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Harliansyah, Ph.D
Human Blok Systems
Dental Medicine Program
YARSI UNIVERSITY @ 2012
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Mitochondria outer membrane relatively permeable
inner membrane permeable only to those things with
specific transporters Impermeable to NADH and FADH2 Permeable to pyruvate
Compartmentalization
Kreb's and -oxidation in matrix Glycolysis in cytosol
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Most energy from Redox electrons during metabolic reactions sent to NAD
and FAD Glycolysis
In cytosol
produces 2 NADH
Pyruvate dehydrogenase reaction In mitochondrial matrix
2 NADH / glucose Krebs
In mitochondrial matrix
6 NADH and 2 FADH2 / glucose
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Oxidative Level Phosphorylation
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Electron Transport Chain Groups of redox proteins
On inner mitochondrial membrane
Binding sites for NADH and FADH2 On matrix side of membrane
Electrons transferred to redox proteins
NADH reoxidized to NAD+
FADH2
reoxidized to FAD
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4 Complexes proteins in specific order
Transfers 2 electrons in specific order
Proteins localized in complexes Embedded in membrane
Ease of electron transfer
Electrons ultimately reduce oxygen to water
2 H+
+ 2 e-
+ O2 --
H2O
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Electron Transport Chain
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Complex 1 Has NADH binding site
NADH reductase activity
NADH - NAD+
NADH ---> FMN--->FeS---> ubiquinone
ubiquinone ---> ubiquinone H2 4 H+ pumped/NADH
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Electron Transport Chain
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Complex II succinate ---FADubiquinone
Contains coenzyme Q
FADH2 binding site
FAD reductase activity
FADH2 -- FAD
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Electron Transport Chain
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Complex III ubiquinone - ubiquinone ox
while cyt C gets reduced
Also contains cytochromes b proton pump 4H+
Adds to gradient
8 H+ / NADH
4 H+
/ FADH2
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Electron Transport Chain
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Complex IV reduction of oxygen
cytochrome oxidase
cyt a+a3 red ---> oxidized state oxygen ---> water
2 H+ + 2 e- + O2 -- 2 H2O
transfers e- one at a time to oxygen
Pumps 2H+ out
Total of 10 H+ / NADH
Total of 6 H+ / FADH2
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Totals Proton gradient created as electrons transferred to
oxygen forming water
10 H+ / NADH
6 H+ / FADH2
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Electron Transport Chain
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Generation of ATP Proton dependant ATP synthetase
Uses proton gradient to make ATP
Protons pumped through channel on enzyme From intermembrane space into matrix
~4 H+ / ATP
Called chemiosmotic theory
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ATP
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Sources of ATP
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TotalsNADH
10 H+ X 1 ATP = 2.5 ATP
4 H
+
FADH2
6 H+X 1 ATP = 1.5 ATP
4 H+
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Total ATP from mitochondrial matrix Pyruvate dehydrogenase
NADH .2.5 ATP
Krebs3 NADH X 2.5 ATP/NADH .7.5 ATP
FADH2 X 1.5 ATP / FADH2.1.5 ATP
GTP X 1 ATP / GTP ..1.0 ATP(from a separate reaction)
Total .12.5 ATP
(Per glucose = X 2 = 25 ATP)
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Review of ATP Production
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What about NADH from glycolysis? NADH made in cytosol
Cant get into matrix of mitochondrion
2 mechanisms In muscle and brain
Glycerol phosphate shuttle
In liver and heart
Malate / aspartate shuttle
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Glycerol Phosphate shuttle
http://courses.cm.utexas.edu/jrobertus/ch339k/overheads-3/ch19_glycerol-shuttle.jpg
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Glycerol phosphate shuttle In muscle and brain
Each NADH converted to FADH2 insidemitochondrion
FADH2 enters later in the electron transport chain
Produces 1.5 ATP
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Total ATP per glucose in muscle and brain Gycerol phosphate shuttle
2 NADH per glucose - 2 FADH2
2 FADH2
X 1.5 ATP / FADH2.3.0 ATP
2 ATP in glycoysis 2.0 ATP
From pyruvate and Krebs
12.5 ATP X 2 per glucose ..25.0 ATP
Total = 30.0 ATP/ glucose
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Malate Aspartate Shuttle
http://courses.cm.utexas.edu/emarcotte/ch339k/fall2005/Lecture-Ch19-2/Slide14.JPG
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Malate Aspartate Shuttle
in cytosol In liver and heart
NADH oxidized while reducing oxaloacetate to malate
Malate dehydrogenase Malate crosses membrane
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Malate Aspartate Shuttle
in matrix Malate reoxidized to oxaloacetate
Malate dehydrogenase
NAD+
reduced to NADH NADH via electron transport yields 2.5 ATP
Mlate Aspartate
Shuttle
in cytosol
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Total ATP per glucose in liver and heart Malate Aspartate Shuttle
2 NADH per glucose - 2 NADH
2 NADH X 2.5 ATP / NADH5.0 ATP
2 ATP from glycolysis..2.0 ATP
From pyruvate and Krebs
12.5 ATP X 2 per glucose ..25.0 ATP
Total = 32.0 ATP/ glucose
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Summary Total ATP / glucose
Muscle and brain 30.0 ATP Uses glycerol phosphate shuttle
Heart and liver 32.0 ATP Uses malate aspartate shuttle