Prep For TCA Flashcards
After pyruvate is made from glycolysis where does its go
From the cytoplasm to the matrix of the mitochondria
After pyruvate (3 carbons) is sent to the mitochondrial matrix, what happens
Pyruvate is oxidized (loses 2 electrons) and decarboxylated (loses co2)
“Oxidatively decarboxylated”
To turn into acetyl coa (2 carbons)
What is the structure of acetyl coa
The acetyl group (c=o) is linked to the sh group of co enzyme A
This bind it’s called the thioester bond
If the thioester bond of the acetyl coa is hydrolyzed is it endergonic or excergonic
What does this mean
Highly exergonic meaning it has high acetyl group transfer potential
(can transfer its acetyl group very well to other molecules)
What is the conversion of pyruvate to acetyl coa called
What enzyme catalyzes this reaction
The bridge reaction or pyruvate oxidation
Pyruvate dehydrogenase
What are the three enzymes in the pyruvate dehydrogenase complex that turn pyruvate to acetyl coa
Pyruvate dehydrogenase (E1)
Dihydrolipoyl transacetylase (E2)
Dihydrolipoyl dehydrogenase (e3)
Why are e1 e2 and e3 needed for the bridge reaction
It allows the substrates from each reaction to move from one active site of the enzyme to that next
This short distance between all the Enzymes minimized side reactions and speeds up the reaction rate because it take less time to go from one place to the other
What is the prosthetic group of E1 and what reaction does it catalyze
TPP (thymine pyrophosphate)
Oxidative decarboxylation of pyruvate
What is the prosthetic group of E2 and what reaction does it catalyze
Lipoamide
Transfer of the acetyl group to coA
What is the prosthetic group of E3 and what reaction does it catalyze
FAD
Regeneration of the oxidized form of lipoamide
How are the enzymes situated in the pyruvate dehydrogenase complex
The e2 is at the core
E1 and e3 surrounding the core
What is the linker region
The region on E2that flips back and forth from e1 and e3
What five coenzymes does the pyruvate dehydrogenase complex need
TPP, LIPOAMIDE, FAD (catalytic coenzymes)
CoA, NAD+ (stoichiometric coenzymes, act as actual substrates)
How does first step the reaction catalyzed by e1 work
The TPP cofactor of E1 is in the ylid form (+ and - charges next to each other)
Pyruvate react with the carbanion of TPP
It’s becomes decarboxylated (lose co2) and becomes hydroxyethyl TPP
How does second step the reaction catalyzed by e1 work
The previously made hydroxy ethyl TPP is oxidized to an acetyl group (c=o)
Then the acetyl group gets transferred to Lipoamide (e2) where the Lipoamide disulphide bond is reduced
The e2 swings to the active site of e1 for this to happen
What is the structure of E2 transacetylase
The enzyme has a lysine residue that’s covelently linked to Lipoamide
The Lipoamide acts as an arm that swings from e1 or e3
How does the reaction catalyzed by e2 work
The previous acetyl group that was attached to the E2 Lipoamide (acetyl Lipoamide) is transferred to CoA
The thioester bond is still intact
The Lipoamide is fully reduced (dihydrolipoamide)
After dihydrolipoamide is made from being fully reduced, how does the next reaction with E3 happen
The fully reduced dihydrolipoamide need to transfer its electrons to another molecule (become oxidized)
To turn back into Lipoamide
How does the reaction catalyzed by e3 work
The Dihydrolipoyl amide transfers electrons to FAD (cofactors of E3)
This make FADH2 (reduced) and regenerated Lipoamide (oxidized)
The electrons from fadh2 get transferred to NAD+ to make FAD and NADH
What does the NADH do after being form after the E3 step of the bridge reaction
It can move down the electron transport chain
Once acetyl CoA is made what happens
It’s either oxidzed to become co2 through the citric acid cycle
Or it’s used to build fatty acids
In animals is the conversion of pyruvate to acetyl CoA reversible
No irreversible
How is the pyruvate dehydrogenase complex regulated
Allosterically regulated
Or
Covalently modified
How is the pyruvate dehydrogenase complex allosterically regulated
The acetyl CoA binds to E2 in inhibits it from making more acetyl CoA
Or the NADH bind to E3 and inhibits it
How is the pyruvate dehydrogenase complex regulated through covalent modification
The E1 serine residue gets phosphorylated by kinase and inactivate the pyruvate dehydrogenase (entires reaction)
Or the e1 PDH gets dephosphorylated by phosphatase and is active
When the muscle is at rest ( energy change is high) how is the pyruvate dehydrogenase complex regulated
This means there is high NADH ATP AND ACETYL COA
We don’t need more atp
these three things stimulate pyruvate dehydrogenase kinase which inactivates the PDH to stop the citric acid cycle from starting
This makes it so that less atp is made from TCA
When the muscle is active ( energy change is low) how is the pyruvate dehydrogenase complex regulated
There’s more pyruvate since glycolysis is happening more to get more atp
There’s also more adp since there’s less atp
The adp and pyruvate inhibit pyruvate dehydrogenase kinase which activate PDH