tng hp chm li : t bo t x dng NADPH (nhu cau ve NADPH cham lai ), nong o [NADPH+ ]K v [NADP+ ]L J NADPH c che G-6-PDJ chu trnh HMP cham lai , G6-P u tien i vao qua trnh ng phan.

NADP+

: c ch : hot ha

`Hoi chng Wernicke-Korsakoff:

ot bien gen transketolase J L ai lc enzym vi TPP (ch con 1/10 so vi bnh thng) Thieu TPP nang (nghien ru kem hap thu cac loai vitamin trong o co Thiamin). J cham HMP , a en hoi chng Wernicke-Korsakoff. ThS BS o Nh Hien41 Trieu chng: giam tr nh tram trong, lan lon , liet khu tru .

IEU HOA NG PHAN VA TAN TAO GLUCIDE

ThS BS o Nh Hien

42

iu ha ng phn v tn to glucose

Hexokinase

ieu hoa ng phan da vao Hexokinase. Phosphofructokinase-1. Pyruvatekinase. ieu hoa tan tao Glucide da vao: Frutose-1,6-Biphosphatase (FBPase -1) : AMP,ATP, Acetyl CoA,Citrate. Pyruvate carboxylase bi Acetyl CoA. Phc hp Pyruvate dehyrogenase bi Acetyl CoA. Frutose-2,6-Biphosphate .

Phospho Frutosekinase-1

Fructose-1,6Biphosphatase (FBPase 1)

Pyruvate kinase

ThS BS o Nh Hien

Pyruvate carboxylas 43

IEU HOA NG PHAN

y Hexokinase :
y 4 loi : Hexokinase I, II, III, IV . y Vai tr khc nhau gia cc Hexokinase gan v c : Hexokinase IV .

y Phosphofructokinase-1 y Pyruvatekinase

ThS BS o Nh Hien

44

Isozyme Hexokinase cua gan va c tac dung khac nhau oi vi Glucose-6-P

Hexokinase co 4 isoenzyme :I ,II , III ,IV . Hexokinase I ,II va III :Km thp . Co nhieu c van . Ai lc manh vi Glucose (Km thap): ban bao hoa nong o Glucose la 0,1 mM phn ng xy ra nhanh chng . Glucose-6-P la chat c che d lap the thuan nghch Hexokinase I,II,III Jtoc o tao G-6-P can bang . Hexokinase IV (Glucokinase) : nhieu gan , phn ng chm v ko di . Km cao : ban bao hoa nong o Glucose la 1 0 mM J khi nong o glucose-mau cao Glucose-mau/oi = 4-5 mM

Hexokinase I (C)

Hexokinase IV (Glucokinase) (Gan)

0,1

> 10mM(sau an) J enzym van hoat ong e gi can bang noi moi Jgiup nong o glucose-mau on nh J ong thi GLUT 2 la chat van chuyen Glucose vao gan hoat ong hieu qua J nhanh chong lam L Glucose-mau . 45
ThS BS o Nh Hien

Co 1 protein c che Hexokinase IV hien dien trong nhan t bo gan . Fructose-6-P ong vai tro chat tac dung d lap the giup protein ieu hoa gan chat enzym J c che enzym . Glucose canh tranh F-6-P J hoat hoa enzym Hexokinase IVJ lam enzym ri khoi protein ieu hoa J di chuyen t nhan ra te bao chat. Mao mch

C tieu thu Glucose /Gan gi Glucose e cung cap cho mau khi oi .

Vai tro Hexokinase VI: trong gan

GAN
T bo cht Nhn

Hot ng

Bt hot

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46

Cac Isozyme Hexokinase phan anh vai tro chuyen hoa glucid khac nhau gia gan va c :vai tro Hexokinase IV
Sau an no Glucose-mau K : GLUT 2 van chuyen Glucose vao gan hoat hoa Hexokinase IV . Nhn oi Glucose L : F-6-P c che HexokinaseIV . Hexokinase IV khong b c che bi G-6-P J Hexokinase IV van tiep tuc hoat ong du cac Hexokinase khac a b c che het.

