Chu trnh acid citric (Chu trnh Kreb)

Bs. Chi Mai

Chu trnh acid citric

cc sinh vt i kh, pyruvat (to thnh t ng phn) b oxy ha thnh CO2 and acetyl-CoA vi s tham gia ca coenzyme A S oxy ha acetyl CoA tip theo bng mt lot cc phn ng thuc chu trnh acid citric

c im v ngha:

Xy ra trong ty th, trong iu kin i kh D ha i kh ca carbohydrat, lipid, and acid amin u kt thc chu trnh acid citric.

Oxy ha acetyl-CoA to thnh t chuyn ha ca c 3 nhm cht trn

Cung cp nhiu nng lng Sn phm trung gian ca chu trnh acid citric l im bt u cho nhiu con ng sinh tng hp

Chu trnh acid citric

Chu trnh acid citric

Oxy ha c kim sot

Cc cht c oxy ha cc bc khc nhau in t c vn chuyn ti O2

Tng t vic t chy cc cht hu c, sinh ra CO2 v H2O v nhit

Nng lng gii phng ra ch yu c gi li khi NAD+ v ubiquinone (Q) c kh thnh NADH v ubiquinol (QH2) S oxy ha cc coenzym dng kh ni trn sinh ra nhiu ATP qua s vn chuyn electron v s phosphoryl oxy ha.

Cn gi l:

Chu trnh acid tricarboxylic (TCA) (do cc cht trung gian l tricarboxylat) Chu trnh Krebs (Tn nh ha sinh Hans Krebs)

Cc phn ng

Chu trnh

Ti to oxaloacetat, cht m u chu trnh, bc cui ca chu trnh Chu trnh l cc phn ng enzym, c th xc tc s chuyn ha ca v tn nhm acetyl 2 carbon i vo chu trnh khng phi l 2 carbon mt i di dng CO2

Carbon i vo:

Gm 8 phn ng xc tc bi enzym
Vn chuyn 4 i in t Sinh ra cc phn t giu nng lng:

Phn ln nng lng gii phng ra c gi di dng coenzym dng kh NADH v FADH2 (hoc QH2) Oxy ha cc coenzym dng kh trong chui h hp sinh ra ATP t ADP v Pi qua s phosphoryl ha

9 ATP c th to thnh t 4 i e chuyn n O 2

Phn ng 5 l phosphoryl ha mc c cht sinh ATP hay GTP ty thuc loi t bo Acetyl-CoA + 3 NAD+ + FAD + GDP + Pi + 2 H2O 2 CO2 + 3 NADH + FADH2 + CoA + GTP + 3 H+

Phn ng tng qut:

To acetyl-CoA
NH2 N N OH HS CH2 CH2 H N C O CH2 CH2 H N C O C H CH3 C CH3 CH2 O O P O O O P O O CH2 H H O O P O O OH N H H O N

Khng thuc chu trnh nhng cn a ra trc tin Bc 1: pyruvat i vo trong ty th

t bo i kh, tt c cc enzym ca chu trnh acid citric nm trong ty th Ty th c bao bc bi mt mng kp Pyruvat qua lp mng ngoi nh cc knh a nc-cc protein xuyn mng (porins) Pyruvate translocase l protein ca mng trong ty th, vn chuyn pyruvat t khoang gia 2 mng vo trong lng ty th (mitochondrial matrix)

Chuyn pyruvat thnh acetyl-CoA

Kh carboxyl oxy ha

Mt lot 5 phn ng
Khng thun nghch C ch rt phc tp

Xc tc bi phc hp a enzym v cofactor

Phc hp Pyruvate dehydrogenase

Phc hp a enzym trong lng ty th Cha nhiu phn t ca 3 enzym lin kt khng ng ha tr v 5 coenzym

E1 v E3 bao quanh li chui 24-60 E2

(s chui ph thuc loi t bo)

Phn ng tng qut:

CH3C(O)CO2- + NAD+ + CoASH CH3C(O)-SCoA + NADH + CO2

1. To citrat
CO2 C CH2 CO2 O S CoA O

C CH3

Oxaloacetat phn ng vi acetyl-CoA to citrat v coenzyme A

H2O

H+

Khng thun nghch

CO2 CH2 HO C CH2 CO2 CO2 + HS-CoA

Enzym = citrate synthase

Citrate synthase

Dime gm 2 tiu n v ging ht nhau Changes in conformation

Binding of oxaloacetate Domains move closer to form binding site for acetyl-CoA

Formation of intermediate
Enzyme closes around intermediate

Prevent side reactions by shielding thiol ester linkage of acetyl-CoA from hydrolysis by solvent Intermediate hydrolyzed by bound water molecule

Enzyme opens and products leave active site

2. ng phn citrat thnh isocitrat

CO2 CH2 HO C CH2 CO2 CO2

Citrate c nhm alcol C3

Khng th b oxy ha thnh acid cetonic B oxy ha d dng

H2O

Isocitrate c nhm alcol C2

C ch:

