TCA BIOL 3200 Sp.25

Page 1: Introduction

• Prescott's Principles of Microbiology

• Tricarboxylic Acid Cycle (TCA)

• Authors: Joanne Willey, Kathleen Sandman

Page 2: Glycolysis Summary

• Primary pathway for converting one glucose molecule into two pyruvate molecules.

• Pathway generates:

  • 2 pyruvate

  • Net gain of 2 ATP (4 ATP produced - 2 ATP used for breakdown)

  • 2 NADH which will generate more ATP in TCA cycle.

Page 3: Carbon Sources in Catabolism

• Various carbon sources enter central pathways of catabolism:

  • Polysaccharides

  • Lipids

  • Disaccharides

  • Carbohydrates

  • Aromatics

• Pyruvate can be fermented to produce:

  • Acetate

  • Ethanol

  • Lactate

  • CO₂

  • H₂

• Acetyl-CoA enters the TCA cycle producing CO₂.

Page 4: TCA Cycle Overview

• Pyruvate is converted to carbon dioxide through the TCA cycle.

• Key aspects to analyze:

  • Reactions producing ATP/GTP and NADH

  • Generate precursor metabolites

  • Connection between glycolytic pathways and TCA cycle.

Page 5: Fate of Pyruvate

• Fermentation:

  • Recycling of NADH to NAD+

  • Produces acid and/or alcohol.

• TCA Cycle also creates additional precursor metabolites, NADH, and FADH2.

Page 6: Location of TCA Cycle

• Occurs in different locations:

  • Prokaryotes: Cytoplasm

  • Eukaryotes: Mitochondria

• Connects to glucose catabolism through the breakdown of pyruvate into acetyl-CoA and CO2.

• Acetyl-CoA combines with oxaloacetate to form citrate.

Page 7: Pyruvate Dehydrogenase Complex (PDC)

• Catalyzes conversion of pyruvate to acetyl-CoA.

• The reaction:

  • Pyruvate + NAD+ + CoA → Acetyl-CoA + CO2 + NADH + H+.

Page 8: Importance of PDC

• Directs glucose catabolism to respiration.

• Defects can lead to severe health issues, such as:

  • Myocardial infarction

  • Heart failure

  • Neurodegeneration

• Inhibition occurs due to increased levels of acetyl-CoA.

Page 9: Carbon Sources in Catabolism (Repeating Visual)

• Shows various carbon sources entering catabolism pathways heading to the TCA cycle.

Page 10: TCA Cycle Dynamics

• Acetyl-CoA combines with oxaloacetate to start the cycle.

• Hydrolysis provides energy for the chemical reactions

• NADH and FADH2 involvement and their role in the ETS (Electron Transport System).

Page 11: Pyruvate Processing Summary

• For each pyruvate oxidized:

  • PDC produces 1 CO2 and 1 NADH.

  • TCA Cycle produces:

    • 2 CO2, 3 NADH, 1 FADH2

    • 1 ATP (or GTP, functionally equivalent)

• Overall summary: Pyruvate to TCA Cycle outputs.

Page 12: Evolutionary Significance of TCA Cycle

• Originally evolved aiding in amino acid production:

  • Examples include conversions from 2-oxoglutarate to glutamate to glutamine and from oxaloacetate to aspartate to nucleotides.

• Links to biosynthesis.

• Some microbes (e.g., Treponema pallidum) abandoned TCA.

Page 13: Complete Oxidation of Glucose

• Overview of electron transfers from glycolysis through TCA cycle to the ETS.

• Shows electron carriage and output of ATP from pathways.

Page 14: Electron Carriers Yield

• Efficiency of electron carriers:

  • NADH = 3 ATP

  • FADH2 = 2 ATP

• Example: E. coli produces ATP from glucose processes.

Page 15: Glyoxylate Shunt

• Absence of glucose leads to catabolism of acetates or fatty acids through the Glyoxylate Shunt.

• The bypass conserves carbon for metabolism and reduces CO2 loss.

Page 16: Glyoxylate Bypass Details

• Mechanisms involved in converting substrates:

  • Acetyl-CoA to malate.

• Important for pathogens like Mycobacterium tuberculosis.

Page 17: Mycobacterium tuberculosis Overview

• Statistics on tuberculosis and its global impact.

• Pathogenicity linked to glycolytic processes and the Glyoxylate Bypass.

Page 18: Chapter Summary

• Summary of primary catabolic pathways (Fermentation, respiration, photoheterotrophy).

• Central role of the TCA cycle in metabolism and electron transport.