Chng II

BAI GIANG SINH HOA HOC

Phan II TRAO OI CHAT

S BIEN DNG GLUCID

1. Vai tro cua bien dng glucid 2. S tieu hoa va hap thu 3. Bien dng glycogen 4. S ng phan 5. Chu trnh Krebs 6. Chu trnh pentose phosphate 7. S tan sinh ng

VA NANG LNG SINH HOC

Chng II- BIEN DNG GLUCID

TP.HCM - 2007

8. ieu hoa bien dng glucid

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1. VAI TRO CUA S BIEN DNG GLUCID Nguon goc : - Ngoai sinh : thc an tinh bot, ng oi, cellulose. - Noi sinh : thoai bien glycogen d tr , tan sinh ng t amino acid, glycerol, lactate. Vai tro : - Cung cap 70 80% nhu cau nang lng, - Cau tao mo bao (glycoprotein) - Kh oc (acid glucuronic)
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2.TIEU HOA
TIEU HOA TINH BOT (thu da day n mot tui) TIEU HOA CELLULOSE (thu da day kep bon tui)

TIEU HOA TINH BOT - Chu yeu xay ra ruot non. - Cac enzyme va tac ong : (1) -amylase (nc bot, dch ruot, dch tuy) ( 1 4 glucan hydrolase) thuy phan tat ca cac lien ket glycosidic (14) cua amylose va AP TINH BOT oligosaccharide + maltose + glucose va dextrin (cha LK 1 6) (2) 1 6 glucosidase (dch ruot) : cat lien ket 1 6 (3) Maltase : thuy phan maltose 2 glucose (4) -amylase (thc vat): p/giai tinh bot maltose
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TIEU HOA CELLULOSE Cellulose la thc an glucid quan trong cua thu nhai l i da day kep (4 tui): da co, da to ong, da day trc da la sach va da mui khe (da day tuyen) S tieu hoa xay ra chu yeu da co nh he vi sinh vat ky sinh o (protozoa, nam va vi khuan). Ket qua trong mot ngay em tao ra khoang 4 kg cac acid beo bay hi, trong o : - Acid acetic : 75% - Acid propionic : 15% - Acid butyric : 10%

Vi sinh vat da co phan huy cellulose va chat bot ng ngoai te bao vi sinh vat oligosaccharide SF chuoi C ngan c a vao te bao vi sinh vat thuy phan hoac phosphoryl phan thanh cac phan t ng n (glucose). Glucose c len men tao ra pyruvate bien oi thanh
Hnh 4.1. H TH NG TIU HA TH NHAI L I 1. Receptor khoang mieng 2. ng dan t receptor khoang mieng 3. Trung khu than kinh hanh tuy 4. Si ly tam i vao than kinh me tau 5. Thc quan 6. Da co 7. Ranh thc quan 8. Da to ong 9. Da la sach 10. Da mui khe 11. Vo nao
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acid beo bay hi (acetate, propionate, butyrate), CO2, CH4 (hnh 2.1)

(1)

(3)

(2)

3 CON NG CHUY N HA CHNH C A GLUCOSE

Hnh 2.1 : S o phan giai glucid trong da co
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3. S BIEN DNG GLYCOGEN 3.1. S THOAI BIEN GLYCOGEN (Glycogenphosphorolysis) Cac enzyme : - Phosphorylase : cat lan lt cac lien ket (1 4)- glycosidic au khong kh G-1-P. - Glucantransferase : chuyen 3 goc glucose sang mach ben -> lam boc lo lien ket (1 6). - Amylose (16) glucosidase : cat lien ket (1 6) lam mat nhanh cua amylopectin. - Phosphorylase tiep tuc cat cac goc G cua amylose G-1-P G-6-P G vao mau, hoac oh NL
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Cau truc phan t glycogen

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Hnh 2.2 : S o thoai bien glycogen

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Glycogen

(C6H10O5)n Phosphorylase Pi

(C6H10O5)n-1 + n(Glu-1-P) (n-1)Pi

- Glucantransferase - Amylose (16) glucosidase

Glu-1-P gan : Glu-6-P

P.glucomutase Phosphatase

Glu-6-P Glucose (tang ng huyet)

- Pi

c : Glu-6-P tham gia qua trnh ng phan e giai 15 phong nang lng.

