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Define amphibolic
Anabolism + Catabolism
Define catapleurotic reaction
CAC intermediates are depleted
Define anapleurotic pathways
CAC intermediates are replenished
Then, how can the CAC be described?
As an amphibolic process
1st cataplerotic reaction of the CAC
PEP formation from oxaloacetate using PEPCK
2nd cataplerotic reaction of the CAC
Oxalo. + A-CoA from citrate using ATP-citrate lyase
3rd catapleurotic of the CAC
AAs from ketoglutarate using glutamate dehydrogenase
Sole anaplerotic reaction of the CAC
Oxaloacetate from pyruvat using pyruvate carboxylase
1st amphiplerotic reaction of CAC
Malic enzyme: pyruvate → malate → pyruvate
2nd amphiplerotic reaction of CAC
Transamination between glutamate and ketoglutarate
3rd amphiplerotic reaction of CAC
Transamination between alanine and aspartate
What dictates which molecule will be transaminated?
The cell’s needs in AAs
What is a transamination pair?
Keto acid and amino acid formed once the amino group is moved
What are the 3 sections of the mitochondrion?
Inner membrane (proton gradient)
Matrix
Outer membrane (porous)
How does pyruvate get inside the matrix?
With MPCs and VDAC or mitochondrial pyruvate channels and a voltage-dependent anion channel
How’s the structure of MPCs?
MPC1 and MPC2 homodimer
How does cytosolic NADH get inside the mitochondrion?
With 2 types of shuttles
1st type of shuttle
DHAP/G3P shuttle
Steps of the DHAP/3GP shuttle
DHAP reduction into G3P
G3P goes through the outer membrane
Reoxidation of G3P + Reduction of FAD
Transfer of FADH2 electrons to coQ
2nd type of shuttle
Malate/aspartate shuttle
Steps of the malate/aspartate shuttle
Reduction of oxaloacetate to malate
Malate transport into matrix
Reoxidation of malate
Oxidation of NADH → NAD+ by complex I
Transamination of oxaloacetate into Asp
Reconversion of Asp into oxaloacetate
How is ADP+Pi brought into the mitochondrion?
ATP-ADP translocator (antiport)
Phosphate carrier (symport)
Where does ox. phos. take place?
Outer membrane
Principle of ox. phos.
Deliver electrons from NADH and FADH2
Order of electron transfer
C1 → CoQ → C3 → Cyt c →C4 → C5
What else do the complexes 1,3 and 4 do other than é transport?
Generating an electrochemical gradient from pump protons
How many H+ come from NADH?
10
How many H+ come from FADH2?
6
What is the proton gradient used by?
Complex 5 or ATP synthase (ADP+Pi → ATP)
In what order are the electrons transported?
From low to high potential molecules (weak to strong hold on electron)
What happens to complexes 1, 3 and 4 when they pump protons?
Conformational changes
Why are all the ox. phos. reactions favourable?
Really negative delta G (exergonic)
In what other way can CoQ be reduced?
Beta-oxidation of fatty acids
G3P dehydrogenase
If all the steps are extremely favourable, why are there so many redox reactions? (why not one big reaction??)
Not to waste energy along the way