Citric Acid Cycle Flashcards
The CAC is a circular pathway of ____ reactions that oxidize acetyl-CoA to carbon dioxide.
8
Where does the CAC take place?
The mitochondrial matrix
What are the 8 intermediates of the CAC (excluding acetyl-CoA)?
- Citrate
- Isocitrate
- Alpha-ketoglutarate
- Succinyl-CoA
- Succinate
- Fumarate
- Malate
- Oxaloacetate
What are the 8 enzymes of the CAC?
- Citrate synthetase
- Aconitase
- Isocitrate dehydrogenase
- Alpha-ketoglutarate dehydrogenase
- Succinyl-CoA synthetase
- Succinate dehydrogenase
- Fumarase
- Malate dehydrogenase
What is the structure of acetyl CoA?
What is the structure of pyruvate?
What is the structure of oxaloacetate?
Citrate synthase converts ________________ and __________________ to citrate via a Claisen condensation.
Acetyl-CoA
Oxaloacetate
Citrate synthase produces citrate and expels ______________.
CoASH
What is the mechanism of citrate synthase?
An irreversible Claisen condensation
What is the mechanism of action of citrate sythase?
- Acidic proton deprotonates and carbanion forms on acetyl-CoA
- Carbanion attacks C carbonyl and O protonates
- Water attacks chiral C and expels CoASH
- Citrate forms
Aconitase converts cistrate to isocitrate via an ___________________ and dehydration.
Isomerization
What is the structure of isocitrate?
The enzyme aconitase catalyzes the reversible transformation of citrate to isocitrate through the intermediary formation of the tricarboxylic acid ______________________, which normally does not dissociate from the active site.
Cis-aconitase
Aconitase contains an _________________________, which acts both in the binding of the substrate in the active site and in the catalytic addition and removal of water.
Iron-sulfur center
What is the mechanism of action for aconitase?
- Proton abstraction
- Formation of alkene
- Expulsion of hydroxyl
- Formation of cis-aconitase
- Water is added across alkene
- Formation of isocitrate
The iron-sulfur cluster of aconitase assists in what part of the enzyme’s mechanism?
The removal of water
The iron-sulfur cluster of aconitase contains a __________ residue that coordinates four iron artoms and four sulfur atoms.
Cysteine
Citrate synthase incorporates acetyl-CoA only into the pro-__ carboxymethyl group and that aconitase abstracts a proton only from the pro-__ carboxymethyl group of citrate.
pro-S
pro-R
Isocitrate dehydrogenase catalyzes the formation of alpha-ketoglutarate from isocitrate via an ________________ _________________.
Oxidative decarboxylation
Isocitrate dehydrogenase catalyzes an oxidative decarboxylation of a beta-keto acid just as ____________________ _________________ in the pentose phosphate pathway.
6-phosphogluconate dehydrogenase
What is the structure of alpha-ketoglutarate?
What is the mechanism of action for isocitrate dehydrogenase?
- Isocitrate binds enzyme and is oxidized via hydride transfer to NAD+ or NADP+
- Interaction of the carbonyl O with a bound Mg2+ or Mn2+ increases electron-withdrawing capacity of carbonyl group and facilitates decarboxylation
- Rearrangement of enol intermediate generates alpha-ketoglutarate
What is the structure of succinyl-CoA?
alpha-ketoglutarate dehydrogenase catalyzes the oxidative decarboxylation of an ____-keto acid.
Alpha keto acid
Alpha-ketoglutarate dehydrogenase cataylzes the conversion of __________________________ to _______________________.
Alpha-ketoglutarate
Succinyl-CoA
What is the mechanism of action for alpha-ketoglutarate dehydrogenase?
- TPP carbanion attacks alpha keto group
- Gamma O kicks back, expels carbon dioxide, and forms carbanionic intermediate
3.
Citrate synthase incorporates acetyl-coenzyme A only into the pro-___ carboxymethyl group and aconitase abstracts a protron from only the pro-___ carboxymethyl group of citrate.
Pro-S
Pro-R
What coenzymes are required for alpha-ketoglutarate dehydrogenase to function?
TPP
Lipoic acid
CoASH
FAD
NAD+
___________________ refers to an enzyme that catalyzes a condensation reaction that involves a nucleotide triphosphate while _______________ refers to an enzyme that catalyzes a condensation reaction that does not involve a nucleotide triphosphate.
Synthetase
Synthase
What cosubstrate is required for the reaction catalyzed by succinyl-CoA synthetase?
Inorganic phosphate
What amino acid residue assists in the succinyl-CoA synthetase reaction?
A deprotonated histidine
What is the function of GDP in the succinyl-CoA synthetase mechanism?
To dephosphorylate the amino acid residue and to form GTP
Succinyl-CoA synthetase catalyzes the conversion of _______________ to ______________.
Succinyl-CoA to succinate
Which enzyme in the CAC reduces FAD?
Succinate dehydrogenase
_____________________ _______________ catalyzes the conversion of succinate to fumarate.
Succinate dehydrogenase
Which enzyme in the CAC catalyzes a hydration reaction?
Fumarase
__________________ catalyzes the conversion of fumarate to malate via a hydration reaction.
Fumarase
Isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, and ___________________ dehydrogenase reduce NAD+ to NADH in the CAC.
Malate dehydrogenase
_________________ _________________ catalyzes the conversion of malatae to oxaloacetate in the CAC>
Malate dehydrogenase
___________________ ___________________ also known as Complex II of the electron transport chain; it is an integral membrane protein complex bound to the inner mitochondrial membrane that feeds electrons directly into the electron transport chain. It contains three different Fe-S clusters where electrons are passed from FADH2 to coenzuyme Q.
Succinate dehydrogenase
Malate dehydrogenase is pro-____ specific.
Pro-R
Why is the oxidation of malate to oxaloacetate spontaneous under cellular conditions despite the standard free energy change being close to 30 kJ?
Because OAA is constantly being converted to citrate; therefore, the product is very low, pushing the reaction forward despite such a positive standard free energy change
What are the three irreversible steps of the CAC?
- Citrate synthase
- Isocitrate dehydrogenase
- Alpha-ketoglutarate dehydrogenase
The CAC is controlled at the level of _________________ ____________ at three points: transport of pyruvate into the mitochondria by the mitochondrial pyruvate carrier, the pyruvate dehydrogenase complex, and citrate synthase.
Pyruvate entry
