Harliansyah, Ph.

D Human Blok Systems Dental Medicine Program YARSI UNIVERSITY @ 2012

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

Oxidative Level Phosphorylation

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 -- H2O

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

ATP

Sources of ATP

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 (Per glucose = X 2 = 25 ATP)

.12.5 ATP

Review of ATP Production

What about NADH from glycolysis?

NADH made in cytosol
Cant get into matrix of mitochondrion 2 mechanisms In muscle and brain

Glycerol phosphate shuttle Malate / aspartate shuttle

In liver and heart

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 glycoysis 2.0 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

Mlate Aspartate Shuttle in cytosol

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

30.0 ATP

Uses glycerol phosphate shuttle

Heart and liver

32.0 ATP

Uses malate aspartate shuttle