GAN
T bo cht Nhn

Hot ng

Bt hot

ThS BS o Nh Hien

47

Phosphofructosekinase-1 c ieu hoa bi c che d lap the phc tap

Cht c ch PFK-1 l: ATP v citrate . Cht hot ha PFK-1 l : AMP , ADP v Fructose-2,6-biphosphate. ATP :la c chat va san pham cuoi cua ng phan ,vai tro c che d lap [ATP]KJ c che PFK-1 tai v tr d lap the JL hoat tnh enzym. [ADP] va [AMP]KJ giai c che bi ATP JK hoat tnh enzym. Citrat :chat trung gian chuyen hoa hieu kh pyruvate(san pham au tien cua CT Acid citric), AA va Acid beo . [Citrat]KJ K kha nang c che cua ATP . Citrat la tn hieu noi bao cho thay te bao u nang lng t oxy hoa m va ThS BS o Nh Hien protein.

the

F-2,6-biphosphate:la chat hoat hoa manh cua PFK-1

48

ATP l cht c ch d lp th ca Pyruvate Kinase

Pyruvate kinase t nhat co 3 isozyme (L,M,LM): (Pyruvate kinase L: Liver Pyruvate kinase (c ieu hoa bi s phosphoryl hoa). (Pyruvate kinase M: Muscle Pyruvate kinase . PKA :cAMP- dependent proteine kinase / PP :Proteine Phosphatase

Ch GAN
Glucose-mau L J tiet Glucagon

Tat ca cac mo khac

Pyruvate kinase c vn khng c c ch phosphoryl ha

PKA

Phan ng ngan gan x dung glucose khi glucose-mau L dnh Glucose t do phng thch vo mu PP

ATP Acetyl CoA Acid beo chuoi dai

Dau hieu tha nang lng

c ch d lp 49 th

Glucose-mu L tit glucagon

ThS BS o Nh Hien

Alanin

IEU HOA TAN TAO GLUCIDE

Tai 3 phan ng khong thuan nghch :

Fructose1,6-biphosphatase

(FBPase-1)

Vi s tham gia cua: 1. Acetyl CoA : chat ieu hoa d lap the 2. AMP : chat ieu hoa d lap the 3. Citrat 4. Fructose-2,6-biphosphate 5. Insulin . Ngoai te bao 6. Glucagon.

Trong te bao

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50

Vai tro Acetyl CoA

Acetyl CoA K : ( T oxy hoa acid beo Jdau hieu u nang lng J khong can oxy hoa glucose na . (Khi nhu cau nang lng te bao u J NADH K so vi NAD+ J phosphoryl oxy hoa cham lai Jc che CT Acid citric JAcetyl CoA tch tu. Acetyl CoA cung luc : ( c che d lap the phc hp enzym Pyruvate dehydrogenase Jcham CT Acid citric. ( Hoat hoa d lap the Pyruvate carboxylase J Ktan tao glucide .

Pyruvate

Acetyl CoA K J K tan tao glucide (cch dnh nng lng t Acetyl coA)

ThS BS o Nh Hien

51

Vai tro AMP ,Citrate

1. AMP (dau hieu thieu nang lng): Tuan t c che FBPase-1 va hoat hoa PFK-1 J L tan tao glucide va K oxy hoa glucose e tao nang lng . AMP con kch thch s ly giai glucose . 2. ATP, Acetyl CoA hay Citrate nhieu (dau hieu u nang lng ): c che oxy hoa glucose J nh vay giup tang tan tao glucose . ( ay la nhng phan ng d lap the , ben trong te bao va nhanh chong (vai phan ngan giay). 3. ieu hoa ben ngoai te bao : cham t vai giay en vai phut Insulin va Glucagon : da vao thay oi nong o glucose-mau . Epinephrin :da vao nhng dau hieu cho thay sap can nang lng . Thong qua phosphoryl hoa hay kh phosphoryl 1 protein anh hng en c che d lap the cua enzym tng ng.
ThS BS o Nh Hien

PFK-1

FBPase-1

52

Vai tro AMP ,Citrate

Hot ng d lp th : -ATP:c ch PFK-1 -AcetylCoA: c ch phc hp Pyruvate dehydrogenase. hot ha Pyruvate carboxylase -AMP:gii c ch PFK-1 bi ATP -AMP:c ch FBPase-1 hot ha PFK-1
c ch

Hot ha
Phosphofructokinase-1

c ch

ThS BS o Nh Hien

53

Vai tro Fructose-2,6 -Biphosphate

(Vai tro chnh cua gan la gi nong o glucose-mau luon hang nh. ( Can c che ieu hoa hu hieu : F-2,6-BiP la chat ieu hoa thong qua hormone . (F-2,6-BiP la chat tac dung d lap the cua PFK-1 (ng phan) va FBPase-1 (tan tao glucose). (Glucose-mau L:Glucagon ra lenh cho gan Cung cap va ly giai nhieu glucose cho mau va ngng tieu thu glucose .

