Citric Acid Cycle Flashcards
What is the TCA cycle?
Oxidizes carbon fuels for harvesting high energy electrons, amphibolic, and occurs inside mitochondria
Broad overview of TCA?
Step 1: degradation of energy nutrients
Step 2: Acetyl CoA pool
Step 3: Acetyl CoA entry into TCA
1 NADH= ___ ATP
2.5
1 FADH= ____ ATP
1.5
1 GTP=____ATP
1
Where can Acetyl CoA be obtained from?
Carbs, Lipids, and Proteins
What 3 steps occur to get Acetyl CoA from pyruvate?
Decarboxylation
Oxidation
Transfer acetyl group to CoA also get NADH in the process
How does pyruvate enter the mitochondria and what happens to it?
Through mitochondrial pyruvate carrier and from there PDC catalyzes the decarboxylation of pyruvate
What is requried for pyruvate dehydrogenase reaction?
Three Enzymes: E1,E2, E3
5 Coenzymes: TPP, Lipoic acid, FAD, CoA, NAD+
What regulates Pyruvate dehydrogenase?
Allosteric interactions and reverse phosphorylation
High Acetlyl CoA also directly inhibits E2 and ADP and pyruvate activate phosphatases to activate PDC
How does the citric acid cycle occur?
Under aerobic conditions in the mitochondria and makes more energy from glucose than glycolysis
What is the first step of Krebbs?
Oxaloacetate reacts with acetyl CoA and water to give citrate and CoA. It is catalyzed by citrate synthase
What occurs after Citrate is formed?
(2) Citrate is converted to isocitrate by Aconitase which uses an iron sulfur cluster to bind citrate
What occurs after Isocitrate is formed?
(3) Isocitrate is converted to a-ketogluterate by Isocitrate dehydrogenase This is the RLS*** also prodduces NADH
What is the RLS of Krebbs?
Isocitrate to a-ketogluterate by Isocitrate dehydrogenase
It is the first of four redox reactions to occur (produces NADH)
What occurs after a-ketogluterate is formed?
(4)a-ketoglutarate is converted to succinyl CoA by the a-ketoglutarate dehydrogenase complex and generates NADH
What is significant about succinyl CoA?
It has a high energy thioester bond when it is hydrolyzed it directly yields a high energy phospho transfer compound such as GTP or ATP
What occurs after Succinyl CoA is formed?
(5) Succinly CoA is converted to Succinate via Succinyl CoA synthetase and yields GTP(in liver) (ATP in heart and skeletal mm)
What occurs after Succinate is formed?
(6) Succinate is converted to Fumarate via succinate dehydrogenase it yields FADH2
What occurs after Fumarate is formed?
(7) Fumarate is converted to L-Malate via Fumarase
What is significant about succinate dehydrogenase?
It is located in the inner mitochondrial membrane and directly associated with ETC complex II.
What occurs after Malate is formed?
(8) Malate is converted to OAA via Malate Dehydrogenase which produces NADH
What is the significance of malate dehydrogenase?
It is the final step and oxidation of malate has positive standard free energy and reactions are driven by use of products OAA-citrate synthase and NADH-ETC
What inhibits PDH complex E3?
NADH (high energy charge inhibits, and low energy charge stimulates)
In TCA what can stimulate phosphatases to activate PDH?
Calcium, insulin(stimulates fatty acid synthesis for pyruvate to Acetyl CoA),
Calcium, Mg, ADP, NAD, CoA, Pyruvate, and Insuline ____ PDC activity.
Activate
Acetyl CoA,NADH, ATP, Arsenite ____ PDC activity.
Inhibit
What prevents wasteful hydrolysis of acetly CoA?
Citrate Synthase, 1st control site
What is the second control site in TCA?
Isocitrate dehydrogenase, it is allosterically stimulated by ADP enhancing the enzyme affinity for substrate and produces NADH which inhibits by displacing NAD+
Thrid control site in TCA?
A-ketoglutarate dehydrogenase, Allosterically inhibited by its products succinyl CoA and NADH
How can the three checkpoints regualte other metabolic pathways?
Control at Isocit. dehydro. can lead to build up of citrate which inhibits PFK and stops glycolysis
a-ketoglut. that build up from enzyme inhibition can be used for synthesis of amino acids and purine bases
How many carbon units are oxidized in TCA?
2
