24 - Citric Acid Cycle Flashcards
The citric acid cycle’s main purpose is to oxidize _______ fuels for harvesting high energy _______.
Carbon
Electrons
The citric acid cycle is _________, meaning it undergoes catabolism and anabolism.
Amphibolic
The citric acid cycle is the source of precursors for biosynthesis and takes place inside the ________.
Mitochondria
What are other names for the citric acid cycle?
Tricarboxylic acid cycle (TCA)
Krebs cycle
The citric acid cycle is the oxidation of 2-carbon units to produce what?
2 CO2 molecules
1 GTP
High energy electrons in the form of NADH and FADH2
This is the activated form of acetate.
Acetyl CoA
Acetyl CoA can be obtained from three energy nutrients, which are…
Carbohydrates
Lipids
Proteins
To get acetyl CoA from pyruvate (glycolysis) there are 3 steps that must occur, which are…
Decarboxylation
Oxidation
Transfer acetyl group to coenzyme A (CoA)
The reactions to get acetyl CoA from pyruvate are coupled to preserve _______ to drive the formation of NADH and acetyl CoA.
Energy
Pyruvate must first enter the mitochondria, and to do this it utilizes…
Mitochondrial Pyruvate Carrier (MPC)
This enzyme catalyzes the decarboxylation of pyruvate.
Pyruvate dehydrogenase complex (PDH or PDC)
The pyruvate dehydrogenase reaction requires what?
3 enzymes
5 coenzymes
What are the 3 enzymes required for the PDH reaction?
E1
E2
E3
What are the 5 coenzymes required for the PDH reaction?
Catalytic cofactors – Thiamine pyrophosphate (TPP); Lipoic acid; FAD
Stoichiometric cofactors – CoA; NAD+
What are the reactants for the PDH reaction?
Pyruvate; NAD+; CoA
What are the products for the PDH reaction?
Acetyl CoA; Co2; NADH; H+
The PDH complex is considered (ACTIVE/INACTIVE) when it is phosphorylated, and (ACTIVE/INACTIVE) when it is dephosphorylated.
Inactive
Active
PDH is regulated by _________ interactions and reverse _________.
Allosteric
Phosphorylation
In the PDH complex, high ________ directly inhibits E2.
Acetyl CoA
In the PDH complex, products increase __________ of PDH E2, while accumulation of ADP and pyruvate activate _________.
Phosphorylation
Phosphatases (dephosphorylation)
In the PDH complex, all energy containing nutrients should be converted to…
Acetyl CoA
The citric acid cycle occurs under (ANAEROBIC/AEROBIC) conditions and produces more energy from glucose than glycolysis.
Aerobic
This is what links glycolysis to the citric acid cycle.
Pyruvate dehydrogenase (PDH)
The first step in the citric acid cycle is the condensation of 4-carbon _________ and 2-carbon acetyl group of _________.
Oxaloacetate
Acetyl CoA
Oxaloacetate reacts with acetyl CoA + _______ and yields ________ and CoA.
Water
Citrate
What is the first step (oxaloacetate to citrate) catalyzed by?
Citrate synthase
In the second step, citrate isomerize to _________. The hydroxyl group of citrate is not in the proper location for oxidative decarboxylation.
Isocitrate
In the isomerization of citrate to isocitrate, dehydration/hydration moves OH atoms via the enzyme….
Aconitase
Aconitase uses an _______-_______ cluster to bind citrate.
Iron-sulfur
This is the first of 4 oxidation-reduction reactions. It is the rate limiting step of the citric acid cycle.
Isocitrate dehydrogenase
Isocitrate is converted to __________ using ________ ________.
alpha-Ketoglutarate
Isocitrate dehydrogenase
In the conversion of isocitrate to alpha-Ketoglutarate, there is an unstable intermediate, __________, that loses CO2 while bound to the enzyme.
Oxalosuccinate
This complex is similar to the pyruvate dehydrogenase complex (PDH/PDC). It catalyzes a similar reaction.
alpha-Ketoglutarate dehydrogenase
Both PDH and alpha-Ketoglutarate dehydrogenase complex reactions decarboxylate an alpha-ketoacid and create a _________ linkage with CoA.
Thioester
The alpha-ketoglutarate dehydrogenase converts _________ to _________.
alpha-Ketoglutarate
Succinyl CoA
Succinyl CoA contains what?
High energy thioester bond
This is the only step that directly yields a high energy phospho-transfer compound (GTP, ATP).
