Citric Acid Cycle Flashcards
The 5 cofactors (coenzymes) in PDC (Pyruvate Dehydrogenase Complex) are:
E1 - Thiamine Pyrophosphate (TPP)
E2 - Lipoic Acid
E2 - Co-A
E3 - FAD
E3 - NAD+
What types/how many nucleophilic attacks are in the PDC mechanism?
Three nucleophilic attacks, all of which are Sn2
What are the three enzymes in PDC?
E1 - Pyruvate Dehydrogenase
E2 - Dihydrolipoamide Acetyltransferase
E3 - Dihydrolipoamide Dehydrogenase
What are the advantages of multi-enzyme complexes?
- Higher rate of reaction
- Minimum Side Reaction
- Coordinated Control
Why is Arsenic so deadly?
Arsenic compounds covalently bind to Sulfhydryl compounds, thus inactivating them.
Dihydrolipoamide is a critical cofactor of the PDC mechanism and has two sulfhydryl groups. Arsenic deactivates these groups which halts the PDC mechanism.
Caused the death of Charles Darwin and Napoleon Bonaparte
Reaction 1 of the citric acid cycle
Citrate Synthase - Formation of Citroyl CoA intermediate
Reaction 2 of the CAC
Aconitase - Catalyses the isomerization reaction, creating Isocitrate
Reaction 3 of the CAC
Isocitrate Dehydrogenase - Two isoforms of this enzyme, each uses Nad+ and NADP+ as respectively as electron acceptors. Produces alpha-ketoglutarate
Reaction 4 of the CAC
Alpha-Ketoglutarate Dehydrogenase - Complex similar to Pyruvate Dehydrogenase complex, NAD+ is electron acceptor. Produces Succinyl-CoA
Reaction 5 of the CAC
Succinyl CoA Synthetase - Very exergonic, used to make GTP.
This reaction is the only one in the CAC that uses substrate-level phosphorylation. Produces Succinate
Reaction 6 of the CAC
Succinate Dehydrogenase - Oxidation of Succinate to Fumarate.
Malonate has a similar structure to Succinate and competitively inhibits the SDH reaction
Reaction 7 of the CAC
Fumarase Reaction - Hydration of Fumarate to Malate (specifically L-Malate).
(highly stereospecific enzyme, cis-fumarase is not recognized by it)
Reaction 8 of the CAC
L-Malate Dehydrogenase - Oxidation of Malate to Oxaloacetate.
It is an NAD+-dependant enzyme
Pulled in forward direction by citrate synthase reaction as oxaloacetate is depleted very quickly
NOT exergonic
How is the conservation of energy of oxidation in the CAC done?
The two carbonyl acetyl groups produced in the PDC mechanism enter the CAC.
Two molecules of CO2 are then released in the cycle
What is the central hub of the CAC?
The amphibolic nature of the CAC is its central hub.
The pathway is used for catabolic reactions to generate energy as well as anabolic reactions to generate metabolic intermediates for biosynthesis
