Lecture 24: TCA Cycle Flashcards
Three steps in formation of Acetyl CoA from pyruvate
Decarboxylation
Oxidation
Transfer to CoA
NADH is produced
How does pyruvate enter the mitochondria, and what decarboxylates it once inside
Mitochondrial pyruvate carrier
Pyruvate dehydrogenase complex
Pyruvate dehydrogenase requires _ enzymes and _ coenzymes- name them
3 enzymes E1, E2, E3 5 coenzymes -Thyamine pyrophosphate Lipoic acid FAD NAD CoA
Pyruvate dehydrogenase is active under which phosphorylation state
Dephosphorylated is active
What are positive/negative allosteric regulators of Pyruvate dehydrogenase kinase PDK
+ Acetyl Coa, NADH, ATP
- Pyruvate, CoA, NAD+, ADP
What are positive allosteric regulators of Pyruvate dehydrogenase phosphatase PDP
Calcium and magnesium
High levels of acetyl CoA will directly inhibit which enzyme of the pyruvate dehydrogenase complex (remember 3 enzymes and 5 coenzymes)
E2
Citrate synthase
Condensation of 4-carbon oxaloacetate and 2-carbon acetyl CoA to yield Citrate
Aconitase
Citrate –> Isocitrate
Isocitrate dehydrogenase
Isocitrate-->oxalosuccinate--> a-ketoglutarate NADH + CO2 formed Rate limiting step Activated by ADP Inhibited by ATP and NADH
a-ketoglutarate dehydrogenase complex
a-ketoglutarate–> Succinyl CoA
NADH formed
Inhibited by ATP, succinyl CoA and NADH
Succinyl CoA synthetase
Succinyl CoA–> Succinate
*GTP formed- only step yielding high energy molecule
Succinate dehydrogenase
Succinate–> Fumarate
FADH2 formed
Where is succinate dehydrogenase located, and where is FADH2 sent when formed by it
Located in the inner mitochondrial membrane directly associated with electron transport chain
FADH2 passes electrons directly to Co-Q in the ETC
Fumarase
Fumarate–> Malate
Malate dehydrogenase
Malate–> Oxaloacetate
NADH formed
Inhibited by excess oxaloacetate or NADH
How does insulin help regulate the citric acid cycle
Insulin can stimulate fatty acid synthesis by activating phosphatases and increasing conversion of pyruvate to acetyl CoA
What is the effect of Arsenite on pyruvate dehydrogenase complex
Inhibits function by binding Lipoic acid on E2
How does citrate synthase prevent wasteful hydrolysis of Acetyl CoA
Oxaloacetate must bind first, and the enzyme undergoes conformational change to accept acetyl CoA
What is the second control site in the citric acid cycle
Isocitrate dehydrogenase is activated by ADP and inhibited by NADH/ATP
What is the third control site in the citric acid cycle
a-ketoglutarate dehydrogenase
Allosterically inhibited by its products- Succinyl CoA and NADH
Also inhibited by ATP
What happens when excess citrate builds up because of the control point at isocitrate dehydrogenase, what happens to the citrate
It is transported to the cytosol and signals phosphofructokinase to halt glycolysis
What happens to a-ketoglutarate when it builds up
It can be used for synthesis of amino acids and purine bases
What are the two major anaplerotic reactions that replenish TCA cycle intermediates- and when are they important
Degradation of amino acids
Carboxylation of pyruvate
Most important during states of low energy
