Glycolysis and Gluconeogenesis

Glycolysis and Gluconeogenesis

CHUYN HA GLUCID Bs. Chi Mai Mc tiu Trnh by c con ng ng phn trong iu kin i kh v ym kh. Trnh by c qu trnh tn to glucose Trnh by c chu trnh pentose Trnh by c qu trnh thoi ha v tng hp glycogen.

Mc lc 1. S thoi ha glucose 1.1.Con ng ng phn 1.2.S thoi ha tip theo ca pyruvat 1.3.Con ng pentose phosphat 1.4. Chuyn ha ca cc monosaccarid khc 2. Tn to glucose 3. Chuyn ha glycogen 4. iu ha chuyn ha glucid 5. Ri lon chuyn ha glucid

D tr Oxy ha bi con ng pentose phosphat Oxy ha bi con ng ng phn ng phn (Glycolysis) (Con ng hexose diphosphat)

Mt phn t glucose thoi ha thnh 2 phn t c ba carbon l pyruvat v nng lng to thnh di dng ATP v NADH. y l con ng chuyn ha u tin c bit n v c hiu r nht Xy ra bo tng, qua 2 giai on gm 10 phn ng. Giai on hot ha: 5 phn ng. Giai on oxy ha sinh nng lng: 5 phn ng. Phn ng tng qut ca ng phn

(glycolysis) Glucose + 2 NAD+ + 2 ADP + 2 Pi 2 pyruvat + 2 NADH + 2H+ + 2 ATP + 2 H2O G = -85kJ/mol S PHN CA PYRUVAT iu g xy ra vi 2 phn t pyruvat? C 2 cch thc ty theo iu kin mi trng. iu kin

thiu oxy hoc k kh iu kin k kh iu kin i kh Xy ra khi co c mnh,

hng cu, mt s vi khun Ln mn ru nm Chu trnh acid citric

ng vt, thc vt, nhiu loi vi khun trong iu kin i kh S phn ca pyruvat m ng vt trong iu kin ym kh Ln men ru nm

S phn pyruvat trong iu kin i kh S phn pyruvat trong iu kin i kh Trong iu kin i kh Pyruvat i vo ty th, b kh carboxyl oxy ha thnh acetyl CoA. Acetyl CoA i vo chu trnh acid citric b oxy ha thnh CO2 v H2O.

Bilan nng lng: Glucose 2 pyruvat: 2 ATP 2 NADH ( phn ng 6): 6 ATP hoc 4 ATP 2 Pyruvat 2 Acetyl CoA: 6 ATP 2 Acetyl CoA: 24 ATP Cng: 38 ATP (hoc 36 ATP)

Con thoi malat- aspartat Con thoi glycerol 3- phosphat Dn xut ca vitamin B1. Thiu B1 gy beriberi ( dch, sng au ). Quan trng trong ph v lin kt gn nhm carbonyl, nh acid -cetonic. Tng hp v thoi ha 2,3 DPG trong hng cu

Glyceraldehyd -3- phosphat GAPDH 1,3- diphosphoglycerat PGK 3-phosphoglycerat PGM 2-phosphoglycerat

Mutase Pi Phosphatase 2,3diphosho glycerat Bo ha oxy (%) ng cong bo ha oxy hng cu ngi bnh thng,

bnh nhn thiu ht Hexokinase v pyruvat kinase Thiu ht Hexokinase Ngi bnh thng Thiu ht pyruvat kinase pO2

ngha ca con ng ng phn Cung cp nng lng cho cc hot ng sng ca t bo Cc sn phm trung gian l tin cht sinh tng hp cc cht cho c th CHU TRNH PENTOSE PHOSPHAT (con ng hexose monophosphat) y l mt cch thoi ha khc ca glucose 6phosphat. Xy ra bo tng ca t bo, glucose c

phosphoryl ha 1 ln ri b oxy ha. Quan trng cc t bo phn chia nhanh nh ty xng v da, nim mc rut (tng hp RNA v DNA). Cng quan trng cho cc t bo cn NADPH bo v chng li tc nhn oxy ha (hng cu, vng mc) v cho qu trnh sinh tng hp acid bo (m m, gan), cholesterol (gan, tuyn sinh dc, v thng thn). Giai on 2:

s bin i ca cc pentose Giai on 1: oxy ha Chu trnh Pentose Phosphat cc t bo nhu cu ch yu l NADPH, cc phn t ng 5C s i tip vo giai on th 2

