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Lecture notes of 11 pages for the course Membrane and cellular Biochemistry at QMUL
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Characteristics of oxidative phosphorylationLearning objectives:
1. Outline the role of mitochondria in energy metabolism in eukaryotes
2. Summarise how glycolytic ATP production is coupled to the mitochondrial metabolism
3. Outline the features of the tricarboxylic acid (TCA) cycle in the mitochondrial matrix that are critical for energy conversion
4. Describe how other catabolic pathways are linked to the TCA cycle
5. Summarise the 2 steps in oxidative phosphorylation
6. Define the terms ‘standard redox potential’ and ‘redox coupled’
7. Based on the ‘standard redox potential’ and ‘redox couple’ discuss the different contributions of these reduced
coenzymes to oxidative phosphorylation
Overview of carbohydrate metabolism in eukaryotic cells
NADH is energy rich
Amount of NAD in cytosol is low
If cell runs fast glycolysis, it will quickly use the ATP and all the NAD will be NADH and then glycolysis stops quickly if there
is nowhere to put the NADH
- this is why muscles get tired wen exercise
- Anaerobic glycolysis in skeletal muscle as ran out of NAD
there is a couple of ways to generate NAD
- One way is fermentation (in yeast ethanol)
- In human muscle get lactate
, Catabolic oxidative glucose metabolism: glycolysis
Glycolysis occurs in the cells cytoplasm
Activate glucose – 1 phosphorylation event
Glucose then isomerised to fructose 1,6-bisphosphate
Another phosphorylation
- Used 2 ATP molecules
Split fructose 1,6-bisphosphate into two 3 C molecules
Energetic step- phosphorylation but not using ATP, which means get a high energy compound without using ATP
- 2 high energy phosphates
This step, get energy back
- Phosphorylation of ADP to ATP twice
Phosphate group moves to the 2nd carbon to produce a high energy phosphate (phosphoenol-pyruvate)
Phosphoenol-pyruvate to pyruvate, convert 2 ADP to 2 ATP
Overall, use 2 ATP molecules in the beginning but gain 4 ATP at the end.
Coupling between glycolysis and mitochondrial oxidative metabolism- How is NADH moved into the mitochondria?
NADH is transported indirectly across the IMM by 2 shuttle mechanisms:
1. Malate-aspartate shuttle
2. Glycerol phosphate shuttle
This is the glycerol phosphate shuttle as glycerol is he molecule reduced in the cytosol
This delivers 2 electrons to form either NADH or FADH 2 in the matrix.
Electrons in the NADH are used to reduce DHAP to glycerol 3- p (shown in red)
Glycerol 3-p is moved into the Intermembrane space
Glycerol 3-phosphate dehydrogenase can re-oxidise glycerol 3-p to DHAP
G3PDH takes the 2 electrons from glycerol 3-p and moves to the inner part of the membrane to reduce FAD to FADH 2
No molecules have been moved physically across the membrane, just transferred electrons through the molecules by
oxidising a molecule in the IMM and reducing a molecule in the OMM
NAD is regenerated and goes back to help glycolysis run.
Electrons on FAD are less powerful than electrons on NADH
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