Citric Acid Cycle Flashcards
What type of pathway is the citric acid cycle?
Catabolic and anabolic
Where does the citric acid cycle occur?
In the mitochondria.
The addition of which group led to the name of acetyl CoA?
The addition of a covalently bound acetyl group making a thiol bond.
What is CoA in the acetyl coA molecules?
It is an energy carrier.
Is there a lot of energy in the acetyl CoA molecule and the attachment of which group makes it ‘activated for transfer for acetyl groups and metabolism?
High energy.
Acyl group attached to CoA = ‘activated for transfer’ for acetyl groups in metabolism.
What is acetyl coA?
It is an essential metabolite that fuels the citric acid cycle to direct end-product of fatty acid and amino acid catabolism.
How is pyruvate able to enter the mitochondria to participate in the citric acid cycle?
In the presence of O2 via Mitochondrial Pyruvate Carrier Protein.
Which enzyme is used to convert pyruvate to Acetyl-CoA?
Pyruvate dehydrogenase.
PDH
What is the pyruvate dehydrogenase enzyme doing to pyruvate to catalyse it to become acetyl CoA?
oxidising and decarboxylating it
Occurs in the mm of eukaryotes.
How many copies of enzyme subunits are needed for the conversion of pyruvate to acetyl coA?
multiple copies of 3 enzyme subunits.
E1, E2, E3
Can PDH be seen using an electron microscope?
Yes
Describe the regulation of converting pyruvate to acetyl coA?
- strong regulation
- allosteric
- covalent phosphorylation
When is PDH off?
When there is ample fuel available and when cell’s energy is low.
Mutations in PDH genes or thiamine.
What is an essential enzyme cofactor associated with the regulation of PDH?
Thiamine.
What happens when pyruvate cannot be converted?
Energy dysfunction = brain damage ex:thiamine deficiency.
What did Hans Krebs discover?
That certain organic acid anions stimulated pyruvate oxidaton.
What were the organic acid anions what Krebs discovered that stimulated pyruvate oxidation?
- Dicarboxylic acids COO- x2
2. TRicarboxylic acids COO- x3
What is the start/end product of the Krebs cycle?
4C Oxaloacetate.
What does the first 1-3 steps of the citric acid cycle involve?
4C oxaloacetate + 2C acetyl group of acetyl coA condense to form 6C citrate.
= 3 x COO- tricarboxylic acid.
what does the 3- end of the citric acid cycle involve?
6C citrate (high energy reduced biomolecule) = oxidised and decarboxylated back to 4C oxaloacetate loses Hs with its electrons which collect on 3NADH and 1NADH2
What is the production of a full citric acid cycle for one acetyl CoA condensation with oxaloacetate?
3 NADH
1 FADH
1 GTP
2 CO2
How is acetyl group fed into the citric acid cycle?
Through combination with oxaloacetate.
What is the waste product of the citric acid cycle?
2 carbons.
Is the energy of oxidation conserved?
Yes it is so far for 1 acetyl CoA input/
What is the most common type of enzyme used in the citric acid cycle?
Dehydrogenase
Describe the claisen condensation?
This is where acetyl coA condenses with oxaloacetate (4C) to form (6C) citrate through the enzyme citrate synthase.
High energy nature citrate
Strong oxidation potential
What is the sentence to remember the enzymes in
Our City Is Kept Safe From Mobsters
Is the energy in the citric acid cycle conserved?
Yes, 3 NADH, 1 FADH, 1 GTP
What can happen to the anabolic/biosynthetic pathways of the citric acid cycle?
These intermediates can be ‘siphoned off’
What are oxaloacetate and alpha ketoglutarate produced from?
Amino acid catabolism of aspartate and glutamate.
What do anaerobic bacteria use the citric acid cycle for?
They have many enzymes/intermediates. Used for biosythesis.
What does the anaerobic bacteria citric acid cycle lack?
Lacks alpha-ketogluterate - so they do not have a functioning catabolic cycle.
Anaerobic bacteria use the citric acid cycle for biosynthesis, what does this indicate?
That the pathway evolved from an anabolic to both an anabolic and catabolic pathway when O2 became available.
Which metabolites of the citric acid cycle can alter the response of both the innate and adaptive immune response?
Acetyl CoA, succinate and fumarate.
In tumour formation what builds up?
Succinate dehydrogenase is inhibited = succinate build up. Tumour can progress more - cancer cells proliferate.
Why is it important to have synthetic precursors - to have a synthetic system?
When T cells are proliferating to activate certain responses.
What can build up of succinate and fumarate do?
these are oncometabolites that can promote tumorigenesis.
What can succinate do when it leaves the mitochondria?
It can degrade to acetyl coA and oxaloacetate where acetyl coA can acetylate histones/regulate gene expression
What are the 3 exergonic irreversible enzymes involved in the regulation of the cirtic acid cycle?
Citrate synthase
Isocitrate dehydrogenase
Alpha-ketoglutarate dehydrogenase
Regulation of pyruvate dehydrogenase is also imortant
How are the 3 exergonic irreversible enzymes of the citric acid cycle regulated?
Allosterically by
- energy indicators (high energy NADH, ATP at high conc the enzymes turn off and vice versa)
- product accumulation
- substrate availability
Why is the citric acid cycle known as the ‘hub’ of metabolism?
Because it is amphibolic (both catabolism and anabolism)