(Nguon glucose cua gan t : glycogen va tan tao glucide .

6

2 1
54

ThS BS o Nh Hien

Fructose-2,6-Biphosphate
Hot ng ca PFK-1:
A . Khng c F-2,6-BP: cn 2 mM F-6-P enzym PFK-1 t V max . B. C 0,13 M F-2,6BP : ch cn 0,08 mM F-6-P enzym PFK-1 t V max .

F-2,6-BP hot ha ng phn

B
(0,13 microM)

Kt lun : F-2,6-BP hot ha PFK-1 lm kh nng gn kt vi c cht ca n l F-6-P ng phn .

0,08mM

2mM

ThS BS o Nh Hien

55

Fructose-2,6-Biphosphate
Hot ng ca FBP-1:
A . Khng c F-2,6-BP: ch cn 5 mM F-1,6-BP enzym PBPase-1 t Vmax . B. C 25 M F-2,6-BP : cn n >70 M F-1,6-BP th enzym FBPase-1 mi t V max .

F-2,6-BP c ch tn to glucose
A

B
5microM (25 microM) >70microM

Kt lun : F-2,6-BP c ch FBPase-1 ch vi 1 lng nh F-2,6-BP (1 M) tn to glucose .

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56

Fructose-2,6-biphosphate

(+)
PhosphoFructokinase-1

Fructose Biphosphatase-1

(+)

ng phn

Tn to Glucose

2 qu trnh thun nghch

ThS BS o Nh Hien 57

C che ieu hoa cua Fructose-2,6 -Biphosphate

(F-2,6-BP khong phai la chat chuyen hoa cua ng phan ch la chat ieu hoa Lam Gluocse-mau mc o te bao c tong hp va ly giai bi 2 (Hoat hoa ng phan (c che tan tao Glucide enzym oc lap Khi Gluocse-mau vi QT ng phan. Insulin (Nong o F-2,6-BP trong te bao c Lam Gluocse-mau ieu chnh bang insulin va (c che ng phan glucagon . ( Hoat hoa tan tao Glucide
ThS BS o Nh Hien

PFK-2

FBPase-2

Phospho protein phosphatase

cAMPdependent protein kinase

Glucagon
K(cAMP) Khi Gluocse-mau

58

C che ieu hoa cua Fructose-2,6 -Biphosphate

PFK-1

Hoat hoa ng phan

c che Tan tao Glucose

FBPase-1

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59

Phoi hp ieu hoa gia ng phan va tan tao glucose

NG PHAN 3 enzym cua ng phan la enzym d lap the : hexokinase IV, PFK-1, pyruvate kinase. Hexokinase IV (Glucokinase) trong nhan cua te bao gan va ch ra te bao chat khi glucose te bao chat K. PFK-1 b c che (d lap the ) bi ATP va citrate va c hoat hoa bi AMP v F-2,6-BP (trong gan het cac loai mo va ca te bao gan). Pyruvate kinase b c che (d lap the) bi ATP , va isozym cua gan b c che bi s phosphoryl hoa le thuoc cAMP .

TAN TAO GLUCOSE

Tan tao glucose c ieu hoa nh pyruvate carboxylase (c hoat hoa bi acetyl CoA ) va FBPase-1 (b c che bi Fructose-2,6-Biphosphate va AMP) . Han che chuyen hoa khong hieu qua : 2 con ng (ng phn v tn to glucose) c kiem soat bang tac dung trai ngc cua Frutose-2,6BiPhosphate tren PFK-1 va FBPase-1. Glucagon va epinephrin lam Lnong o F-2,6-BP :bang cach KcAMP va phosphoryl hoa enzym 2 chc nang J bat hoat PFK-2 va hoat hoa FBPase-2 @t o L nong o F-2,6-BP J c ch ng phn /hot ha tn to glucose J K glucose-mu . Insulin lam K nong o F-2,6BP :bang cach hoat hoa 1 phospho protein phosphatase Jgay kh phosphate cua PFK-2 J PFK-2 hoat ong @ K nong o F-2,6BP hot ha ng phn /c ch tn to glucose J L glucose-mu .

