CHM260 Chapter 18_19

Stages of Cellular Respiration

  1. Stage 1: Formation of Acetyl-CoA

    • Involves the oxidation of fatty acids, glucose, and amino acids.

    • Produces Acetyl-CoA which is a key metabolite for energy production.

  2. Stage 2: Citric Acid Cycle (CAC)

    • Acetyl groups are oxidized in the CAC, producing energy-rich electron carriers (NADH and FADH2).

  3. Stage 3: Electron Transport and Oxidative Phosphorylation

    • Electrons from NADH and FADH2 enter the respiratory chain, reducing O2 to H2O, driving ATP production.

Properties of Acetyl-CoA

  • Acetyl-CoA is a pivotal molecule in metabolism, serving as a substrate for the citric acid cycle and biosynthesis of fatty acids and amino acids.

  • It contains a high-energy thioester bond that facilitates the transfer of acyl groups in various metabolic pathways.

Role of Pyruvate in Metabolism

  • Pyruvate is produced from glycolysis and acts as a critical junction metabolite.

  • Under anaerobic conditions, it is converted to lactic acid or ethanol.

  • Under aerobic conditions, it enters the mitochondria and is converted into Acetyl-CoA, which fuels the citric acid cycle, generating ATP and CO2.

Pyruvate Dehydrogenase (PDH) Complex

  • Located in the mitochondrial matrix, consisting of three enzymes (E1: Pyruvate decarboxylase, E2: Dihydrolipoyl transacetylase, E3: Dihydrolipoyl dehydrogenase) and five coenzymes (TPP, lipoic acid, FAD, CoA, NAD+).

  • PDH catalyzes the irreversible oxidative decarboxylation of pyruvate to form Acetyl-CoA, releasing CO2 and generating NADH.

Significance of the Citric Acid Cycle

  • The CAC is crucial for aerobic metabolism, transforming Acetyl-CoA into CO2 and high-energy electrons that fuel ATP production via oxidative phosphorylation.

  • It acts as a hub for integrating metabolic pathways, contributing to the biosynthesis of various metabolites.

Key Species and Energy Compounds in the CAC

  • Key Species: Acetyl-CoA (2 carbon atoms enter), CO2 (2 carbon atoms leave).

  • Energy Compounds: Per cycle, it produces 3 NADH, 1 FADH2, and 1 GTP (or ATP). These compounds are essential for ATP synthesis through the electron transport chain.

ATP Yield from Oxidation of Acetyl-CoA

  • The complete oxidation of one molecule of glucose yields approximately 32 ATP, which includes contributions from glycolysis, the PDH complex, and the citric acid cycle, indicating that each Acetyl-CoA can yield multiple ATP equivalents.

Concept of a Metabolon in the Citric Acid Cycle

  • The CAC enzymes can form temporary functional complexes (metabolons) that enhance substrate channeling, improving metabolic efficiency and coordination of reactions, particularly through critical intermediates.

  • Key enzymes like MDH and CS are critical for maintaining the flux of the cycle.

Regulation of PDH and the Citric Acid Cycle

  • The regulation of PDH is critical and occurs through covalent modifications (phosphorylation/dephosphorylation), where ATP levels affect PDH activity.

  • The citric acid cycle is tightly regulated based on cellular energy needs, where metabolite concentrations can influence the flow through key catalytic