Krebs Cycle Flashcards
Where does the Krebs cycle occur?
Mitochondrial matrix
Give some examples of the cofactors involved
- CoA
- NAD+
- FAD+
- Thiamine pyrophosphate
- Lipoic acid
What is the net reaction for the conversion of pyruvate to acetyl CoA?
Pyruvate + NAD+ + CoA —-> CO2 + NADH + H+ + acetyl CoA
What does the pyruvate dehydrogenase complex consist of?
20-30 copies of pyruvate dehydrogenase
>60 opies of other enzymes
Cofactors
How many copies of pyruvate dehydrogenase are in the complex?
20-30
How many copies of other enzymes are in the complex?
More than 60
Reaction 1: what is it?
What is required?
Acetyl CoA —–> Citrate
Requires citrate synthase
Reaction 2: what is it?
What is required?
Citrate —–> Isocitrate
Requires aconitase
Reaction 3: what is it?
What is required?
Isocitrate —-> α-ketoglutarate
Requires isocitrate dehydrogenase
CO2 and NADH produced
Reaction 4: what is it?
What is required?
α-ketoglutarate —> succinyl-CoA
Requires α-ketoglutarate dehydrogenase
CO2 and NADH produced
Reaction 5: what is it?
What is required?
Succinyl-CoA —-> Succinate
Requires succinate thiokinase
GTP produced
Reaction 6: what is it?
What is required?
Succinate —-> Fumarate
Requires succinate dehydrogenase
FADH2 produced
Reaction 7: what is it?
What is required?
Fumarate —-> L-malate
Requires fumerase and H2O
Reaction 8: what is it?
What is required?
L-malate —> Oxaloacetate
Requires malate dehydrogenase
NADH produced
What is the net yield of Krebs cycle in one turn?
2xCO2, 3xNADH, GTP and FADH2
Per glucose molecule, what is the net yield of the Krebs cycle?
4xCO2, 6xNADH, 2xGTP and 2xFADH2
Per glucose molecule, what is the net yield of the pyruvate dehydrogenase complex?
2xAcetyl CoA, 2xCO2 and 2xNADH
How is the PDH complex regulated?
When the PDH complex is phosphorylated it is inactive, when dephosphorylated it is active
So PDH kinase deactivates it and PDH dephosphatase activates it
Which 2 enzymes regulate the PDH complex?
PDH kinase inhibits it
PDH phosphatase activates it
Other than enzyme activity, how is the PDH complex regulated?
If there’s a high [substrates] present the it is stimulated, if high [products] then inhibited
At what 3 points is the Krebs cycle regulated? What is the regulation linked to?
- Citrate synthase
- Isocitrate dehydrogenase
- α-ketoglutarate dehydrogenase
The levels of substrates and products
Products from where, also feed into the Krebs cycle?
Products from the breakdown of amino acids and fatty acids
Give an example of a poison that affects the Krebs cycle?
Sodium fluroacetate
How does sodium fluoroacetate result in poisoning?
Inhibits aconitatase citrate—/-> isocitrate so citric acid accumulates
Give an example of a disease associated with abnormal Krebs cycle function
Beri beri, vitamin B1 (thiamine) deficiency
How does beri beri affect the Krebs cycle;e?
Thiamine pyrophosphate is needed for the PDH complex and α-ketoglutarate dehydrogenase so deficiency leads to high levels of pyruvate and α-ketoglutarate in blood
What is thiamine needed for?
PDH complex and α-ketogluatarate dehydrogenase
Symptoms of beri beri
Damage to peripheral nervous system and enlargement of the heart
