TCA Cycle (Krebs Cycle)

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Questions and Answers

What is another name for the TCA cycle?

  • Kreb's Cycle (correct)
  • Electron Transport Chain
  • Calvin Cycle
  • Glycolysis

The TCA cycle occurs in the mitochondrial matrix.

True (A)

The pyruvate dehydrogenase reaction converts pyruvate to ______.

acetyl-CoA

What is the net ATP production from one turn of the TCA cycle, considering the updated values for NADH and FADH2?

<p>10 ATP</p> Signup and view all the answers

Which of the following is NOT a function of the TCA cycle?

<p>ATP consumption (A)</p> Signup and view all the answers

The conversion of pyruvate to acetyl-CoA by pyruvate dehydrogenase is a reversible reaction.

<p>False (B)</p> Signup and view all the answers

Match the following TCA cycle intermediates with their corresponding metabolic roles:

<p>Oxaloacetate = Starting point and regeneration Citrate = Initial product of acetyl-CoA condensation α-Ketoglutarate = Precursor for amino acids and purines Succinyl-CoA = Precursor for haem synthesis</p> Signup and view all the answers

Which enzyme catalyzes the first committed step of the TCA cycle?

<p>Citrate Synthase (D)</p> Signup and view all the answers

During the TCA cycle, two molecules of ______ are produced from each molecule of acetyl-CoA.

<p>CO2</p> Signup and view all the answers

The isomerization reaction in the TCA cycle, converting citrate to isocitrate, is a key regulatory step.

<p>False (B)</p> Signup and view all the answers

Which of the following enzymatic reactions in the TCA cycle directly produces ATP (or GTP)?

<p>Succinyl-CoA Synthetase (D)</p> Signup and view all the answers

How many NADH molecules are generated from one turn of the TCA cycle?

<p>3</p> Signup and view all the answers

Red blood cells contain mitochondria and can therefore perform the TCA cycle.

<p>False (B)</p> Signup and view all the answers

Which enzyme in the TCA cycle is also part of the electron transport chain?

<p>Succinate Dehydrogenase (B)</p> Signup and view all the answers

The two main products of the TCA cycle that are fed into the electron transport chain are NADH and ______.

<p>FADH2</p> Signup and view all the answers

Briefly describe the role of oxaloacetate in the TCA cycle, and explain why it is important to regenerate it.

<p>Oxaloacetate combines with acetyl-CoA to initiate the cycle. Its regeneration is crucial for the continuation of the TCA cycle, allowing it to oxidize more acetyl-CoA and produce energy.</p> Signup and view all the answers

The reactions converting fumarate to malate and malate to oxaloacetate are both key regulatory steps in the TCA cycle.

<p>False (B)</p> Signup and view all the answers

Which of the following molecules is an anaplerotic substrate that 'tops up' the TCA cycle?

<p>Pyruvate (C)</p> Signup and view all the answers

The irreversible enzyme ______ catalyzes the carboxylation of pyruvate to form oxaloacetate.

<p>pyruvate carboxylase</p> Signup and view all the answers

Why is the conversion of isocitrate to alpha-ketoglutarate considered a key reaction in the TCA cycle?

<p>A key reaction, as it is the first decarboxylation step, resulting in the release of CO2 and the production of NADH, which is vital for energy production.</p> Signup and view all the answers

The TCA cycle is only involved in energy production and not in biosynthetic pathways.

<p>False (B)</p> Signup and view all the answers

Which of the following is a precursor for porphyrin ring synthesis?

<p>Succinyl CoA (A)</p> Signup and view all the answers

Alpha-ketoglutarate, an intermediate in the TCA cycle, can be converted to the amino acid ______ via transamination.

<p>glutamate</p> Signup and view all the answers

Why is the irreversible nature of certain TCA cycle steps important for the overall regulation of metabolism?

<p>The presence of irreversible steps ensures that the cycle proceeds in a forward direction. This determines the metabolic flux and the rate at which the TCA cycle operates, thus regulating energy production.</p> Signup and view all the answers

Increasing the levels of ATP and NADH typically stimulates the TCA cycle.

<p>False (B)</p> Signup and view all the answers

Besides ATP, what other high-energy intermediate is DIRECTLY produced in the reaction catalyzed by Succinyl-CoA synthetase during the TCA cycle?

<p>GTP (A)</p> Signup and view all the answers

The enzyme that catalyzes the reaction directly before the entry of Acetyl-CoA into the TCA cycle is ______.

<p>pyruvate dehydrogenase</p> Signup and view all the answers

Explain why the TCA cycle is considered amphibolic.

<p>It has both catabolic and anabolic functions. Catabolically, it oxidizes acetyl-CoA to produce energy. Anabolically, it provides intermediates for the synthesis of other molecules.</p> Signup and view all the answers

Suppose a researcher discovers a new inhibitor that specifically blocks the activity of aconitase. Which of the following outcomes would most likely be observed in cells treated with this inhibitor?

<p>Accumulation of citrate and decreased production of both NADH and FADH2. (B)</p> Signup and view all the answers

Imagine a scenario where a genetic mutation causes a complete loss of function in the malate dehydrogenase enzyme. How would this affect the cell's ability to perform gluconeogenesis, assuming all other enzymes are functioning normally and sufficient substrates are available?

