Krebs Cycle Overview

Questions and Answers

What happens to pyruvate dehydrogenase in cases of deficiency of pyruvate dehydrogenase phosphatase?

It is dephosphorylated and becomes active.

It is always phosphorylated and remains inactive. (correct)

It converts glucose directly into pyruvate.

It converts pyruvate into acetyl-CoA.

Which condition is associated with the deficiency of pyruvate dehydrogenase phosphatase?

Glucose intolerance

Krebs cycle activation

Acetyl-CoA accumulation

Lactic acidosis (correct)

What are the anaplerotic reactions primarily responsible for?

Replenishing intermediates in the TCA cycle (correct)

Converting lactic acid to glucose

Breaking down intermediates in the TCA cycle

Increasing ATP production

Which of the following best describes the Krebs cycle?

It is an amphibolic pathway. Signup and view all the answers

Which is NOT a consequence of pyruvate dehydrogenase phosphatase deficiency?

Increased tissue function Signup and view all the answers

Which substances are replenished by anaplerotic reactions in the TCA cycle?

Intermediates of the TCA cycle Signup and view all the answers

What is the primary effect of pyruvate always being phosphorylated?

It makes pyruvate dehydrogenase inactive. Signup and view all the answers

What role does malate play in the replenishing reactions?

It is an intermediate in the Krebs cycle. Signup and view all the answers

Which textbook is NOT suggested for further reading on this topic?

Physics in Biological Systems Signup and view all the answers

How does lactic acidosis affect the central nervous system?

It disrupts tissue function. Signup and view all the answers

Study Notes

Introduction to Krebs Cycle

Also known as the Citric Acid Cycle or Tricarboxylic Acid Cycle.
Discovered by Hans Adolf Krebs (1900-1981).
A series of enzymatic reactions utilized by aerobic organisms to generate cellular energy.

Function and Importance

Central metabolic pathway linking various metabolic pathways.
Final oxidative pathway for metabolizing carbohydrates, proteins, and fats.
Oxidizes acetyl CoA to produce CO2, H2O, ATP, and reduced coenzymes (FADH, NADH).

Cellular Respiration

Process of converting biochemical energy from nutrients into ATP.
Comprises three main stages, with the Krebs cycle as a key component.

Link Between Glycolysis and Krebs Cycle

Pyruvate is transported from the cytosol to mitochondria.
Oxidative decarboxylation of pyruvate forms acetyl-CoA, facilitated by the Pyruvate Dehydrogenase complex.

Pyruvate Dehydrogenase Complex

Composed of three enzymes and five cofactors.
Essential for converting pyruvate to acetyl-CoA.
Deficiency leads to elevated lactate and pyruvate levels, potentially resulting in acidosis and neurological issues.

Cofactors and Their Deficiencies

Key cofactors: Thiamine (TPP), Niacin (NAD), Riboflavin (FAD), Pantothenic Acid (CoA).
Thiamine deficiency can cause neurological and cardiac disorders (Beriberi), impairing the oxidation of pyruvate.

Reactions of the TCA Cycle

Step 1: Formation of citrate through a condensation reaction.
Step 2: Isomerization to isocitrate.
Step 3: Formation of α-ketoglutarate (α-KG).
Step 4: Decarboxylation to succinyl-CoA, generating NADH.
Step 5: Formation of succinate, producing GTP/ATP via substrate-level phosphorylation.
Step 6: Conversion to fumarate, inhibited by malonate.
Step 7: Hydration to malate.
Step 8: Regeneration of oxaloacetate.

Energy Yield

Overall reaction generates ATP and reduced coenzymes that drive ATP production in the electron transport chain.
One cycle of the Krebs cycle yields a total of approximately 10 ATP from one acetyl-CoA.

Regulation of the Krebs Cycle

Influenced by substrate availability (Acetyl-CoA and oxaloacetate).
Inhibition by accumulating products and allosteric feedback, particularly a high NADH/NAD+ ratio.
Covalent modifications can also impact enzyme activity.

Amphibolic Nature

Serves both catabolic (energy-producing) and anabolic (biosynthetic) functions.
Involves anaplerotic reactions that replenish intermediates to maintain metabolic balance during varying demands.