Bioenergetics 4 : Citric Acid cycle Flashcards
Where does CAC take place
The matrix of the mitochondria or cytosol of bacteria
What is endosymbiosis (relating to mitochondria)
Mitochondria may have been originally bacteria that was taken up by a Eukaryotic cell.
What is the benefits of Endosymbiosis
Mitochondria permit an existence with oxygen which is toxic.
SA increasing Cristae increase the cell capacity to make ATP, allowing larger cells.
As there is more ATP, allows more complex genomes as DNA is made from ATP. Allows more complex makes diversification.
What allosterically activates PDH and what negative feedbacks it
Pyruvate, AMP, NAD, Ca2 + (signal that cells are depolarised-need ATP).
Negative feedback is AcetylcoA
Step 1 of CAC
- Citrate synthase makes Citrate from adding Acetyl CoA (2) and Oxaloacetate (4)
Step 2 of CAC
Aconitase prepares the molecule for an oxidation reaction by moving around the OH group by removing water
Step 3 of CAC
Isocitrate dehydrogenase removes CO2 which goes to the breath and the H+ are removed to make NADH
Step 4 of CAC
Alpha ketoglutarate dehydrogenase removes a CO2 and reduces an NAD+. It adds a coenzyme A group Coa-SH to a-ketoglutarate
What enzymes does Arsenic affect in the CAC and how does it work
The a-ketoglutarate dehydrogenase and pyruvate dehydrogenase are very similar
Arsenic affects both of them by binds to the lysine lipoamide which prevents it from adding an coenzyme A
Compare the structure of enzymes in PDH and aKDH
E1: PDH uses Pyruvate and aKDH uses a-ketoglutarate but both make CO2
E2: PDH and aKDH both add CoA-SH but PDH makes Acetyl-CoA whereas aKDH makes Succinyl CoA.
E3: Both reduce NAD+ to NADH + H+
Step 5 of CAC
Succinyl CoA synthetase or succinyl thiokinase. Removes the CoA, using the power of it to make an ATP or GTP -depending on the tissue. This is a substrate phosphorylation.
Step 6 of CAC
Succinate Dehydrogenase/ Complex 2 of ETC and it is the only part of the CAC that . Accepts succinate and oxidases it to fumarate. It then reduces FAD to FADH. The electrons are transferred through iron cluster and heme.
Step 7 of CAC
Fumarase adds wate to fumarate and this produces Malate.
Step 8 of CAC
Malate dehydrogenase has then oxidises Malate and reduces another NADH
How many pyruvate per glucose
2
What are the three checkpoints controlling the CAC and what inhibits or activates it
PDH, IsocitrateDH and a-ketoglutarateDH are all inhibited by ATP and NADH.
For PDH it is also inhibited by its product acetyl coA.
and For KDH it is inhibited by its product Succinyl coA -> bc it runs out of CoA
For IDH it is activated by ADP
What is the ratio of ADP/ATP that activates and inhibits IDH
Activates ADP:ATP= 10: 2
Deactivate ADP: ATP = 2:10
How does [Ca2+] in muscle regulate IDH
When there is a lot of contractions, Ca2+ goes up and there is a need for more ATP so it makes it go faster
What happens to the intermediates of CAC if one enzyme at one point is non functional?
The intermediates before the inhibition build up while the others after start to run out
Summarise the conversion of Pyruvate to acetyl coA in oxidative decarboxylation reaction
Pyruvate from glycolysis has
1. A CO2 taken off
2. A coenzyme A is added
3 A NAD+ reduced
What can be converted to acetyl CoA and what cannot be converted back
Pyruvate, fats, some amino acids. Fatty acids cannot be converted to glucose because this reaction has a high negative delta G and it is regulated. (irreversable)
What are the products of the CAC per 1 acetyl coA
2 x CO2, FADH2 and 3NADH + 1 ATP or GTP
How was CAC discovered
Hans Kreb who escaped from nazi germany during WWII. He observed that specific metabolites/intermediates increased respiration or accumulated when poisons were added. He radio labelled acetate (2Cs) that went in yet the 2CO2s that came out were different
How does the 3 enzyme parts of pyruvate dehydrogenase oxidise pyruvate
Pyruvate binds to the ThiaminePP in E1 complex leaving acetate. Acetate is then moved to lysine lipoamide on E2. Coenzyme A is joined to acetate. This reduces the lysine lipoamide and this means that the FAD in E3 will accept it. It then transfers it to the NAD to reduce it
What is the substrate level phosphorylation reaction in CAC and what does it make
Step 5 using Succinyl coA synthetase. When CoA-SH is released, the energy from this is used to add Pi to either ADP in muscle or GDP in the liver
What is the product of 1 pyruvate oxidation to acetyl coA
1 CO2, 1 NADH
What does it mean by CAC is amphibolic
Its both cata or anabolic. For anabolic reactions
- Acetyl coA-> acetylcholine
- Citrate -> fatty acids
- A-ketoglutarate-> glutamate
- Succinyl CoA-> porphyrin found in haemoglobin, cytochromes and chlorophyll
- Malate-> glucose for
- Oxaloacetate-> amino acid synthesis
What are the 4 oxidation reactions in CAC
Step 3: Isocitrate -> A-ketoglutarate
Step 4: A-ketoglutarate -> Succinyl CoA
Step 6: Succinate -> Fumarate (FADH2)
Step 8: Malate -> Oxaloacetate
What is the substrate phosphorylation reaction in CAC
Step 5 Succinyl CoA –> Succinate (removes the Coa group provides energy for substrate phosphorylation)
What is the difference between FAD and NADH
NAD+ is mobile in aqueous environment and accepts 2 electrons in a single step where as FAD which accepts single electrons is bound within enzymes and so has less reducing power.
What is a coenzyme and what is the 3 in the CAC
Complex organic structure that participates in enzymatic reactions. In CAC Co-enzyme A. NAD+ and FAD-> redox electron acceptors