<p>Gluconeogenesis will be severely impaired because the transport of oxaloacetate, required in gluconeogenesis, is disrupted. (B)</p> Signup and view all the answers

Flashcards

What is the TCA Cycle?

A series of chemical reactions used by all aerobic organisms to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins.

TCA Cycle: Alternative Names?

Krebs Cycle, Citric Acid Cycle, Tricarboxylic Acid Cycle, Common Terminal Pathway

TCA Cycle: Definition

Oxidation of acetyl CoA to CO2 and water

TCA Cycle: Location

Mitochondrial matrix

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TCA Cycle: Tissues

All tissues with mitochondria (not red blood cells or white muscle fibres)

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TCA Cycle: Functions

Energy trapping, biosynthesis of intermediates

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Pyruvate to Acetyl-CoA Conversion

It is catalysed by pyruvate dehydrogenase and converts pyruvate to acetyl-CoA

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Coenzyme A

An enzyme that produces a thioester bond with carboxylic acids

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Condensation Reaction

The first reaction of the TCA cycle. Oxaloacetate + Acetyl-CoA = Citrate

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Isomerisation

A reaction, using aconitase, that moves things around.

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First Loss of CO2

A reaction with a key enzyme that makes NADH and removes CO2.

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Irreversibility of key stages

Three enzyme steps are highly exergonic & irreversible: citrate synthase, isocitrate dehydrogenase, a-ketoglutarate dehydrogenase

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NADH and H+ Production

3 enzyme reactions produce NADH and H+

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FADH2 Production

1 enzyme reaction produces FADH2

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GTP Production

1 enzyme reaction produces GTP

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Study Notes

  • Lecture 14 is on the TCA Cycle of Biochemistry

TCA cycle

  • Also known as the Krebs cycle, Citric acid cycle, or Tricarboxylic acid cycle
  • The common terminal pathway for the catabolism of sugars, fats, and amino acids
  • Oxidation of acetyl CoA to CO2 and water
  • Located in the mitochondrial matrix in all tissues with mitochondria, except red blood cells or white muscle fibres
  • Functions in energy trapping and biosynthesis of intermediates

Summary of TCA cycle events

  • The events account for where carbon dioxide is lost and where carbon atoms are added into the cycle
  • The pathway starts with a 2-carbon molecule which combines with a 4-carbon molecule to create a 6-carbon molecule
  • Two carbons atoms are lost to get back to a 4 carbon molecule, to restart the cycle
  • The individual names of the enzymes and substrates do not need to be memorized
  • Uses a mnemonic device

Conversion of Pyruvate to Acetyl CoA

  • Catalyzed by pyruvate dehydrogenase, occurs in the link reaction
  • Result is 1 NADH and 1 CO2

Coenzyme A

  • Forms thioester bonds with carboxylic acids

(1) Condensation reaction

  • The first reaction to start the TCA cycle
  • This is a key reaction
  • Count the carbon atoms!

(2) Isomerisation

  • A less significant reaction involving moving things around

(3) First loss of CO2

  • This is a key reaction
  • First loss of CO2 during the cycle
  • Produces NADH

(4) Second loss of CO2

  • This is a key reaction
  • Second loss of CO2 during the cycle
  • Produces NADH

Why continue the cycle?

  • Acetyl CoA has only 2 carbon atoms and 2 carbons have already been lost through the previous two decarboxylation reactions
  • The the cycle regenerates oxaloacetate and also generate more high energy intermediates like NADH and FADH2

(5) Trapping thioester bond energy

  • Occurs as GTP
  • This is a key reaction
  • It produces ATP (as GTP)

(6) Conversion of succinate to fumarate

  • This is a key reaction
  • Produces FADH2

(7) Conversion of fumarate to malate

  • A less significant reaction involving just adding water

(8) Conversion of malate to oxaloacetate

  • This is a key reaction
  • Produces NADH
  • Re-forms OAA, now ready to start the cycle again!

Generation of ATP

  • The re-oxidation of NADH to NAD+ and FADH2 to FAD via the Electron Transport Chain results in synthesis of ATP from ADP and Pi (Oxidative Phosphorylation)

Energy yields of TCA cycle

  • Three enzyme reactions produce NADH and H+
  • One enzyme reaction produces FADH2
  • One enzyme reaction produces GTP
  • ATP yields = 3 x 3 ATP5 + 1 x 2 ATP + 1GTP or 10 ATP old numbers ATD new numbers

Energy yields from 1 molecule of glucose

  • Glycolysis: 2 ATP, 2NADH (2x2.5 = 5 ATP) 7 ATP
  • Link reaction: 1 NADH (do it 2x for each pyruvate) 5ATP
  • TCA Cycle: 10 ATP per turn (2 turns) 20 ATP

Irreversibility of key stages

  • 3 enzyme steps are highly exergonic & irreversible: citrate synthase, isocitrate dehydrogenase, and a-ketoglutarate dehydrogenase

Biosynthetic role of TCA cycle

  • Role in biosynthetic processes, in the production of for instance, other amino acids, purines, pyrimidines, aspartate, Glutamate & haem

Anaplerotic ‘topping up' of TCA cycle

  • Reintroduces key molecules, the pyrivate carboxylase reaction regenerates glucose from pyruvate

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