Lectures 7-9: Pyruvate Dehydrogenase Complex & TCA Cycle

Question 1

Name the 5 cofactors of Pyruvate Dehydrogenase Complex:

Answer 1

1. TPP (Thiamine Pyrophsophate)
   
   • transfers activated 2-carbon units
   • transfers hydroxyethyl group from pyruvate to (E2)
2. Lipoic acid:
   
   • picks up hydroxyethyl from TPP, oxidizes it to acetic acid.
3. Coenzyme A:
   
   • takes acetic acid away as acetyl CoA
4. FAD (Flavin adenine Dinucleotide)
   
   • takes electron from reduced lipoyllysine, converting it back to its oxidized form.
5. NAD+ (Nicotinamide adenine dinucleotide)
   
   • FADH2 passes a H ion to NAD+ to make NADH + H+
   • NADH takes 2 e- to ETC

Question 2

Regulation of PDC:

Answer 2

• If cell already has energy, dont run PDC.
• E1 is regulated enzyme.

-PDC is off:
enough energy; NADH, ATP, CoA inhibit process.

-PDC is on:
not enough energy; ADP and pyruvate stimulate

Question 3

TCA Regulation by step:

Answer 3

1. citrate synthase is regulated by:
   
   • substrate available (oxaloacetate)
   • product inhibition (inhibited if too much NADH, ATP, or alpha-ketoglutarate.
2. Isocitrate dehydrogenase:
   
   • substrate availability [ADP] + [NAD+]
   • product inhibition (inhibited if too much NADH, ATP)
3. Alpha-ketoglutarate:
   
   • product inhibition (too much succinyl CoA, NADH, ATP
4. Succinyl CoA synthetase:
   
   • low [product] pulls reaction forward
5. Succinate DH:
   
   • low [product] pulls reaction forward.

Question 4

Products per cycle of TCA:

Answer 4

• 3 NADH, 1 FADH2, 1 GTP, 2 CO2

Question 5

Functions of aconitase:

Answer 5

1. isomerize citrate to isocitrate
2. detector of low iron concentration:
   
   • if low [Fe], the Fe-S cluster falls apart.
   • resulting effect is increased [Fe] in cell.

Question 6

Two mRNAs that aconitase bind to:

Answer 6

1. Ferritin mRNA:
   
   • aconitase binds to IRE (iron response element) stem loop of ferritin mRNA 5’ end.
   • blocks ferritin translation and it cannot be synthesized.
   • ferritin cannot sequester Fe in cell, so more is available.
2. Tranferrin receptor (TfR) mRNA:
   
   • aconitase binds to IRE of TfR mRNA 3’ end.
   • stabilizes TfR mRNA; increasing synthesis.
   • TfR transports more Fe into cell, so more is available.