CO2 H2O CH2 C CH CO2 CO2 HO

CO2 CH2 HC CH CO2 CO2

Bc 1: loi H2O to dn xut trung gian alken (cis-aconitat) Bc 2: hp nc to isocitr Cn gi aconitat hydratase

Enzym = aconitase

3. Kh carboxyl oxy ha isocitrat to a-ketoglutarat

CO2 CH2 HC HO CH CO2

Phn ng oxy ha u tin trong 4 phn ng oxy ha

NAD+ l tc nhn oxy ha Bc 1: alcol b oxy ha bi chuyn H- t C2 cho NAD+

CO2

C ch:

NAD+

NADH + H+

Cht trung gian = oxalosuccinat, acid bketo khng n nh Phn t NADH th nht c to thnh

CO2 CO2 CH2 HC O C CO2 CO2 H+ O CH2 CH2 C CO2 CO2

Bc 2: cht trung gian kh carboxyl v tr b to a-keto acid Phn t CO2 u tin c to thnh Khng thun nghch L 1 bc hn ch tc ca chu trnh

Enzym = isocitrate dehydrogenase

4. Kh carboxyl oxy ha a-ketoglutarat to succinyl-CoA

CO2 CH2 CH2 O C CO2

c xc tc bi phc hp a enzym a-ketoglutarat dehydrogenase

a-ketoglutarat dehydrogenase (E1) Dihydrolipoamide succinyltransferase (E2) Dihyrdolipoamide dehydrogenase (E3)

HS-CoA NAD+

Tng t phn ng chuyn pyruvat thnh acetyl-CoA xc tc bi phc hp pyruvate dehydrogenase

Coenzym tng t C ch tng t

CO2

NADH

CO2 CH2 CH2 O C S-CoA

Sn phm cha lin kt thioeste giu nng lng Bc iu ha then cht ca chu trnh acid citric To phn t NADH th hai Sinh ra phn t CO2 th hai

5. Chuyn succinyl-CoA thnh succinat

CO2 CH2 CH2 O C S-CoA

Phosphoryl ha mc c cht

Ph v lin kt thioeste giu nng lng Nng lng gii phng c bo tn bng tng hp nucleosid triphosphate

GTP ng vt c v ATP thc vt v vi khun

GDP + Pi

GDP ti to li v ATP sinh ra t phn ng ca GTP vi ADP

GTP + HS-CoA

CO2 CH2 CH2 CO2

GTP + ADP GDP + ATP Nucleoside diphosphate kinase

Enzym = succinyl-CoA synthetase

Cn gi succinat thiokinase

C ch ca Succinyl-CoA synthetase

6. Oxy ha succinat to fumarat

CO2 CH2 CH2 CO2

Dehydrogen (mt H2; oxy ha)

c hiu khng gian vi dng trans ca lin kt i Cn gi l phc hp II Nm mng trong ty th

Xc tc bi phc hp succinat dehydrogenase

FAD QH2

Oxy ha alkan i hi tc nhn oxy ha mnh hn NAD+ ( l FAD)

FADH2

FADH2 to ra b oxy ha bi coenzym ubiquinon (Q) to FAD v ubiquinol (QH2)

-O 2C-CH2-CO2 -

H C C O2C

CO2

Cht c ch cnh tranh = malonat

Gn vi v tr hot ng qua nhm carboxylat Khng b dehydrogen

7. Hydrat ha fumarat to L-malat

H C C O2 C H CO2

Phn ng thun nghch c hiu khng gian

1.

H2O

Hp nc vo lin kt i ca fumarat Ch lin kt i dng trans mi phn ng

2.
CO2 HO C CH2 CO2 H

Enzym = fumarase

Cn gi fumarat hydratase

8. Oxy ha L-malat to oxaloacetat

CO2 HO C CH2 CO2 H

NAD+

To phn t NADH th ba Enzym = malat dehydrogenase

NADH + H+

CO2 O C CH2 CO2

Nng lng to thnh trong chu trnh

3NADH (phn ng 3,4,8): 3x3= 9 ATP 1FADH2 (phn ng 6): 1x2= 2ATP 1GTP (phn ng 5):tng ng 1ATP Cng: 12 ATP

iu ha chu trnh acid citric

c iu ha bi cc enzym then cht v c cht tham gia vo chu trnh

S tch ly citrat lm chm qu trnh ng phn/to pyruvat

Cn ph thuc s cung cp acetyl-CoA (t pyruvat), NAD+, FAD, v ADP Cc enzym c iu ha trong chu trnh acid citric l:

Citrate synthase (phn ng1)

B c ch d lp th bi nng cao ca citrat, succinyl-CoA, NADH, ATP

Isocitrate dehydrogenase (phn ng 3)

c kch thch bi ADP, NAD+, v Ca2+ (c) B c ch bi ATP v NADH B c ch bi ATP, GTP, NADH v succinyl-CoA

a-Ketoglutarate dehydrogenase (phn ng 4)

C 3 enzym trn xc tc cc phn ng

nhng im r quan trng trong chuyn ha