Cellular Respiration & Krebs Cycle Study Notes

Lecture 05: Cellular Respiration & Krebs Cycle

A Little Krebs Cycle History

  • Discovered: The Krebs Cycle was discovered by Hans Krebs in 1937.

  • Nobel Prize: Krebs received the Nobel Prize in Physiology or Medicine in 1953 for his discovery.

  • Background: He was forced to leave Germany before World War II due to his Jewish heritage.

Learning Goals

  • Master fundamental concepts of cellular respiration.

  • Understand the three stages of cellular respiration and their functions.

  • Learn about the structural features of mitochondria and their functional relevance.

  • Explore evolutionary aspects of mitochondria and mitochondrial genetics.

  • Understand the importance of Acetyl CoA, NADH, and FADH in cellular respiration.

  • Examine the eight reactions, the enzymes involved, and key regulations of the Krebs Cycle.

  • Discuss the important roles of mitochondria in biosynthesis and anaplerosis.

Outlines

I. Overview of Cellular Respiration
II. Reactions & Regulation of TCA Cycle
III. Biosynthetic Function of TCA cycle

I. Overview of Cellular Respiration

  1. Three Stages of Cellular Respiration

    • Oxidation of Reduced Carbon Sources.

    • Mitochondria: Known as the powerhouses of cells.

    • Acetyl-CoA: The major direct fuel input for the TCA Cycle.

1. Stages of Cellular Respiration

  • Stage #1: Acetyl-CoA Production

    • All metabolic pathways lead to the formation of Acetyl-CoA.

    • Generates NADH and FADH2 as byproducts.

    • Conversion of glucose results in CO2 + ATP.

  • Stage #2: Acetyl-CoA Oxidation

    • Electrons are placed onto electron carriers.

    • The Krebs Cycle (also referred to as citric acid cycle or TCA cycle) enters here.

    • Focuses on energy transfer through electron movement.

    • Key electron carriers are FAD/NAD+.

  • Stage #3: Electron Transport Chain (ETC) & Oxidative Phosphorylation

    • Electrons are traded for ATP through various reactions.

    • Major ATP product generation occurs here.

    • Reactants include NADH and FADH2 and produce H2O using O2.

II. Reactions & Regulation of TCA Cycle

Overview

  • Mitochondria: Site of cellular respiration; dubbed the powerhouse of cells.

Structural Features of Mitochondria

  • Double Membrane Structure: Organelles possess a double membrane, enhancing functionality.

  • Mitochondrial Genome: Important for understanding mitochondrial function and genetics.

Importance of Acetyl-CoA

  • Direct Fuel: Acetyl-CoA is crucial for the TCA Cycle and serves as an activated form of acetate.

  • Biosynthesis Substrate: Acts as a key substrate in various biosynthetic pathways.

  • Transport Limitations: Cannot be converted into glucose in humans and is not transported across biomembranes.

General Reaction Equation for TCA Cycle

  • Overall, the TCA cycle can be summarized as:

    • extAcetyl−CoA+3extNAD++extFAD+extGDP+extP<em>i+2extH</em>2extO<br>ightarrow3extNADH+extFADH<em>2+extGTP+2extCO</em>2ext{Acetyl-CoA} + 3 ext{NAD}^+ + ext{FAD} + ext{GDP} + ext{P}<em>{i} + 2 ext{H}</em>2 ext{O} <br>ightarrow 3 ext{NADH} + ext{FADH}<em>2 + ext{GTP} + 2 ext{CO}</em>2

Steps and Enzymes of the TCA Cycle

  1. Citrate Synthesis

    • Reaction: Acetyl-CoA + Oxaloacetate → Citrate

    • Enzyme: Citrate Synthase

    • Gibbs Free Energy (ΔG°’): −32.2extkJ/mol-32.2 ext{ kJ/mol} (exergonic reaction)

  2. Isomerization

    • Citrate undergoes transformation to isocitrate

    • Enzyme: Aconitase

    • ΔG°’ varies based on conditions and specific reaction pathways.

  3. Isocitrate to Alpha-Ketoglutarate

    • Oxidation reaction releasing CO2 and producing NADH.

    • Enzyme: Isocitrate Dehydrogenase.

  4. Alpha-Ketoglutarate to Succinyl-CoA

    • Oxidative decarboxylation; a significant regulatory point.

    • Enzyme: Alpha-Ketoglutarate Dehydrogenase.

    • Generates NADH and releases CO2.

  5. Succinyl-CoA to Succinate

    • Substrate-level phosphorylation to produce GTP.

    • Enzyme: Succinyl-CoA Synthetase.

  6. Succinate to Fumarate

    • Oxidation of succinate results in FADH2 production.

    • Enzyme: Succinate Dehydrogenase.

  7. Fumarate to Malate

    • Addition of water (hydration).

    • Enzyme: Fumarase.

  8. Malate to Oxaloacetate

    • Final reaction regenerating oxaloacetate and producing another NADH.

    • Enzyme: Malate Dehydrogenase.

III. Biosynthetic & Anaplerotic Functions of TCA Cycle

Overview

  • Acetyl-CoA, oxaloacetate, and other intermediates serve as crucial substrates for biosynthesis.

Four Major Pathways for Biosynthesis

  1. Citrate (6C) to fatty acids/cholesterol.

  2. Alpha-Ketoglutarate (5C) to glutamate and glutamine.

  3. Oxaloacetate (4C) to aspartate and asparagine (leading to gluconeogenesis).

  4. Succinyl-CoA to porphyrins and heme.

Importance of Anaplerotic Reactions

  • Anaplerotic reactions replenish TCA intermediates that may be depleted, ensuring continuity of the cycle:

    • Example: Pyruvate Carboxylase converts pyruvate to oxaloacetate for re-entry into the TCA cycle.

    • Role of Biotin in CO2 transport during the reaction.

Glossary

  • Acyl Carrier Protein (ACP): A protein variant facilitating fatty acid synthesis.

  • Anaerobic Metabolism: Metabolic pathways utilizing substances other than oxygen for energy.

  • Anaplerosis: Refers to reactions that refill TCA cycle intermediates.

  • Oxidative phosphorylation: A process where ATP is formed as electrons are transferred to oxygen.

  • Tricarboxylic acid cycle (TCA): Another name for the Krebs cycle, focusing on tricarboxylic acid intermediates.