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BIOENERGETICSYulia Suciati
Krebs Cycle, Electron Transport and Oxidative Phosphorylation
Yulia Suciati
SIKLUS KREBS
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.
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:
SIKLUS ASAM SITRAT
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
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
SIKLUS ASAM SITRAT
• Step 4: A Second Oxidative Decarboxylation Step
• This step is performed by a multi-enzyme complex, the a-Ketoglutarate Dehydrogenation Complex
SIKLUS ASAM SITRAT
• Step 5: Substrate-Level Phosphorylation
SIKLUS ASAM SITRAT
• Step 6: Flavin-Dependent Dehydrogenation
SIKLUS ASAM SITRAT
• Step 7: Hydration of a Carbon-Carbon Double Bond
SIKLUS ASAM SITRAT
• Step 8: A Dehydrogenation Reaction that will Regenerate Oxaloacetate
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.
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
FOSFORILASI OKSIDATIF
The figure is found at http://plaza.ufl.edu/tmullins/BCH3023/cell%20respiration.html (December 2006)
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
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 from matrix
Succinate-CoQ oxidoreductase (complex II)
• Succinate-CoQ oxidoreductase– succinate dehydrogenase is a component– No protons transported– FAD, FeS serve as intermediate electron
carriers
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 deposited in intermembrane space, 1 e- to Cyt c, 1 e- to Qn
• Qn with 2 e- takes 2 H+ from matrix.
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 occursin matrix, thus removing 4 H+
Chemiosmosis
• Chemiosmosis - Movement of protons from high (IMS) to low conc (matrix) used to drive ATP synthesis
• electrochemical gradient - electrical and chemical potential• Electron transport drives generation of H+ gradient
– +0.14V electrical potential– 1.4 pH unit difference– G=~21 kJ/mole H+
• H+ gradient drives ATP synthesis
The figure is found at http://plaza.ufl.edu/tmullins/BCH3023/cell%20respiration.html (December 2006)
ATP synthase
inner mitochondrial membrane
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
small molecule shuttles
• molecules must be transported to and from matrix
• ATP-ADP translocase exports ATP, imports ADP - movement of more negative ATP from matrix dissipates 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
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 ATPper pair of electrons)
Malate – Aspartate Shuttle
• http://courses.cm.utexas.edu/emarcotte/ch339k/fall2005/Lecture-Ch19-2/Slide14.JPG
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
Inhibitors
• Electron flow can be inhibited by POISONS
• Useful in lab to control entry and exit points for electron transport studies
• Proton gradients are dissipated by DNP & FCCP, inhibiting ATP synthesis
• Thermogenin in “brown adipose tissue” dissipates proton gradient togenerate heat
The figure is found at http://departments.oxy.edu/biology/Franck/Bio222/Lectures/March23_lecture_shuttles.htm (December 2006)
Uncoupling proteins
(UCP)
= separate RCH from
ATP synthesis
(the synthesis is interrupted)
energy from H+ gradient is
released as a heat
SEMOGA BERMANFAATYS 2011