Detailed Notes on the Citric Acid Cycle and Cellular Respiration

• —Overview of Cellular Respiration

  • Process by which cells consume O2 and produce CO2.

  • Involves several stages:

    1. Glycolysis

    2. Pyruvate oxidation

    3. Citric Acid Cycle

    4. Oxidative phosphorylation

  • Provides more energy from glucose than glycolysis alone.

  • Used by animals, plants, and microorganisms, with an evolutionary origin around 2.5 billion years ago.

• Energy Changes in Glycolysis

  • Small amount of energy captured in glycolysis, ΔG’° = -146 kJ/mol.

  • Full oxidation of glucose yields ΔG’° = -2840 kJ/mol, producing 6 CO2 and 6 H2O.

Key Stages of Cellular Respiration

• Stage 1: Glycolysis - Occurs in the cytoplasm

  • Converts glucose into 2 pyruvate, producing NADH.

• Stage 2: Pyruvate Oxidation - Conversion of pyruvate to acetyl CoA

  • Produces NADH and CO2; requires the Pyruvate Dehydrogenase Complex (PDC).

• Stage 3: Citric Acid Cycle - Occurs in the mitochondrial matrix

  • Key reactions include:

    • Dehydrogenation

    • Decarboxylation

    • Substrate-level phosphorylation (GTP formation)

    • NADH and FADH2 production.

• Stage 4: Oxidative Phosphorylation - Involves electron transport chain and chemiosmosis

  • Produces large amounts of ATP via ATP synthase, utilizing the electrochemical gradient created by H+ pumping.

The Citric Acid Cycle Details

• Conversion of Pyruvate to Acetyl-CoA

  • Net reaction involves oxidative decarboxylation, requiring coenzymes (NAD+, CoA-SH).

  • Pyruvate Dehydrogenase Complex (PDC):

    • Composed of three enzymes: E1 (Pyruvate dehydrogenase), E2 (Dihydrolipoyl transacetylase), E3 (Dihydrolipoyl dehydrogenase).

    • Activity regulated by ATP levels.

• Citric Acid Cycle Mechanism

  • Steps overview:

    1. Formation of Citrate: Acetyl-CoA + oxaloacetate → citrate. (Citrate synthase catalyzes)

    2. Isomerization: Citrate to isocitrate via aconitase.

    3. Decarboxylation: Isocitrate to α-ketoglutarate, generating NADH and releasing CO2.

    4. α-Ketoglutarate to Succinyl-CoA: Another NADH and CO2 produced.

    5. Succinyl-CoA to Succinate: Produces GTP (or ATP).

    6. Succinate to Fumarate: FADH2 generated.

    7. Fumarate to Malate: Hydration step.

    8. Malate to Oxaloacetate: Produces NADH.

• Key Products from One Turn of the Cycle:

  • 3 NADH

  • 1 FADH2

  • 1 GTP (or ATP)

  • 2 CO2

Regulation of the Citric Acid Cycle

• Modulation of the cycle's activity is influenced by energy needs and metabolite availability:

  • Increases in NADH, ATP, and citrate often lead to a decrease in cycle activity.

  • Conversely, high ADP and high acetyl CoA can stimulate the cycle.

Oxidative Phosphorylation

• Mechanism of Electron Transport:

  • Electrons from NADH and FADH2 are passed through a series of carriers.

  • Energy released pumps H+ ions across the membrane, creating a proton gradient.

  • ATP synthase uses this gradient to produce ATP (approximately 30-32 ATP molecules from one glucose molecule).

• ATP Synthase Cycle:

  • Binding and release of ADP and Pi, leading to the generation of ATP via rotational mechanism.

Summary of Energy Yield from Glucose Degradation

• Total calculated ATP yield from glycolysis, PDC reaction, citric acid cycle, and oxidative phosphorylation is about 30-32 ATP molecules per glucose molecule, considering the efficiency and the involvement of NADH and FADH2 in ATP formation.