6 phn t ng 5 carbon phosphat trao i vi nhau cc mu 2 v 3 C ti to li thnh 5 phn t glucose 6-phosphat. S phn ca G6-P ph thuc vo nhu cu ca t bo v vo nng tng i ca NADP+ so vi NADPH Cc glucid khc i vo

con ng ng phn Nhiu ng khc cng i vo con ng ng phn sau khi chuyn thnh cc sn phm trung gian ca con ng ny. Sucrose Gm D-glucose v D-fructose fructose c th b phosphoryl ha bi hexokinase sinh ra fructose 6-phosphat, v c th i vo ng phn.

Mg 2 Fructose ATP fructose 6 - phosphate ADP Thoi ha Fructose gan c phosphoryl bi fructokinase C-1 Mg 2 Fructose ATP fructose 1 - phosphate ADP

Thoi ha Fructose gan (tip) Thoi ha Fructose gan (tip) Triose phosphate isomerase chuyn dihydroxyacetone phosphat thnh GAP Glyceraldehyd c phosphoryl bi triose kinase Mg 2

glyceraldehyde ATP glyceraldehyde 3 - phosphate ADP THOI HA GALACTOSE TN TO GLUCOSE (Gluconeogenesis) S to thnh glucose t cc sn phm chuyn ha ca glucid, lipid, protein; khng phi t cc monosaccharid khc. L qu trnh i ngc li con ng ng phn, tr 3 phn ng khng thun nghch i

hi cc phn ng khc thay th. ng phn Tn to glucose ng phn Tn to glucose im khi u cho qu trnh tn to

glucose quyt nh pyruvat chuyn thnh PEP nh th no. Tn to glucose (Gluconeogenesis) Tn km cho t bo, cho c th. to 1 phn t glucose tiu tn mt 4ATP v 2GTP v oxy ha 2NADH thnh NAD+. Tn to glucose (Gluconeogenesis) L cn thit v mt s m s dng ch yu glucose do mu cung cp, v d no v h

thn kinh trung ng. Tn to glucose xy ra ch yu gan, mt phn rt nh v thn (10%). Chu trnh Cori Gan Glucose Mu Glucose

Lactat Lactat C Glucose,Glycogen Lactat Chu trnh Glucose- Alanin ng phn v tn to ng

C th khng th ng thi va xy ra hai qu trnh trn ng thi vi tc cao. Kt qu s l tiu tn nhiu ATP v sinh ra qu nhiu nhit!! Hai qu trnh trn c iu ha tng h v phi hp sao cho mt qu trnh tng ln th qu trnh kia gim i v ngc li. CHUYN HA GLYCOGEN PPi

Pyrophosphatase 2 Pi UDP- Glucose UTP Glucose- 6- P UDP-Glucose Pyrophosphorylase

Glycogen Synthase UDP Glycogen (Glucose)n+1 Glucose- 1- P Phosphoglucomutase

Glycogen (Glucose)n Glycogen Phosphorylase Glycogen (Glucose)n Pi

Thoi ha glycogen Cu trc ca glycogen -(1>4) Linkages -(1>6) Linkage -(1>4) Linkages Thoi ha glycogen Glycogen phosphorylase

Enzym ct nhnh (glycogen debranching enzym) Limit Branch (4 residues) -(1>4) t ransglycosylase (group t ransf er react ion) -(1>6) glucosidase Glucose

Phosphoglucose mutase Glucose1P Glucose6P Kt qu: Thoi ha glycogen khong 90% sn phm l Glucose-1- phosphat, 10% l glucose t do Tng hp glycogen Xy ra tt c cc m, nhng ch yu

gan v c Xy ra bo tng ca t bo Nguyn liu l glucose Tng hp mch thng v mch nhnh UDP-Glucose Pyrophosphorylase O HN O

