CAC- PDC Flashcards
What is the CAC?
A series of eight reactions, oxidising the acetyl groups of acetyl CoA to two CO2, converting the liberated free energy into the reduced compounds NADH and FADH2.
What does one complete cycle of CAC yield?
Two CO2, Three NADH, one FADH2 and one GTP.
What is the reaction pathway of CAC?
3 NAD+ + FAD + GDP + Pi + Acetyl CoA —-> 3NADH+ FADH2 + GTP + CoA + 2 CO2
What happens to the oxaloacetate used in the first step?
It is regenerated in the last one, thus can oxidise unlimited number of acetyl gruop.
Where are all CAC enzymes found?
In the mitochondria.
What is required of acetyl group oxidation to the two CO2?
Transfer of four electron pairs, accounted for by reduction of 3 NAD+ to 3 NADH and reduciton of FAD to FADH2.
Where is the free energy from acetyl group oxidation conserved?
NADH and FADH2
What is the end-product of anaerobic and aerobic glycolysis?
Anaerobic is lactate, whilst pyruvate is aerobic.
Multienzyme Complexes
Protein complexes where two or more sequential steps are catalysed.
Why are enzymatic reaction rates increased in multienzyme complexes?
Usually enzyme reaction rates ae limited by frequency in which enzymes collide with their substrates, in ME , the distance the sequential steps occur is reduced, limining need for chance collision.
How do ME complexes minimise side reactions?
Reduced distance between enzymes reduces chance for metabolic intermediates produced reaction with other molecules.
Pyruvate Dehydrogenase Complex
Forms acetyl-CoA from pyruvate through oxidative carboxylation
Oxidative Decarboxylation
A reaction where a carboxylate group is removed, forming CO2.
What are the three enzymes in the PDC?
Pyruvate Dehydrogenase, Dihydrolipoyl Transacetylase and Dihydrolipoyl dehydrogenase.
Stoichiometry of PDC?
Pyruvate + CoA + NAD+ —-> acetyl-CoA + CO2 + NADH
What are the 5 coenzymes the PDC requires?
Thiamine Pyrophosphate, Lipoic Acid, Coenzyme A, FAD and NAD+
Thiamine Pyrophosphate
Decarboxylates pyruvate, yielding a hydroxyethyl TPP carbanion
Lipoic Acid
This accepts the TPP formed hydroxyethyl carbanion as an acetyl group.
What is the first step in PDC?
E1, utilising TPP, decarboxylates pyruvate with forming of hydroxyethyl-TPP intermediate.
What is the second PDC step?
Hydroxyetyl formed from E1 transfers to E2, which attacks lipoamide disulfide, eliminating TPP, thus HE oxidised to an acetyl group as LAD is reduced.
What does the lipoamide group consist of?
Lipoic acid, linked via amide bonds to the amino group of a lysine residue.
Structure of Lipoamide
Has a reactive center, being a cylci disulfide that can be reversible reduced to yield dihydrolipoamide
What is the third step in the PDC?
E2 catalyses transesterfication, where acetyl is transferred to CoA, yielding acetyl-CoA and dihydrolipoamide-E2.
What is the fourth step in PDC?
E3 reoxidises dihydrolipoamide to regenerate the lipoamide group, completing the cycle.
What is step 5 of PDC?
The reduced E3 sulfhydryl groups are reoxidesd through FAD funelling electrons to NAD+, yielding NADH.
How does the PDC channel molecules between its enzymes?
A lipoyllysyl arm that swings disulfide group from E2, ‘picking up’ hydroxyethyl group to the E2 active site, where HE forms acetyl, then transferred to E3 where reduced disulfide is reoxidised.
Why are lipoamide containing enzymes like PDC susceptible to arsenic poisoning?
It contains two sulfur, of which arsenic binds, removing its hydrogens, halting cellular respiration.
Lipoamide structure.
A hexagon with the left two bonds removd, a H-S replacing C1, an R group at C4 and H-S replacing C5.