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3.2. TONG HP GLYCOGEN GAN VA C (Glycogenesis)

Hexokinase (1) Glucose + ATP Glucose-6-P + ADP P.glucomutase Glucose 1- P Glucose- 6-P (2) Glucose 1-P + UTP UDP-glucose + H4P2O7 H4P2O7 + H2O 2 H3PO4 Glycogen(3) UDP-Glu + Glycogen primer synthetase (C6H10O5)n +1 + UDP
(m ch amylose)

(1) Hoat hoa glucose CH2OH OH

G-6-P

Glu -1-P
6CH O2 P

Hexokinase OH OH
ATP.Mg2+ ADP.Mg2+

OH

OH OH Glucose 6-P CH2O-

OH

UDP + ATP UTP + ADP (4) T/l p chu i amylopectin amylose (1,4 1,6) transglucosidase Mot he thong hoan chnh cho s tong hp glycogen trong c the oi hoi: G-1-P + UTP + glycogen primer + glycogen synthetase va 17 amylo(1,4 1,6) transglucosidase

OH Glucose Glucose 6-P

P.glucomutase

OH

O- P OH Glucose 1-P

OH

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CH2O- (2) Thanh lap chat trung gian UDP-Glu O- P OH Glucose 1-P CH2OOH OH + Uridine triphosphate (UTP) - 2Pi
HN 3
2

(3)TL mach amylose (1 4):goc Glu tach khoi UDP-Glu va gan vao au khong kh cua mot oan glycogen moi (primer) vi s thanh lap lien ket glycodidic (1 4) :
O
4 5 1 6

OH

UDP

Glycogen synthetase UDP-Glu + (C6H10O5)nprimer (C6H10O5)n+1

CH2OH
4 OH 5 1

CH2OH O
4 OH 5 1

CH2OH O
5 4 OH 1

OH

O O 5 O-P O- P -O-CH2 OH OH OH 4 H
3
2

HO H
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O-R(n+1)

Uridine diphosphoglucose (UDP-Glu)

OH

OH

OH
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OH

M ch amylose v i lien k t glycodidic (1 4)

OH

(4) Tao nhanh : E amylo(1,4 1,6)transglucosidase chuyen 1 phan chuoi 14 (toi thieu 6 goc Glu) sang chuoi ben, tao iem phan nhanh vi LK(16)

Amylopectin

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4. S NG PHAN (Glycolysis) (S o Embden-Mayehoff EM) 4.1. MUC CH : oxy hoa glucose e lay nang lng trong ieu kien k kh (ngheo hoac vang O2) - Xay ra trong mo bao ngheo O2 s ng phan. - Xay ra VSV s len men - ATP c thanh lap khong i qua chuoi ho hap ma do s phosphoryl hoa trc tiep c chat. - Hieu qua khai thac nang lng t glucose ch khoang 2-3%
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4.2. NAM GIAI OAN NG PHAN : GI : Hoat hoa glucose G-6-P (p1 ton 1 ATP) GII : Bien oi G-6-P (C6) 2 SF C3 co kha nang b oxy hoa (p 2-3-4-5, ton 1 ATP) GIII : O.h 2Glyceraldehyde-3-P 2 Glycerate-3-P (p 6-7, TL 2ATP + 2 NADH + H+) GIV : B/oi 2 Glycerate-3-P 2 Pyruvate (p 8-9-10, TL 2 ATP) G V : Kh 2 Pyruvate 2 Lactae (p 11)
Hnh 2.5 : S o qua trnh ng phan Embden-Mayehoff (EM)
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(s dung 2 NADH+H+ t GIII

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CAC PHAN NG NG PHAN EM GI : Hoat hoa glucose G-6-P ( ton 1 ATP) (1)Hoat hoa glucose -> G-6-P vi enzyme xuc tac hexokinase. P nay khong thuan nghch CH2OH Hexokinase OH OH OH OH Glucose
ATP.Mg2+ ADP.Mg