CHUYEN HOA GLYCOGEN

1. 1.Ly giai Glycogen(Glycogen phan= Glycogenolysis) 2. 2.Tong hp Glycogen(glycogenesis)

2 qua trnh nay khong thuan nghch :theo 2 con ng khac nhau vi nhng enzym khac nhau

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Phosphorylase : cat lien ket 1-4 glycosid tao Glucose-1-P ( hoat ong chnh) Enzym ct nhnh (debranching enzyme):c 2 hot tnh transferase v (16)glucosidase Chuyen 3 goc Glucose (1,4) sang nhanh khac , cha ra lien ket 1,6 [oligo (16) n (14) glucan transferase ] . Cat lien ket 1,6 tao Glucose t do (hoat ong t)
u t do

Ly giai Glycogen
KET QUA: 9/10 la G-1-P 1/10 la Glucose t do
Hot tnh transferase ca enzym ct nhnh

Glycogen Phosphorylase

Hot tnh (16)glucosidase ca enzym ct nhnh

Glucose-1Phosphate

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Hoat ong cua Phosphorylase

u t do

Pi

Glycogen phosphorylase
u t do

Glucose-1-phosphate
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(Glucose) n1

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Ly giai glycogen :so phan G-1-P

Tai c : do khong co enzym G-6-Phosphatase , nen G-1-P nh Phosphoglucomutase bien oi thanh G-6-P roi x dung ngay tai c (khong vao mau c) . Tai gan : nh Glucose-6-Phosphatase bien oi G-6-P thanh Glucose t do a vao mau (khi nhn oi) o la CHC NANG GLYCOGEN CUA GAN.

C khng c Glucose-6-Phosphatase

Gan

C Gan

ng phan hay oxy hoa (HDP) HMP

Mu

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Hoat ong cua phosphoglucomutase

Glucose-1-phosphate

Glucose-6-phosphate

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Glucose-6-phosphatase hoat ong trong he thong lien vong noi mo cua gan
Glucose-6-Phosphatase hoat ong trong he lien vong noi mo giup ngan cach vi he thong enzym ng phan te bao chat . Thieu Glucose-6-Phosphatase hay G-6-P transporter (T1) di truyen eu a en benh ly :Glycogen storage disease .
T bo cht

GAN

(T1)

(T2)

H thng lin vng ni m (T3)

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Tong quat qua trnh tong hp Glycogen

$Enzym glycogen synthase : gan dan tng Glucose vao glycogen (c chat la UDP-Glucose ) . $Enzym tao nhanh (Branching enzym) :tao nhanh 1,6 glucosid (6 glucose) ,sau khi gan khoang 7 glucose mi ,cat 6 glucose tao nhanh. $Can oan moi : nh Glycogenin (1 protein) va glycosyl transferase tao oan moi t nhat 8 phan t Glucose (1 4).

UDP-Glucose

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Tao thanh UDP-Glucose

Phan ng 1: Hexokinase I , II c va Hexokinase IV gan

1:
Phan ng 2: Phosphoglucomutase

2:
3:

Phan ng 3 : UDP-Glucose pyrophosphorylase

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NDP-sugar (UDP-Glucose (Phan ng 3) pyrophosphorylase Pyrophosphorylase)

Tao thanh UDP-Glucose

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Hoat ong cua Glycogen synthase

Glycogen synthase

au t do cua chuoi Glycogen vi n phan t n>4

au t do mi

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Glycogen dai them vi ThS BS o Nh Hie n n+1 phan t

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Hoat ong cua enzym tao nhanh

1.Con goi la:Amylo(1J4) (1J6)transglycosylase hay Glycosyl (4 J 6)transferase 2. Cach hoat ong: @van chuyen 1 oan glucose (6 hay 7 phan t) t 1 au t do cua glycogen . @sang 1 oan glycogen gan nhat hay tren cung oan (co t nhat 11 phan t). @e gan vao nhom OH cua C 6 Jtao nhanh . 7 phn t Glucose 4 phn t Glucose Glycogen branching enzym iem tao nhanh (1J6) au t do
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iem tao nhanh (1J6)

au t do

(1J4)

au t do

Tng hp Glycogen : cn on mi
Tong hp moi nh Glycogenin (proteine) Moi (primer):t nhat co 8 glucose (1J4) Khoang 12 lan phan nhanh , cha 55 000 pt Glucose , M=107 , k =21 nm. Moi nhanh co t 12 14 phan t glucose
4e 3e
2e