Succinyl CoA synthetase
The succinyl CoA synthetase converts _________ to ________.
Succinyl CoA
Succinate
In tissues that perform many anabolic reactions (liver), succinyl CoA synthetase converts succinyl CoA + ________ + _______ into succinate + _________ + _________.
Phosphate (Pi); GDP
CoA; GTP
In places that perform a large amount of cellular respiration (skeletal and heart muscle), succinyl CoA synthetase converts succinyl CoA + ________ + _______ into succinate + ________ + ________.
Phosphate (Pi); ADP
CoA; ATP
Succinate dehydrogenase catalyzes the formation of ________ into ________ while generating ________.
Succinate
Fumarate
FADH2
Where is succinate dehydrogenase located?
Inner mitochondrial membrane
Succinate dehydrogenase is located in the inner mitochondrial membrane and is directly associated with the ________ _______ ________ (Complex II).
Electron transport chain
FADH2 is actually not released from the enzyme (succinate dehydrogenase), but electrons are passed directly to ______ in the electron transport chain.
Co-Q
Fumarase catalyzes the hydration of _________ to _________.
Fumarate
L-Malate
This is the final step of the citric acid cycle in which what enzyme is used?
Malate dehydrogenase
The oxidation of malate has a (POSITIVE/NEGATIVE) standard free energy.
Positive
Malate dehydrogenase recognizes specifically ________, and the reactions are driven by the use of the products which are ________ and ________.
L-Malate
Oxaloacetate
NADH
In the final step of the citric acid cycle, oxaloacetate and NADH go on to be used for what?
Oxaloacetate — Citrate synthase (repeat cycle)
NADH — electron transport chain
High ________ directly inhibits PDH complex subunit E2.
Acetyl CoA
Energy ________ of the cell dictates PDH complex activity.
Charge
Phosphatases are also stimulated by _______ which increases to initiate muscle contraction.
Calcium (Ca2+)
________ can stimulate fatty acid synthesis by activating phosphatases and increasing the conversion of pyruvate to acetyl CoA (precursor for fatty acids).
Insulin
Citrate synthesis prevents the wasteful hydrolysis of ________.
Acetyl CoA
T/F. Oxaloacetate binds to the enzyme first, then enzyme undergoes the configurational changes to accept citrate. The condensation reaction yields acetyl CoA.
False. Oxaloacetate binds to the enzyme first, then enzyme undergoes the configurational changes to accept acetyl CoA. The condensation reaction yields citrate.
The control site is isocitrate dehydrogenase. It is allosterically stimulated by _______, enhancing enzyme affinity for substrate. Reaction product, _______ also inhibits by directly displacing _______.
ADP
NADH
NAD+
This control site is alpha-ketoglutarate dehydrogenase. This complex is similar to PDH and is allosterically inhibited by its products, ________ and ________.
Succinyl CoA
NADH
Control at isocitrate dehydrogenase leads to a build up of citrate (easily converted from isocitrate) which can transport to the cytosol and signal ___________ and halt _________.
Phosphofructokinase
Glycolysis
Alpha-ketoglutarate that builds up from enzyme inhibition can be used for synthesis of _______ ______ and _______ _______.
Amino acids
Purine bases
The TCA cycle is __________, meaning it has “fill up” reactions that provide intermediates to replenish the cycle. Two major reactions are the degradation of amino acids and the carboxylation of pyruvate.
Anaplerotic
In this anaplerotic reaction, ________ carboxylation replenishes oxaloacetate.
Pyruvate
In this anaplerotic reaction, which amino acids are degraded to replenish alpha-ketoglutarate?
Gln Pro His Arg **Lead to Glutamate
In this anaplerotic reaction, which amino acids are degraded to replenish succinyl CoA?
Thr Met Ile Val **Lead to Propionyl CoA
In this anaplerotic reaction, which amino acids are degraded to replenish fumarate?
Phe
Tyr
Asp
In this anaplerotic reaction, which amino acids are degraded to replenish oxaloacetate?
Asn – leads to Asp
When energy needs are met, intermediates are drawn for biosynthesis of other molecules. They are replenished by formation of oxaloacetate from ________.
Pyruvate
The citric acid cycle oxidizes _____ carbon units.
2
PDH (or PDC) is regulated both _________ and by _________.
Allosterically
Phosphorylation
The citric acid cycle is a source of _________ precursors.
Biosynthetic
Anaplerotic reactions are required during states of low ________.
Energy
