Electron Transport and Oxidative Phosphorylation

It all reduces down to water.

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

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

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

4 Complexes
proteins in specific order Transfers 2 electrons in specific order
Proteins localized in complexes
Embedded in membrane Ease of electron transfer 2 H+ + 2 e- + O2 -H 2O

Electrons ultimately reduce oxygen to water

Electron Transport Chain

Complex 1
Has NADH binding site
NADH reductase activity
NADH - NAD+

NADH ---> FMN--->FeS---> ubiquinone ubiquinone ---> ubiquinone H2 4 H+ pumped/NADH

Electron Transport Chain

Complex II
succinate ---FADubiquinone
Contains coenzyme Q FADH2 binding site
FAD reductase activity FADH2 -- FAD

Electron Transport Chain

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

Electron Transport Chain

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

Totals
Proton gradient created as electrons transferred to oxygen forming water
10 H+ / NADH 6 H+ / FADH2

Electron Transport Chain

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

Totals
NADH
10 H+ X 1 ATP = 2.5 ATP 4 H+ FADH2 6 H+ X 1 ATP = 1.5 ATP 4 H+

Total ATP from mitochondrial matrix

Pyruvate dehydrogenase
NADH .2.5 ATP

Krebs
3 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)

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

Glycerol Phosphate shuttle

http://courses.cm.utexas.edu/jrobertus/ch339k/overheads-3/ch19_glycerol-shuttle.jpg

Glycerol phosphate shuttle

In muscle and brain Each NADH converted to FADH2 inside mitochondrion
FADH2 enters later in the electron transport chain Produces 1.5 ATP

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 glycoysis2.0 ATP From pyruvate and Krebs
12.5 ATP X 2 per glucose ..25.0 ATP
Total = 30.0 ATP/ glucose

Malate Aspartate Shuttle

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

Malate Aspartate Shuttle in cytosol

In liver and heart NADH oxidized while reducing oxaloacetate to malate
Malate dehydrogenase

Malate crosses membrane

Malate Aspartate Shuttle in matrix

Malate reoxidized to oxaloacetate
Malate dehydrogenase NAD+ reduced to NADH

NADH via electron transport yields 2.5 ATP

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

Summary
Total ATP / glucose
Muscle and brain
Uses glycerol phosphate shuttle

30.0 ATP

Heart and liver

Uses malate aspartate shuttle

32.0 ATP