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Tng hp glycogen: hot ng ca on mi

Glucosyl transferase

Keo dai chuoi

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Chuyen hoa Glycogen

Enzym tao nhanh

Tng hp Glycogen
Glycogen synthase

u t do

Phosphorylase Ly gii Glycogen

Glucose 1phosphate

UDP-Glucose Pyrophosphorylase

Enzym cat nhanh

Glucan transferase

Glucose
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Chc nng Glycogen ca gan

T bo GAN

(UDP)

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Glucose-6-P : cht ng ba ng trong chuyn ha glucide

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Phoi hp ieu hoa gia tong hp va ly giai glycogen

Ly giai Glycogen
Isulin PP1 : Phosphorylase phosphatase a Phosphorylase kinase Glucagon, Epinephrin Isulin PP1 : Phosphorylase phosphatase a cAMP Gs :GTP binding protein PKA G-6-P Glucose

Tong hp Glycogen
Glucagon, Epinephrin GSK3:Glycogen synthase kinase 3

y GLYCOGEN PHOSPHORYLASE : ieu hoa d lap the di tac dung cua hormone .

y ieu hoa bi phosphoryl hoa

va kh phosphoryl GLYCOGEN SYNTHASE. 78
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Hot ng ca epinephrine c
Ly gii glycogen Tng hp glycogen

Ly gii glycogen
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Hot ng

Tng hp glycogen

Bt Hot
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:GTP binding protein

Vai tro Glycogen phosphorylase

C
Can co c khan cap

Glucose -mauL

Gan

PKA : cAMP dependent protein kinase

Dong thac enzym

K[Ca 2+]

Phosphorylase a phosphatase PP1

Phosphorylase b kinase

K[AMP]

PP1

Khuych i tn hiu
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Hot ng ca Glycogen phosphorylase

Phosphorylase a phosphatase (PP1)

Phosphorylase b kinase

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gan
C : ATP K gan vao v tr d lap the cua Glycogen phosphorylase bat hoat enzym . GAN : Glycogen phosphorylase ng vai tr 1 b phn cm ng vi glucose. Khi glucose mu Glucose vo gan nng Glusose trong gan cao lm Glucose gn vo trung tm d lp th ca phosphorylase a bin i cu hnh gip Phosphorylase a phosphatase (PP1) d dng kh phosphate ca gc Serinphosphate to Phosphorylase b (km hot ng) ly gii glycogen glucose-mu. Insulin hot ha Phosphorylase a phosphatase (PP1) .

GAN

Insulin

Phosphorylase a phosphatase

PP1
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Phosphorylase Kinase

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(PP 1)
GAN : Insulin hot ha Phosphorylase a phosphatase (PP1) kh P ca Phosphorylase a ( hot ng) Phosphorylase b (km hot ng ) ly gii glycogen glucose-mu.

GAN

Insulin

Phosphorylase a phosphatase

PP1
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iu ha tng hp glycogen nh glycogen synthase

GSK3 :Glycogen synthase Kinase 3

Glycogen synthase c ieu hoa nh gan va kh phosphate INSULIN :hot ha tng hp Glycogen glucose-mu.

CKII: Casein Kinase tao ATP moi e GSK 3 hoat ong

c ch GSK3 : gi cho glycogen synthase hot ha (GSK3 phosphoryl ha 3 gc serin u C tn bt hot glycogen synthase ). Hot ha Phospho PP1: Phospho Proteine Proteine phosphatase Phosphatase(PP1) :Kh 3 phosphat glycogen synthase hot ng .

