Citric acid cycle Flashcards
How does pyruvate get into the CAC?
Pyruvate gets converted to acetyl-CoA by PDC and then enters the Kreb’s Cycle.
How many reactions are there in the CAC?
8
All the reactions of glycolysis occur in the ________.
cytosol
Describe, very generally, the amphibolic nature of the CAC.
The CAC is involved in both catabolism of carbohydrates and anabolism of carbs, fats, nucleic acids, etc.
Only one _____ is made per cycle of the CAC.
GTP
NADH is cashed in at the mitochondria for how many ATP, practically?
FADH2?
- 5
1. 5
Glycolysis will not be affected if not taking in oxygen as long as what occurs?
Lactic acid fermentation continues to supply NAD+
When not undergoing an emergency, during low oxygen conditions, what will occur to glycolysis?
It will slow
What is paradoxical about the CAC and oxygen?
It cannot run without oxygen but, not a single molecule of oxygen is needed for any of the 8 reactions of this cycle or PDC.
What happens to the CAC when malonate is added?
Glycolysis goes on but oxygen consumption is stopped.
Malonate is similar to succinate but is 3C. It works with succinate DH and blocks the consumption of oxygen, stopping the cycle.
When succinate, fumerate, malate or oxaloacetate are added to the simple reaction (yeast extract with metabolites), the reaction is accelerated a lot. Why?
These aren’t just substrates, they are catalysts.
What are catalysts?
Bring two substrates together and increase the rate of reaction.
They are not used up in the reaction.
Facilitate reaction and then are regenerated.
What are the 8 enzymes of the CAC, starting from after PDC, in order?
1 - Citrate synthase 2 - Aconitase 3 - Iso-citrate DH 4 - a-ketogluterate DH 5 - Succinyl-Coenzyme A synthetase 6 - Succinate DH 7 - Fumerase 8 - Malate DH
What are the five co-factors of PDC?
NAD+, TPP, Lipoate, FAD, CoA
2 of the co-factors of the PDC reaction can be considered substrates. These are?
Why is it more correct to refer to them as co-factors?
CoA
NAD+
Still call them co-factors and not substrates because they are eventually regenerated.
Which enzyme leads to generation of GTP in the CAC?
Succinyl-coenzyme A synthetase
_________ enzymes do not require ATP; _________ enzymes require ATP for synthesis.
Synthases
Synthetases
Aconitase is similar to what enzyme type?
Isomerase
Fumerase is similar to what type of enzyme?
DH
Describe PDC. Do not describe its co-factor or enzyme components.
Multi-enzyme complex containing three enzymes associated together non-covalently.
Describe E1 of PDC.
Pyruvate dehydrogenase
- TPP cofactor bound to E1
Describe E2 of PDC
Dihydrolipoyl transcacetylase
- lipoic acid co-factor
- CoA substrate
Describe E3 of PDC
Dihydrolipoyl DH
- FAD bound
NAD+ substrate
What are the advantages of the multienzyme complex?
1 - Higher rate of reaction
2 - Minimize side reactions
3 - Coordinate control
How does the multienzyme complex accomplish a higher rate of reaction?
Because the product of one enzyme acts as the substrate of the other and is available for the active site of the next enzyme without much diffusion.
What is the possible side reaction of PDC?
After E1, 2C intermediate can come out as acetaldehyde which can be toxic.
How is the side reaction of PDC minimized by having a multi-enzyme complex?
Product of E1 is immediately taken by E2 to reduce to possibility of the side reaction.
Describe how the multi-enzyme complex affords coordinated control.
One enzyme can control the rest. Together, can be controlled very well.
What is the active part of CoA?
SH (reduced)
What is the reduced active part of CoA, oxidized?
SH - reduced
S - oxidized
In the PDC mechanism, which co-factors are immobilized, which are mobile?
FAD, TPP, lipoamide are covalently bound (immobile)
CoA and NAD+ are non-covalently bound (mobile)
What is the co-factor for E1?
TPP (ylid form)
What is the co-factor bound to E2?
Lipoamide (transiently bound to CoA)
What is the co-factor bound to E3?
FAD (Transiently bound to NAD+)
PDC is similar to what enzyme in terms of regulation?
Glycogen synthase.
inactive when phosphorylated, active when not phosphorylated
What enzyme phosphorylates PDC?
PDC kinase
How is PDC kinase activated, or more specifically, what activates it?
NADH, Acetyl CoA
What inhibits PDC kinase?
Pyruvate, ADP, Ca2+, K+, high Mg2+
What activates the PD phosphatase?
Mg2+, Ca2+