TCA cycle Flashcards
Where does glycolysis, pyruvate processing, TCA cycle and ETC happen?
glycolysis: cytoplasm
pyruvate processing & TCA cycle: mitochondrial matrix ETC: inner membrane
What is cristae?
extensions of inner membrane
layers of sac like structures.
fill inside of mitochondria.
are connected to inner membrane by short tube
under hypoxic or anaerobic, what happens to pyruvate?
fermentation into ethanol or lactate
under aerobic conditions, what happens to pyruvate?
pyruvate –> acetyl-Coa –> produces CO2 and water
5 coenzymes required for pyruvate processing?
TPP
Lipoyl lisine (lipoamide)
FAD
NAD+
CoA-SH
Pyruvate processing catalyzed by which enzyme?
Pyruvate dehydrogenase complexe
Which 3 enzymes for pyruvate processing?
Pyruvate dehydrogenase
Dihydrolipoyl transacetylase
Dihydrolipoyl dehydrogenase
Pyruvate processing regulated by what?
Feedback inhibition: if products of glycolysis or pyruvate are abundant –> PDH is phosphorylated and inhibited through change in conformation
5 steps of pyruvate processing
- decarboxylation of pyruvate to aldehyde
- oxidation of aldehyde into carboxylic acid –> electrons reduce lipoamide to form thioester
- formation of acetyl-coA
- Reoxidation of lipoamide cofactor
- Regeneration of oxidized FAD cofactor –> forms NADH
FAD with which enzyme?
Dihydrolipoyl dehydrogenase
TPP with which enzyme?
Pyruvate dehydrogenase
Lipoyl lysine with which enzyme?
Dihydrolipoyl transacetylase
NAD and CoA-SH in which steps of pyruvate processing?
NAD in step 5 + CoA-SH in step 3
Does coenzyme A stay on enzyme’s structure?
No. associate, fulfill function, dissociate
Function of Coenzyme-A?
accept and carry acetyl groups –> carries remaining carbons from glucose to TCA cycle to be further oxidized
Multiple intermediates from CAC can be used as reactants in other metabolic pathways –> name?
Anaplerotic reactions
CAC = amphibolic?
Involves both catabolism and anabolism
Why anaplerotic reactions?
To replenish depleted cycle intermediates
4 enzymes for anaplerotic reactions
pyruvate carboxylase
PEP carboxykinase (CO2 and GDP)
PEP carboxylase (HCO3-)
malic enzyme (pyruvate + HCO3- + NAD(P)H)
first substrate of TCA cycle? how many carbons?
Acetyl-CoA –> 2C
Rate limiting step of CAC cycle?
Step 1: citrate synthesis
What does step 1 of TCA largely depend on?
Oxaloacetate concentration
acetyl-CoA + oxaloacetate –> citrate
Step 1. Citrate synthase. F + I
citrate –> isocitrate (passing through what?) + rationale?
passing through cis-aconitate. Step 2. Aconitase. U + R. secondary alcohol is a better substrate for oxidation
Isocitrate –> alpha-ketoglutarate
Step 3. isocitrate dehydrogenase. decarboxylation. produces NADH and CO2. F + I
alpha-ketoglutarate –> succinyl-CoA
Step 4. Alpha-ketoglutarate dehydrogenase. F + I. produces NADH and CO2
Succinyl-CoA –> Succinate
Step 5. Substrate level phosphorylation. Succinyl-CoA synthetase. produces GTP. F + R
Succinate –> fumarate
Step 6. Alkane to alkene. Succinate dehydrogenase (bound to inner membrane, act as complex II in ETC). equilibrium + R
Fumarate –> L-malate
Step 7. Fumarase. water added (OH- and H+), always trans –> intermediate of carbanion. F + R
L-malate –> oxaloacetate
Step 8. L-malate dehydrogenase. U + R. produces NADH!
Which steps of TCA produce NADH?
Steps 3, 4 and 8. (2 decarboxylation and one during regeneration of oxaloactate)
Which step of TCA produces FADH2?
Step 6. succinate to fumarate
Which enzyme is similar to the pyruvate dehydrogenase complex?
alpha-ketoglutarate complex. same enzymes and mechanism but active sites different to accommodate different sized substrate
Which molecule is has a high-energy thioester bond just like acetyl-CoA?
Succinyl-CoA
When is there a net full oxidation of all glucose carbons?
Step 4 of TCA cycle. after 2nd decarboxylation –> forming succinyl-CoA
What is formed at the end of TCA cycle?
2 CO2 + 3 NADH + FADH2 + GTP + CoA + 3 H+
What is used during the TCA cycle?
1 Acetyl-CoA + 3 NAD+ + FAD+ + GDP + Pi + 2 H2O
How many ATP produced after 1 glucose passes through TCA cycle?
21 ATP (10.5 per turn)
NADH –> 2.5 each
FADH2 –> 2 each
GTP –> 1 each
Energy of which oxidations conserved to reduce NAD+, FAD+ and GDP?
Of step 3 and 4. both decarboxylations by isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase
Which reaction is an isomerization in TCA cycle?
step 2: citrate to isocitrate catalyzed by aconitase
Which step is a condensation reaction in TCA cycle?
Step 1: Oxaloacetate + acetyl-CoA –> citrate. by citrate synthase
Which steps are oxidation reactions in TCA cycle?
Steps 3, 4, 6 and 8
Which step is a hydration reaction in TCA cycle?
Step 7. fumarate to L-malate by fumarase
Which step is a substrate level phosphorylation in TCA cycle?
Step 5. Succinyl-CoA to succinate
