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33 Cards in this Set
- Front
- Back
- 3rd side (hint)
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Step 0 (precursor) of TCA Cycle?
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Pyruvate + Pyruvate Dehydrogenase Complex (PDC) + NAD + CoASH ----> Acetyl-CoA + NADH + CO2 + H+.
Reversible? |
Irreversible under physiologic conditions; deltaG' = -8kCal/mol.
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Describe regulation of the pyruvate dehydrogenase complex (PDC).
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Feedback Inhibition: NADH and Acetyl-CoA.
Phosphorylation inactivates PDC; de-phosphorylation activates. Mechanism of phosphorylation? |
-Phosphorylation is performed by a kinase which resides within the complex and is activated by NADH & Acetyl-CoA, and deactivated by the PDC reactants and ADP.
-De-phosphorylation is performed by a phosphoprotein phosphatase, which also resides in the complex and is activated by increasing [Ca2+] and [Mg2+]. |
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Role of [Ca2+] in the TCA cycle?
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Calcium upregulates the PDC's conversion of pyruvate to Acetyl-CoA. Where is this mechanism important?
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It plays an important role in skeletal muscle, where the release of Ca2+ during contraction should activate the phosphatase stimulating the oxidation of pyruvate and hence energy production.
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Epinephrine's role in regulation of the PDC?
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Epi, as well as other catecholamines, activate the PDC in cardiac muscle, which stimulates energy production for pumping the heart. It does so by increasing [Ca2+] (via the alpha-adrenergic receptor?)
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Where does the TCA cycle take place?
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In the mitochondrion; one of the pathway's enzymes is embedded in the inner-membrane and also participates in the electron transport chain as Complex II.
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Scorecard for the TCA cycle (per 1 molecule of Acetyl-CoA)?
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Produced: 3xNADH, 3xH+, 1xFADH2, 1xGTP, 2xCO2, 1xCoA.
Consumed: 2xH20, 1xAcetyl-CoA. |
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Mnemonic for the TCA reaction intermediates?
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Our City Is Kept Safe and Sound From Malice
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Oxalacetate
Citrate Isocitrate alpha-Ketoglutarate Succinyl-coA Succinate Fumarate Malate |
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Mnemonic for TCA cycle enzymes?
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CAIK Sounds So Fucking Mint.
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Citrate synthase
Aconitase Iso-citrate dehydrogenase alpha-Ketoglutarate dehydrogenase Succinyl-coA synthetase Succinate dehydrogenase Fumarase Malate dehydrogenase |
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Score card for the TCA cycle (per 1 molecule of glucose)?
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Produced: 6xNADH, 6xH+, 2xFADH2, 2xGTP, 4xCO2, 2xCoA.
Consumed: 4xH20, 2xAcetyl-CoA. |
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What are anaplerotic reactions?
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Anaplerotic reactions replenish 4- and 5-carbon TCA cycle intermediates to replace ones that have been shunted into side reaction pathways.
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Which steps of TCA cycle produce NADH?
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Step 3: Isocitrate ----> a-Ketoglutarate
Step 4: a-Ketoglutarate ----> Succinyl-CoA Step 8: Malate ----> Oxaloacetate |
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Which step of TCA cycle produces GTP?
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Step 5: Succinyl-CoA ----> Succinate
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Which step of TCA cycle produces FADH2?
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Step 6: Succinate ----> Fumarate
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Step 1 of TCA cycle?
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Oxaloacetate + Acetyl-CoA + Citrate Synthase ----> Citrate + CoASH
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Step 2 of TCA cycle?
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Citrate + Aconitase ----> Isocitrate
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Step 3 of TCA cycle?
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Isocitrate + Isocitrate Dehydrogenase + NAD ----> a-Ketoglutarate + NADH + CO2 + H+
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Step 4 of TCA cycle?
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a-Ketoglutarate + NAD + CoASH + a-Ketoglutarate Dehydrogenase ----> Succinyl CoA + NADH + CO2 + H+
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Step 5 of TCA cycle?
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Succinyl-CoA + GDP + Pi + Succinyl-CoA synthetase ----> Succinate + GTP + CoASH
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Step 6 of TCA cycle?
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Succinate + FAD + Succinate Dehydrogenase ----> Fumarate + FADH2
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Step 7 of TCA cycle?
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Fumarate + Fumarase ----> Malate
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Step 8 of TCA cycle?
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Malate + NAD + Malate Dehydrogenase ----> Oxaloacetate + NADH + H+
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Three enzyme cofactors of the PDC?
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1) Thiamine Pyrophosphate (TPP) - E1
2) Lipoate - E2 3) FAD - E3 |
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3 main regulatory mechanisms of TCA cycle?
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1) substrate availability (intermediates used in other pathways)
2) Feedback Inhibition 3) Allosteric regulators (e.g. Ca2+) |
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Regulation of TCA Step 3?
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ATP inhibits; ADP activates.
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Regulation of TCA Step 4?
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-Feedback Inhibition of GTP, succinyl-CoA, and NADH;
-Calcium activates (epinephrine pathway!) |
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Each turn of the TCA cycle results in how many ATP's produced?
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12 ATP (ideal); it's lower in reality for several reasons (see side 3)
-GTP produced in step 5 counts toward ATP total! |
-Each NADH creates 3xATP.
-Each FADH2 creates 2xATP. -Substrate-level phosphorylation produces 1xATP |
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What's the ideal ATP yield for one molecule of Glucose?
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38 ATP.
What steps contribute, and how much? |
Hexokinase = -1
PFK-1 = -1 G3P --> 1,3BPG = +6 1,3-BPG --> 3PG = +2 PEP --> Pyruvate = +2 Pyruvate --> Acetyl-CoA = +6 Isocitrate --> a-Ketoglutarate = +6 a-Ketoglutarate --> Succinyl-CoA = +6 Succinyl-CoA --> Succinate = +2 Succinate --> Fumarate = +4 Malate --> Oxaloacetate = +6 |
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What B Vitamin is a component of FAD?
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Riboflavin.
Where is FAD involved in the TCA cycle? |
It's a cofactor of the PDC, a-Ketoglutarate Dehydrogenase complex, and Succinate Dehydrogenase.
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What B Vitamin is a component of NAD?
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Niacin
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What B Vitamin is a component of CoA?
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Pantothenic Acid
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What B Vitamin is a cofactor of many carboxylation reactions?
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Biotin.
Example of such reactions? |
Pyruvate Carboxylase - generates Oxaloacetate from Pyruvate for use in both TCA cycle and Gluconeogenesis.
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What B Vitamin is a coenzyme in the PDC and a-KG Dehydrogenase complex?
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Thiamine (Vitamin B1) - in the form of Thiamine pyrophosphate.
Diseases caused by B1 deficiency? |
Wernicke-Korsakoff and beri-beri; both seen often in alcoholics that get their nutrition from booze instead of food.
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In the ETS, what molecules can hold either 1 or 2 electrons and transfer them one at a time?
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Flavoproteins (FAD or FMN) and Coenzyme Q.
Why is this important? |
NADH and FADH2 can ONLY transfer 2 electrons at a time, whereas the iron-sulfur complexes in Complex I and cytochromes of complex III can only accept them one at a time.
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