O O P O O

P O O O O

P O O CH 2 N O

UTP H H H

OH OH H O UDP-Glucose Pyrophosphorylase

CH 2OH H HO O H OH H H

H CH2 OH H O O OH Glucose- 1- P

P O HO O

PPi H H OH H I norganic Pyrophosphat ase 2 Pi

HN O O H O OH

P O O O O P

O O CH 2 N O

UDP- Glucose H H H OH

OH H Glycogen Synthase O UDP- Glucose CH2 OH H HO

HN O H OH H H O

O O P O P O CH2 O O H OH H H OH UDP

HO CH2OH HO O OH Oxonium I on

O N O H H OH

Glycogen Synthase CH2 OH CH2 OH HO HO CH 2 OH O

H H O OH H H

OH O OH OH H

H OH H H OH O

Glycogen: (Glucose)n CH2 OH O OH H CH 2OH

O H O Oxonium I on H

O H H O H O

CH2 OH OH H H OH H

O H O OH H H

OH H Glycogen: (Glucose)n+1 H O Tng hp mch nhnh

Glycogen Branching Enzym ~7 Glucosyl Residues Amylo-(1,4>1,6)-Transglycosylase 4 Residues f rom (Branching Enzyme) exist ing branch iu ha chuyn ha glucid iu ha hot tnh enzym: - Thay i tc sinh tng hp & thoi ha - iu ha d lp th hoc ha hc

- Tch cc enzym khi c cht nh nhng khoang di t bo iu ha nhanh (tnh bng giy hoc nhanh hn) mc trong t bo thng l d lp th Tc ng ca cc hormon thng chm hn (giy n gi) thng l s thay i ha hc hoc thay i tng hp enzym iu ha tng h ng phn & tn to ng Ba enzym ca con ng ng phn c iu ha d

lp th: Hexokinase, PFK-1, Pyruvat kinase - HK c gi trong nhn t bo gan, gii phng khi glucose bo tng tng - PFK-1 : c ch d lp th bi ATP, citrat. Hoat ha bi fructose 2,6-diphosphat. - Pyruvat kinase: c ch d lp th bi ATP Tn to ng: c iu ha pyruvat carboxylase (acetyl-CoA hot ha) v Fructose1,6-diphosphatase (F2,6 diphosphat v AMP c ch) Hai qu trnh c iu ha tng h d lp th ch yu tc dng i lp ca F 2,6-diphosphat trn PFK-1 v

Fructose1,6-diphosphatase Glucagon v epinephrine lm gim [Fructose 2,6diphosphat]. Insulin lm tng [Fructose2,6-diphosphat]. iu ha tng h tng hp & thoi ha glycogen Glucagon hoc epinephrin lm tng [AMPv], hot ha Protein Kinase, lm phosphoryl ha v hot ha phosphorylase kinase. Phosphorylase kinase phosphoryl ha Glycogen phosphorylase dng b thnh dng a- dng hot ng. Phosphoprotein phosphatase 1 (PP1)kh P ca

dng a chuyn sang dng b= km hot ng Glycogen synthase a b bt hot khi c phosphoryl ha bi GSK3. Insulin ngn cn tc dng GSK3. PP1, c hot ha bi insulin, kh phosphat ca glycogen synthase b. iu ha ha hc ATP Phosphorylase b (Less Act ive)

Dimer ADP Phosphor ylase Kinase Phosphor ylase(P) a (More Act ive)

Phosphopr ot ein Phosphat ase-1 Pi P P P P

H2O T et ramer ATP ADP Phosphorylase Kinase

Glycogen S ynthase a (High Activity) Glycogen Synthase(P) b Phosphoprotein (Low Activity) Phosphatase-1 Pi H2 O

iu ha d lp th Enzyme Negative Phosphorylase a (more active) Glucose

Phosphorylase b (less active) ATP G6P Gycogen Synthase a (high activity) Glycogen Synthase b (low activity) ADP Pi Positive AMP G6P iu ha d lp th

ATP Phosphorylase ADP Phosphorylase b (Less Act ive) T Form ATP and/ or G6P AMP

Phosphorylase b (More Act ive) R Form Kinase Phosphorylase(P) a (More Act ive) T Form Pi Phosphoprotein H2O Phosphatase-1

Glucose Phosphorylase(P) a (Most Act ive) R Form Ri lon chuyn ha glucid 1. 2. 3.

4. 5. 6. H ng huyt (Hypoglycemia) Thiu viatmin B1 i tho ng Bnh glycogen bm sinh Bnh galactose mu bm sinh Bnh khng dung np fructose bm sinh

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