GII : Bien oi G-6-P (C6) -> 2 SF C3 co kha nang b oxy hoa (p 2-3-4-5 , ton 1 ATP) (2) ong phan hoa G-6-P Fructose-6-P. Enzyme phosphoglucose isomerase
OH

CH2O-P=O OH

CH2O- P OH OH OH Glucose 6-P

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OH

OH 2+

OH OH

OH

P -O-CH2 Phosphoglucose 5 isomerase H 4 OH

CH2OH OH OH
3 2

Glucose 6-P

Fructose 6-P
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(3)Phosphoryl hoa lan 2 Fru-1,6-diP Enzyme xt phosphofructokinase, tieu ton ATP lan th 2. Phan ng khong thuan nghch, quyet nh toc o ng phan. P -O-CH2 H OH
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CH2OH

P -O-CH2

CH2O- P OH OH

OH OH H P.fructokinase
ATP.Mg2+ ADP.Mg2+

OH

Fructose 6-P

Fructose 1,6- di P
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(4) Phan cat phan t C6 thanh 2 phan t C3 vi s xuc tac cua aldolase CH2- O- P C=O CH2OH CH2-O- P Dihydroxyacetone C=O Aldolase phosphate HO-C- H O H- C- OH C H H- C- OH CH2O- P CH - OH CH2- O- P Fructose 1,6- di P Glyceraldehyde 32 3 phosphate

(5) 2 triose chuyen hoa lan nhau , chu yeu tao thanh glyceraldehyde-3-P la san pham c oxy hoa. Enzyme xt la triosephosphate isomerase Nh vay sau 5 p : 1p/t Glu s dung 2 ATP 2 pt glyceraldehyde-3-P O Triophosphate C H CH2- O- P isomerase CH - OH C=O CH2- O- P CH2OH Glyceraldehyde Dihydroxyacetone 3 phosphate (aldose) phosphate (ketose) 33 (5%) (95%)

GIII : O.h 2Glyceraldehyde-3-P 2 Glycerate-3-P (p 6-7, TL 2ATP + 2 NADH + H+) (6) oxy hoa glyceraldehyde-3-P nh enzyme glyceraldehyde 3-phosptate dehydrogenase (tetramer) hnh thanh noi (~ P) trong SP 1,3 BPG va NADH+ H+ O C H + NAD CH - OH +Pi CH2- O- P Glyceraldehyde 3 phosphate (aldose)
Glyceraldehyde 3-P C + dehydrogenase

O~ P + CH - OH + NADH+ H CH2- O- P 1,3-Biphosphoglycerate 34

(7) S dung trc tiep goc (~P) cua c chat e TL ATP (phosphoryl hoa mc c chat, khong qua chuoi HH) Enzyme xt la phosphoglycerate kinase 2 ATP O C OCH - OH + ATP CH2- O- P 3-Phosphoglycerate
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GIV : B/oi 2 Glycerate-3-P 2 Pyruvate (p 8-9-10, TL 2 ATP) (8) Phan ng ong phan hoa chuyen goc P t C3 len C2. Enzyme xuc tac la phosphoglycerate mutase. (9) P kh nc vi s xuc tac cua enolase co s sap xep lai mach noi trong noi bo ph/t tao (~ P) O C CH OH CH2- O- P 3-Phosphoglycerate OP-glycerate mutase O C CH O- P CH2- OH 2-Phosphoglycerate OH2O Enolase C O OCH - O~ P CH2 P.enol36 pyruvate

Phosphoglycerate C O~ P kinase + ADP CH - OH CH2- O- P 1,3-Diphosphoglycerate

(10) P thanh lap ATP lan th hai trong ng phan vi s xuc tac cua pyruvatekinase SFTG quan trong PYRUVATE O C OO C OC=O CH3 Pyruvate

G V : Kh 2 Pyruvate 2 Lactae (p 11) (s dung 2 NADH+H+ t GIII (ngheo O2) ONADH + H+ NAD+ Lactatedehydrogenase NADH + H+ (u O2) NAD+

ADP

ATP

O C C=O CH3 Pyruvate

O C OCH - OH CH3 Lactate

Pyruvate kinase CH - O~ P CH2 Phosphoenolpyruvate

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Ln men r u :