PP1

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Hot ng ca glycogen synthase kinase 3

IRS-1 :Insulin receptor subtrate 1 PI-3K: Phosphatidylinositol 3-kinase

PIP2: Phosphatidylinositol 4,5biphosphate PIP3: Phosphatidylinositol 3,4,5triphosphate PDK-1: Protein kinase PKB: Protein kinase
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PP1: Phospho Protein Phosphatase

Glucose : gn vo Glycogen phosphorylase kch hot kh phosphate ca glycogen phosphorylase Glycogen phosphorylase b(t do) bt hot ly gii glycogen lm tng hp glycogen. Glucose -6-P : gn vo glycogen synthase bin i cu hnh tr nn d dng c PP1 tip nhn d b kh phosphate glycogen synthase hot ng . Epinephrine ( c) v Glucagon (gan) :hot ha PKA gip phosphoryl ha GM (glycogen Targeting Proteine ) gip PP1 ri khi Glycogen synthase . PP1

ThS BS o Nh Hien

GM:glycogen targeting proteine

Insulin

Epinephrine

Insulin kch hot gn phosphate vo GM (v tr 1) kch hot PP1 kh Phosphate ca 3enzyme Hot ha tng hp Glycogen c ch ly gii Glycogen .

GM

GM GM
KhngH H (KhngH)

Epinephrin :kch hot PKA PKA kch hot gn Phosphate vo v tr 2 ca GM lm PP1 ri khi glycogen PP1 khng tc dng trn Glycogen phosphorylase v glycogen c synthase na.Tc dng ngc insulin. PKA: phosphoryl ha 1 protein (Inhibitor 1) Inhibitor 1 ThS BS o Nh Hie gn Phosphate s gn vi PP1 v c ch nPP1.

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Ch 1 enzym PP1 (Phosphorylase phosphatase 1): c

th kh Phosphate ca 3 enzym Phosphorylase kinase , Glycogen phosphorylase v glycogen synthase

Ly gii glycogen
Epinephrine
PKA

PP1
Isulin

Dng gn Phosphate

Trong t bo PP1 khng dng ha tan m gn kt vi 1proteine gi l GM ( Glycogen targeting proteine ) gip gn vi glycogen v 3 enzym trn . PP1: Dng gn (cht c ch -P) :bt hot nh PKA. Dng hot ha :c ch hot ha d lp th nh G-6-P.

PP1
Isulin

Tng hp glycogen
Isulin Epinephrine Glucagon
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PP1

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ieu hoa chuyen hoa Glucose mu glucid gan

Insulin

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ieu hoa chuyen hoa glucid gan

Glucagon

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Glucose mu

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Glucose-mau K

ieu hoa chuyen hoa glucid gan

K Insulin

Kglucagon

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Glucose-mau L

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Kiem soat tong hp Glycogen c

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Khac biet ga ieu hoa chuyen hoa glucid gan va c

Ly gii glucose gan: dnh cung cp glucose t do cho mu Ly gii glucose c: cung cp cho hot ng co c .

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Tom tat ieu hoa ly giai va tong hp Glycogen

y Glycogen phosphorylase :
y Hoat hoa bi glucagon va epinephrin =
cach KcAMP Jhoat hoa PKA . PKA phosphoryl hoa va hoat hoa phosphorylase b kinase J phosphoryl hoa phosphorylase b khong hoat ong J phosphorylase a h . B c che bi Phosphorylase a phosphatase (PP1) : Glucose gan vao Glycogen phosphorylase a gan Jlam b kh P bi PP1 J bien oi phosphorylase a h J phosphorylase b khong h .

y Insulin:
y Thuc ay a Glucose vao c va y
mo m nh gia tang hoat ong cua GLUT4 tren mang te bao . Hoat hoa tong hp Hexokinase II va IV ,PFK-1,pyruvate kinase , nhieu enzym tong hp lipid .Hoat hoa tong hp glycogen c va gan.

y Gan: Glucagon hoat hoa ly gai

y Glycogen synthase :
y Insulin c che GSK3 la enzym
phosphoryl hoa dang Glycogen synthase a (h) JGlycogen synthase b(khong h ) J KQ: Ktong hp glycogen. Dang b (khong h) tr thanh dang a (h) nh kh phosphoryl bi Phospho preteine Phosphatase (PP 1).

glycogen ,tan tao glucose ,c che ng phan Jtiet kiem glucose cung cap cho nao va cac mo khac. C : epinephrin hoat hoa ly giai glycogen va ly giai glucose Jcung cap ATP cho co c .

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Bnh thng: 70-110mg/dl

Bnh thng : glucose khng c thi ra nc tiu Ngng thn : 180 mg/dl (Nng glucose-mu > 180 mg/dl , glucose s thi ra nc tiu ) ( i tho ng : Khi nng glucose-mu > 126 mg /dl (sau 8-10 gi nhn i)
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Hot ha Gy ra Km hm c ch Tng Gim

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