Carbohydrate metabolism (lecture 24) Flashcards
What are the 3 major pathways in the oxidation of glucose?
Glycolysis
Citric acid cycle
Oxidative phosphorylation
Where does glycolysis happen?
Cytosol
Where does the citric acid cycle happen?
Mitochondria
Where does oxidative phosphorylation happen?
Mitochondria
What is glycolysis?
The use of carbohydrates as fuel
Conversion of glucose to pyruvate
Why is glycolysis important?
Gives us a ready supply of energy that can be used quickly
What are the 3 stages of glycolysis?
1. Investment or priming Glucose --> fructose-1,6-bisphosphate 2. Splitting Fructose-1,6-bisphosphate --> 2 glycerol-3-phosphates 3. Energy conservation or yield Glycerol-3-phosphate --> pyruvate
What happens in the investment stage?
- Glucose –> glucose-6-phosphate
- Glucose-6-phosphate –> fructose-6-phosphate
- Fructose-6-phosphate –> fructose-1,6-bisphosphate
Glucose –> glucose-6-phosphate
Uses enzyme hexokinase
Hexokinase = kinase that phosphorylates hexose sugar to create ATP
Creates a molecule with a large charge - gets repelled by the cell membrane so can no longer escape the cell
ATP is complexed to a magnesium ion - complexes with 2/3 phosphates & protects them from hydrolysis
When ADP is produced Mg+ flies off
Glucose-6-phosphate –> fructose-6-phosphate
Uses the enzyme glucose-6-phosphate isomerase
converts the aldopyranose to a ketofuranose
- Molecule breaks open
- Produces an aldehyde side chain - not stable
- Quickly becomes a ketone
- Oxygen in the ketone group heads towards the other oxygen
- End up with a 5 membered ring - less stable
Almost a mirror image
Doesn’t require ATP
Fructose-6-phosphate –> fructose-1,6-bisphosphate
ATP needed
Enzyme is phosphofructokinase - an allosteric enzyme
Irreversible step
ATP bound to Mg+
Mirror image is formed
2 phosphate groups try to pull the molecule apart
What does bisphosphate mean?
2 phosphate groups but on different carbons
Would be diphosphate if they were on the same carbon
What happens in splitting?
When the single 6-cabon molecule is split into 2 3-carbon molecules
Aldolase breaks the molecule into 2
Produces 2 products which are isomers
What are the 2 products (isomers) produced by splitting?
- Dihydroxyacetone-phosphate
- Glyceraldehyde-3-phosphate
Dihydroxyacetone-phosphate has 2 possible fates
- Can be used in the synthesis of fatty acids
- Be converted into its other isomer
Triosephosphate isomerase converts DHAT to GA3P
What happens in the yield stage?
Pyruvate is formed
- Glyceraldehyde-3-phosphate –> 1,3-bisphosphoglycerate
- 1,3-bisphosphoglycerate –> 3-phosphoglycerate
- 3-phosphoglycerate –> 2-phosphoglycerate
- 2-phosphoglycerate –> phosphoenolpyruvate
- phosphoenolpyruvate –> pyruvate
Yield stage
1) Glyceraldehyde-3-phosphate –> 1,3-bisphosphoglycerate
‘The magic step’
Doesn’t require ATP
Catalysed by GAPDH - glyceraldehyde-3-phosphate dehydrogenase
• Takes NAD+ & generates reducing power (NADH + H+)
• Takes inorganic phosphate to generate 1,3-bisphosphoglycerate
Yield stage
2) 1,3-bisphosphoglycerate –> 3-phosphoglycerate
Production of the first ATP by substrate level phosphorylation
1,3-bisphosphoglycerate is a highly charged & a high energy molecule
• Phosphoglycerate kinase catalyses the joining of the phosphate group with ADP to form ATP
• 3-phophoglycerate is produced
Yield stage
3) 3-phosphoglycerate –> 2-phosphoglycerate
Transfer of phosphate to the central carbon
Catalysed by phosphoglycerate mutase
• Mutases move phosphate groups
Yield stage
4) 2-phosphoglycerate –> phosphoenolpyruvate
Increases the energy potential of the molecule by removal of water
Catalysed by enolase
Generates phosphoenolpyruvate – highly charged molecule
Yield stage
5) phosphoenolpyruvate –> pyruvate
Second energy producing reaction
Phosphoenolpyruvate converted to pyruvate by pyruvate kinase
ATP is produced
What is the overall net gain from glycolysis?
Net gain of 2 ATP for every glucose
2 ATP used in the investment stage
• 1 to generate glucose-6-phosphate
• 1 to generate fructose-1,6-bisphosphate
4 ATP generated (2 per G-3-P)
• 1 molecule of glyceraldehyde-3-phosphate then generates 1 ATP by substrate level phosphorylation from GAPDH
• 1 ATP from substrate level phosphorylation from pyruvate kinase