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Bang 3.1: NL giai phong t tien trnh FEM

P/ (6) (7) (10) (1) (3) Enzyme xuc tac Glyceraldehyde 3-P dehhdrogenase P-glyceratekinase Pyruvate kinase Hexokinase P-fructokinase Phng thc tao noi ~P Qua chuoi HH mo bao oxy hoa 2NADH + H+ oxy hoa mc c chat oxy hoa mc c chat So ATP c thanh lap Tieu hao ATP Tieu hao ATP So ATP con lai So ATP 6 2 2 10 1 1 8

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Ghi chu: trong ieu kien mo bao ngheo oxygen, pyruvate se s dung NADH + H+ cua p/ (6) e hon nguyen thanh lactate, do o so ATP con lai se la 2.

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5. S OXY HOA HAO KH GLUCOSE

(TRICARBOXYLIC ACID CYCLE, KREBS CYCLE)

- ay la con ng chung cua s oxy hoa cac chat hu c e tao ra ATP cung cap cho cac hoat ong cua c the, bi v glucose (t glucid), acid beo (t lipid) va amino acid (t protein) khi thoai bien eu dan en ACETYL CoA. - Chu trnh nay xay ra trong phan khuon ty the nham oxy hoa ACETYL CoA thanh CO2 + H2O + giai phong toan bo nang lng d tr.
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5.1. S KH CARBOXYL-OXY HOA PYRUVATE ACETYL CoA Phan ng tong quat : O NAD+ NADH + H+ C OO C=O Pyruvatedehydrogenase CH3-C ~S-CoA + CO2 CH3 Complex (E1, E2 ,E3), ACETYL CoA CoASH Pyruvate
Pyruvate dehydrogenase complex : E1: pyruvate decarboxylase (vit.B1) E2: Dihydrolipoyl transacetylase (lipoic acid) E3: Dihydrolipoyl dehydrogenase (FP5-FAD)

O CH3-C-COOPyruvate CO2 TPP E1 OH CH3-C TPP H

CH3-C ~S-L-SH S-acetyl lipoate E2 SH S L S L SH

CoASH

O CH3-C ~S-CoA
ACETYL CoA

E3 FADH2 NAD+

FAD NADH + H+ (vao chu i ho hap)

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Tac ong cua mot so loai thuoc c che cac enzyme Mepacrin cua chu trnh Krebs
Morphin Salicylate

Streptomycin Cocain Salicylate

Fluoarocetate

Morphin Thuoc te Thuoc ngu

Tetracyclin Aureomycin Salicylate

Hnh 2.8 : CHU TRNH KREBS

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(1) Ph n ng k t h p c a acetyl CoA (s n ph m s b oxy hoa) v i oxaloacetate e thanh l p citrate vi s xuc tac cua citrate synthetase

(2) Citrate bien oi thanh isocitrate qua trung gian cisaconitate :

Citrate synthetase Cis-aconitase

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(3) (4). S oxy hoa isocitrate, sau o la s kh carboxyl e thanh lap -ketoglutarate, enzyme xuc tac la isocitrate dehydrogenase va decarboxylase

(5) Phan ng kh carboxyl -oxy hoa -ketoglutarate vi s xuc tac cua -ketoglutarate dehydrogenase complex (tng t nh oi vi pyruvate) : can s tham gia cua TPP, lipoate, NAD+ va CoA.SH (3ATP)

(3)

(3ATP) (4)

(3)
+ NAD+

(4)

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(6) S kh noi thioester cua succinyl -CoA, nang lng giai phong c a vao mot noi phosphate cao nang cua GTP e sau o thanh lap 1 ATP. ATP

(7) Phan ng oxy hoa succinate bi FP2 succinate dehydrogenase, vi CoE la FAD :

(2ATP)
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(8), (9) Phan ng hydrate hoa fumarate e thanh lap malate va tiep theo la s oxy hoa malate e cho ra san pham oxaloacetate :

Bang 2-2 : S ATP c giai phong t chu trnh Krebs

STT Enzyme xuc tac P/ 3 P/ 5 P/ 6 P/ 7 P/ 9
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(8)

