Kreb's cycle Flashcards
Where does the Krebs cycle take place in eukaryotes ?
in the mitochondria
What are the other names for the kreb’s cycle ?
- tricarboxylic acid cycle
- citric acid cycle
Describe how energy is extracted from food
Stage 1 - Large molecules broken down into smaller units. No useful energy is captured
Stage 2 - Small molecules are degraded into a few simple units that play a role in central metabolism. Some ATP is generated ~ 5-10%
Stage 3 - ATP (~90-95%) is produced from the complete oxidation of simple units by the final common pathways for oxidation of fuel. ~90-95%
Briefly describe the Krebs cycle
- it is a final common pathway for the oxidation of all fuel molecules
- it has a catabolic role and involves the degradation of molecules for energy production
- it has an anabolic role and several biosynthetic pathways use the citric acid cycle intermediates as starting materials
- it is an amphibolic pathway
What is meant by an amphibolic pathway ?
it has both catabolic and anabolic roles
What is the overall stoichiometry of the krebs cycle ?
Acetyl CoA + 3 NAD+ + FAD + GDP + Pi + 2 H2O > 2 CO2 + 3 NADH + FADH2 + GTP + 2H+ + HSCoA
Where do humans get 90% of their energy from ?
in humans over 90% of energy is provided by the krebs cycle and oxidative phosphorylation
How many turns of the krebs cycle does Acetyl CoA oxidation require ?
Acetyl CoA oxidation requires 2 turns of the krebs cycle
Describe reaction 1 of the krebs cycle
- condensation of Acetyl CoA with oxaloacetate takes place in the mitochondria and this makes citrate
- it is catalysed by citrate synthase
- it is a rate limiting step
- inhibited by fluoroacetate
Describe reaction 2 of the krebs cycle
- isomerisation of citrate to isocitrate (the OH group is moved from the C3 position to C2)
Describe reactions 3 and 4 of the krebs cycle
- oxidative decarboxylations
- step 3 is carried out by isocitrate dehydrogenase which is an NAD+ specific enzyme
- NADH and CO2 is generated
- this is a rate determining step
- step 4 is carried out by α-ketoglutarate dehydrogenase which is a multienzyme complex containing thiamine and CoA
- NADH and CO2 is generated
- this is another control point of the krebs cycle
How many rate determining steps are there in the krebs cycle ?
3
Describe reaction 5 of the krebs cycle
- the high energy bond of succinyl CoA is cleaved by the enzyme succinyl CoA synthetase
- GTP is generated by substrate level phosphorylation
- GTP + ADP <> ATP + GDP
Describe reactions 6,7 and 8 of the krebs cycle
- regeneration of oxaloacetate
- succinate is oxidised to fumarate by succinate dehydrogenase which is a membrane bound enzyme directly associated with the electron transport chain
- FAD is the electron acceptor and so FADH2 is produced
- fumarate is hydrated by fumarase to produce L-Malate
- malate then undergoes oxidation by malate dehydrogenase to regenerate oxaloacetate and NADH is produced
- the ΔG0 is positive and so the reaction is driven by the utilisation of products
Describe the regulation of the krebs cycle
- hormonal control e.g. insulin and glucagon
- phosphorylation state of enzymes
- feedback inhibition of enzymes
- feedforward stimulation of enzymes
- allosteric regulation of enzymes :
- less ATP and less electrons = positive allosteric effector
- lots of ATP and NADH = negative allosteric effector
