PDC Flashcards
Under anaerobic conditions, 2 pyruvate are ______.
NADH is _______, why?
2 pyruvate reduced to 2 lactate
NADH is oxidized to NAD+ for regeneration for step 6 of glycolysis
Under aerobic conditions, 2 pyruvate______
2 pyruvate will enter the mitochondria and pyruvate dehydrogenase complex will oxidize to 2 acetyl CoA
Also lose CO2 and produce 2 NADH in the process
Where is PDC located?
mitochondrial matrix
Major components of PDC?
E1, E2, E3
Type of reaction PDC catalyzes
Oxidative decarboxylation
Oxidation reduction
NAD+ –> NADH
Loss of CO2
Products of PDC catalyzed reaction per 1 glucose
2 Acetyl CoA
2 CO2
2 NADH
Requirements for PDC reaction
Vitamin coenzymes
Vitamin coenzymes (2)
- Catalytic, covalently bound to respective components
2. Stoichiometric, not bound, come on and off complex
Catalytic vitamin coenzymes
- Thiamin pyrophosphate (TPP)
- Lipoic acid
- Flavin adenine dinucleotide (FAD/FADH2)
Stoichiometric, not bound vitamin coenzymes
- CoA
- NAD+
Why are they called coenzymes?
Need to undergo the same type of regeneration of conformation following the reaction that an enzyme does
Is the PDC reaction reversible or irreversible?
Irreversible
3 Step Overview of PDC Reaction
- Decarboxylation
- Oxidation
- Transfer to CoA
- Decarboxylation
Pyruvate lose a CO2
Results in carbonyl group with a negative charge (acetyl group)
- Oxidation
Lose 2 e- which are transferred to NAD+ –> NADH
Results in a carbonyl group with a positive charge (acetyl group)
- Transfer to CoA
Acetyl group is transferred to CoA to yield acetyl CoA
When you add acetyl group to CoA –> form a HIGH ENERGY THIOESTER BOND
Where does decarboxylation happen?
On E1 which has TPP bound to it
Goal of oxidation and transfer (2nd step)
Transfer the acetyl intermediate that is bound to TPP to E2, specifically the lipoamide
The 2 C orginating from pyruvate are now on E2 lipoamide
THIOESTER BOND IS FORMED
origin of the lipoamide
E2 has lipoic acid coenzyme. When you attach the lipoic acid covalently to E2, it is bound to the lysine side chain –> form the lipoamide arm
Significance of lipoamide on E2
Has an S-S bond
Makes a swinging arm that can go back and forth between E1 and E2 and E2 and E3 to “shuttle the 2 carbons”
Transfer of 2C from E1 to E2 lipoamide arm is catalyzed by
E1 complex
How does the transfer of acetyl group to CoA happen?
Significance?
Lipoamide arm swings over to CoA and transfer the acetyl group
Now, the thioester bond is on the Acetyl CoA molecule –> to be used in TCA cycle
What is the transfer of acetyl group to CoA catalyzed by?
E2
Oxidation of dihydrolipoamide purpose?
Resetting PDC to allow for another catalytic cycle
How does oxidation of dihydrolipoamide happen?
- E2 with lipoamide arm swings over to E3 which has FAD covalently bound –> FAD accepts electrons and becomes reduced to FADH2 –> S-S bond is formed again on the lipoamide arm so it is ready for another round
- Then, NAD+ (which comes on and off complex) accepts the electrons from FADH2 to yield NADH and FAD regenerated
Catalyzed by E3
Allosteric regulation of PDC
PDC less active when high energy charge
- ATP negative modifier
- Acetyl CoA and NADH feedback inhibit
PDC more active when low energy charge
- ADP positive modifier
- NAD+ and pyruvate concentrations too
Hormonal regulation of PDC
Fasted state
Glucagon signaling predominates…..
Triggers phosphorylation by pyruvate dehydrogenase kinase –> inactivation of PDC
Pyruvate dehydrogenase kinase regulation
Allosterically activated by NADH and Acetyl CoA as they are simultaneously feedback inhibiting PDC allosterically
Pyruvate and ADP allosterically inhibit
Hormonal Regulation of PDC
Fed state
Insulin signaling predominates…..
PDC is dephosphorylated by phosphatase to activate
Significance of PDC reaction
To generate a high energy thioester bond in acetyl CoA that can be used in TCA cycle
All intermediates in PDC reaction are
Importance?
Covalently bound in some way to PDC throughout the entire reaction
Allows for efficiency- don’t have to wait for diffusion
Insulin signaling in fed state always results in:
Dephosphorylation of enzymes in energy transducing or bio synthetic pathways
PDK-1, PDC, pyruvate kinase are all regulated by:
Trend?
Energy charge
Activity is decreased when ATP levels are elevated because ATP is a negative allosteric modifier of all of them