(9)

(3ATP)

Phng thc sinh noi So ATP (~P) t/lap. oxy hoa NADH + H+ 3 Isocitrate dehydrogenase trong chuoi ho hap 3 P/h p -ketoglutarate oxy hoa NADH + H+ trong chuoi ho hap dehydrogenase Phosphoryl hoa mc c chat -> GTP oxy hoa FADH2 trong chuoi ho hap oxy hoa NADH + H+ trong chuoi ho hap Tong cong 1 2 3 12
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Succinate thiokinase Succinate dehydrogenase Malate dehydrogenase

Fumarase

Malate dehydrogenase

6. CON NG HEXOSE MONOPHOSPHATE (HMP pathway, Pentose phosphate cycle) Muc ch : Oxy hoa trc tiep Glu-6-P (khong phosphoryl hoa lan th hai goi la con ng HMP). NADPH+H+ : cung cap cac cap H cho cac phan ng tong hp chat can H (tong hp acid beo, cholesterol, cac hormone steroid ). San pham pentose-5-P c s dung e tong hp cac nucleotide acid nucleic. Neu khong s dung th cac pentose 5-P se bien oi e tong hp tr lai Fru-6-P Glu6-P ten goi chu trnh pentose phosphate.
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Phan ng tong quat : 3 Glu-6-P + 6 NADP+ Hai giai oan phan ng : 2Glu-6-P + Gly-3-P + 3CO2 + 6 (NADPH + H+)

G oxy hoa trc tiep 3 phan t Glu-6-P

6(NADPH+H+ ) va + 3 p/t ribulose-5-P (Ru5P), (P/ 1-2 &3)

G bien oi 3 p/t Ru5P 2 Fructose-6-P (F6P) +

Glyceraldehyde-3-P (GAP)(P/ 4-5-6-7&8)
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GIAI OAN OXY HOA P 1 : oxy hoa tr c ti p glucose 6-phosphate : Moi vong chu ky pentose s dung ong thi 3 pt Glu-6P :

P 2 : kh vong tao phan t dang thang 6-phosphogluconate O C- OH H- C- OH HO-C- H H- C- OH H- C- OH CH2O- P 6-Phosphogluconate

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+ NADPH+H+ CH O- P CH2O- P 2 + NADP+ H 1 =O 1 OH OH Glucose 6-P OH OH OH dehydrogenase OH OH 6-PhosphogluconoGlucose 6-P lactone 63

CH2O- P OH 1 =O

H+ H2O 6-Phosphogluconolactonase

OH

OH 6-Phosphoglucono lactone

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P 3 :phan ng kh carboxyl (C1) va oxy hoa (C3) thanh lap pentose 5-phosphate (Ru5P) O C1- OH H- C- OH HO-C3- H H- C- OH H- C- OH CH2O- P 6-Phosphogluconate NADPH+H+ +NADP+ + CO2 CH2- OH C=O H- C- OH H- C- OH CH2O- P Ribulose-5phosphate (Ru5P)
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7. S

TN SINH GLUCOSE (Gluconeogenesis)

th

T ng h p glucose t lactate, glycerol v aminoacid; nhai l i l propionate.

Cung c p glucose cho c th , c bi t l no v h ng c u (v 2 c quan ny ch s d ng nng l ng t ng, khng dng m ) khi ngu n glucid cung khng trong kh u ph n. C ch tn sinh ng m ph ng theo cc p/ i ng c ng phn EM. Tuy nhin nh ng g/ m p/ ng phn khng thu n ngh ch th tn sinh ng ph i i theo ng vng.
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6-Phosphogluconatedehydrogenase

3 giai o n tn sinh ng khng theo p/ ngh ch c a ng phn (1) PYRUVATE PHOSPHO ENOL PYRUVATE T N S I N H N G
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(2) FRUCTOSE 1,6 - BIPHOSPHATE

FRUCTOSE 6-P

(3) GLUCOSE 6-PHOSPHATE

GLUCOSE

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Hnh 2.12 : S

I U HOA TRAO

I NG

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