siklus krebs-rp 1011 ys

7/29/2019 Siklus Krebs-rp 1011 Ys

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Krebs Cycle, Electron Transport

and Oxidative Phosphorylation

Yulia Suciati


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SIKLUS KREBS


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SIKLUS ASAM SITRAT

Terjadi didalam matriks mitokondria

Proses ini bersifat aerobik

Fungsi utama siklus asam sitrat (siklus krebs)a/ bekerja sbg lintasan akhir bersama untuk

oksidasi KH, Lipid, Protein.

Glukosa, as. Lemak, AA, dimetab. Mjd asetil

KoA atau senyawa antara di SAS.


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SIKLUS ASAM SITRAT

Step 1: Condensation

In step 1 of the Krebs cycle, the two-carbon

compound, acetyl-S-CoA, participates in a

condensation reaction with the four-carbon

compound, oxaloacetate, to produce citrate:


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Step 2. Isomerization of Citrate

step 2 involves moving the hydroxyl group in the

citrate molecule so that we can later form an

a-keto acid


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SIKLUS ASAM SITRAT

Step 3: Generation of CO2 by an NAD+ linked

enzyme

The Krebs cycle contains two oxidative

decarboxylation steps; this is the first one

The reaction is catalyzed by the enzyme

Isocitrate dehydrogenase


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SIKLUS ASAM SITRAT

Step 4: A Second Oxidative Decarboxylation

Step

This step is performed by a multi-enzyme

complex, the a-Ketoglutarate

Dehydrogenation Complex


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Step 5: Substrate-Level Phosphorylation


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Step 6: Flavin-Dependent Dehydrogenation


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Step 7: Hydration of a Carbon-Carbon Double

Bond


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Step 8: A Dehydrogenation Reaction that will

Regenerate Oxaloacetate


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HASIL AKHIR S.A.S

12 molekul ATP terbentuk pada setiap kali

putaran S.A.S

Sejumlah ekuivalen pereduksi akan dialihkan

kpd rantai pernafasan dlm membran dalam

mitokondria.


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VITAMIN YG PENTING PD S.A.S

Riboflavin, dlm bentuk FAD (Flavin Adenin

Dinukleotida)

Niasin, dlm bentuk NAD (Nikotinamide

Dinukleotida)

Tiamin, dlm bentuk TPP (Tiamin Pirophosfat)

Asam pantotenat, sbg bag. dr Koenzim A


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FOSFORILASI OKSIDATIF


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Electron Transport Complexes

4 multiprotein complexes in mitochondrial IM

NADH-CoQ (ubiquinone) oxidoreductase

Succinate-CoQ oxidoreductase

Ubiquinone-cytochrome c oxidoreductase Cytochrome c oxidase - reduction of O2

Contain a variety of prosthetic groups, iron-sulfur clusters

Some subunits encoded by mitochondrial DNA


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NADH-CoQ (ubiquinone) oxidoreductase (complex I)

2 electrons passed from NADH, through

FMN, FeS intermediate electron carriers to

ubiquinone (coenzyme Q)

Ubiquinone - lipid soluble electron carrier

Proton pumps transport 4 H+ from matrix to

intermembrane space per pair of electrons

Spatial organization important - protons

used in reduction of ubiquinone come frommatrix


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Succinate-CoQ oxidoreductase (complex II)

Succinate-CoQ oxidoreductase

succinate dehydrogenase is a component

No protons transported

FAD, FeS serve as intermediate electron

carriers


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Ubiquinone-cytochrome c

oxidoreductase (complex III)

Cytochrome c - peripheral protein,

electron carrier

Cytochromes can only accept 1

electron at a time, resulting in Q cycle 2 H+ from 1st Q deposited in

intermembrane space,

1 e- to Cyt c, 1 e- to Qn

2 H+ from 2nd Q depositedin intermembrane space,

1 e- to Cyt c, 1 e- to Qn

Qn with 2 e- takes 2 H+

from matrix.


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Cytochrome c

oxidase

catalyzes reduction of

molecular oxygen

13 subunits

Four protons translocated for

each O2 reduced

Accumulates 4 electrons (Cu+, Fe2+) for

complete reduction before releasing products

or toxic partially-reduced products

O2 + 4 e- + 4 H+ --> 2 H2O occurs

in matrix, thus removing 4 H+


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ATP Synthase

ATP Synthase produces ATP

from ADP & Pi

H+ passage causes conformational changes

(rotation) in F1, leading to release of ATP so

ADP can bind again

about 3 protons per ATP must pass

through ATP synthase

The Big Picture


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The Big Picture


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small molecule shuttles

molecules must be transported to and

from matrix

ATP-ADP translocase exports ATP, imports ADP -

movement of more negative ATP from matrixdissipates electrical potential across membrane,

weakening gradient by 1 H+.

Phosphate translocase uses 1 H+.

cytosolic NADH

DHAP is reduced by NADH to

Glycerol-3-P in muscle

Electrons passed through FAD to Q

is less efficient, but allows transport

against large NADH gradient


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malate-aspartate shuttle

malate-aspartate shuttle used in heart, liver, kidney to

transfer cytosolic reducing equivalents to matrix

No loss in ATP

generation (2.5 ATP

per pair of electrons)


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Malate Aspartate Shuttle

http://courses.cm.utexas.edu/emarcotte/ch339k/fall2005/Lecture-Ch19-2/Slide14.JPG


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ATP yield/glucose

2 ATP - Glycolysis

3-5 ATP from 2 FADH from 2 NADH from glycolysis

5 ATP from 2 NADH from transition reaction 15 ATP from 6 NADH from TCA cycle

2 ATP from 2 GTP from TCA cycle

3 ATP from 2 FADH from TCA cycle

30-32 ATP from complete oxidation of glucose


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Inhibitors

Electron flow can be inhibited by

POISONS

Useful in lab to control entry and

exit points for electron transportstudies

Proton gradients are dissipated by

DNP & FCCP, inhibiting ATP

synthesis Thermogenin in brown adipose

tissue dissipates proton gradient

to

generate heat


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