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Page 1: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Metabolism

Chapter 5

Page 2: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Metabolism

This is a simpleDiagram of theMetabolic pathwaysFor TryptophanAlone.

Page 3: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Central Metabolism vs. Secondary Metabolism

Metabolism

Central Metabolism

Secondary Metabolism

Processing of Glucose Everything Else

Page 4: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Glucose

• C6H12O6

• One of many isomer for that formula• The most abundant carbohydrate on

the planet• The most ancient metabolic pathway

in extant life.• How can we argue this point? What

evidence could we cite?

Page 5: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

The Three Main Paths of Glucose Metabolism

GlycolysisO2

utilized?

Kreb’s Cycle ETC

Fermentation

Anaerobic Respiration

ETC utilized?

No

Yes

No

Yes

ETC = Electron Transfer Chain

Page 6: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Glycolysis

• C6H12O6 + 2 NAD+ + 2 ADP + 2 Pi 2 Pyruvate + 2 NADH + 2 ATP

• Produces an excess of usable energy (ATP) and some high energy electron carriers (NADH)

• Common to almost all life

Page 7: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Stages of Glycolysis

• Activation of Glucose• Fragmentation• Energy Harvest

• These are not the detailed steps, but rather the general conceptualized stages I want you to learn in some detail.

Page 8: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Glycolysis - Activation

Glucose Fructose 1,6-bisphosphate

ATP

ATP

ADP

ADP

This turns fairly unreactive glucose into a more reactive molecule

Page 9: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Glycolysis - Fragmentation

Fructose 1,6-bisphosphate

G3P

G3PG3P = Glyceraldehyde 3-Phosphate

This stage fragments the six-carbon sugar into two three-carbon molecules

Page 10: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Glycolysis – Energy Harvest

G3P

G3P

ADP

ADP

NAD+

NAD+

ATP

ATP

ATP

ATP

ADP

ADP

Pyruvate

Pyruvate

NADH

NADH

Net Production = 2ATP and 2 NADH

Page 11: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Outcomes for Glycolysis

• Energy Production– Net 2 ATP (easily usable biochemical

energy)– 2 NADH (high energy electron carrier,

harder to use in the cell)

• 2 Molecules of Pyruvate (3-carbon)• Pathway cannot continue without a

constant supply of NAD+

Page 12: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

The Big Problem…

How do you convert NADH back into NAD+?

Page 13: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Aerobic Respiration

GlycolysisO2

utilized?

Kreb’s Cycle ETC

Fermentation

Anaerobic Respiration

ETC utilized?No

Yes

No

Yes

Page 14: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Aerobic Respiration

• The most efficient form of Glucose metabolism

• Requires Oxygen• Total Yield in ATP (including Glycolysis)– Prokaryotes = 38 ATP / Glucose– Eukaryotes = 36 ATP / Glucose (theoretical)

• Handled in Two Stages– Kreb’s Cycle (or TCA Cycle)– Electron Transport Chain

Page 15: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Kreb’s Cycle

• Located in Cytoplasm of Prokaryotes and the Matrix of the Mitochondria in Eukaryotes.

• Breaks Pyruvate down into CO2

• Generates the following (per pyruvate)– 3 CO2

– 4 NADH (including pyruvate decarboxylation)– 1 FADH2

– 1 ATP

Page 16: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Kreb’s Cycle

Pyruvate Acetyl-CoA

CO2

CoA

Kreb’s Cycle

CO2 CO2

CoA

NADH

NADH

NADH FADH2

ATP

ADP

NADH

Page 17: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Outcomes for Kreb’s Cycle

• Glucose is completely reduced to carbon dioxide.

• All the energy that can be extracted is in the form of ATP, NADH, or FADH2

• The ATP are directly utilized, but the electron carriers have to be reduced through another step.

Page 18: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Electron Transport Chain

• In the plasma membrane of prokaryotes and the inner membrane of the mitochondria of eukaryotes.

• A series of proteins that indirectly convert the electron energy of NADH and FADH2 into ATP.

Page 19: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

ETC - Diagram

Matrix or Cytoplasm

Intermembrane SpaceOr Exterior of Cell

NADH +H+ NAD+

FADH2 FAD

1. The cofactors are Reduced and electrons Enter the ETC

Matrix or Cytoplasm

Intermembrane SpaceOr Exterior of Cell

H+2. Movement of electronsPower the pumping of H+ ions

Matrix or Cytoplasm

Intermembrane SpaceOr Exterior of Cell

H+H+

3. Continued movement through the chain powersFurther H+ ion pumps

Matrix or Cytoplasm

Intermembrane SpaceOr Exterior of Cell

2 H+ + ½ O2 H20

4. Terminal Electron Acceptor is Oxygen

Page 20: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Outcome of ETC

• NADH and FADH2 are reduced back to NAD+ and FAD, which can be recycled into earlier stages.

• Hydrogen ions have been pumped from the inside of the membrane to the outside.

• Have we harvested energy as ATP?• NO, we have produced a form of potential

energy, a hydrogen ion gradient.

Page 21: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Oxidative Phosphorylation

Matrix or Cytoplasm

Intermembrane spaceOr Exterior of cell H+

H+H+

H+

H+

H+

ATP Synthase Enzyme

1. A gradient of H+ ionsNeed a way through the Membrane, and the ATPSynthase enzyme has aH+ ion specific tunnel.

Matrix or Cytoplasm

Intermembrane spaceOr Exterior of cell H+

H+

H+

H+

H+

H+

ATP Synthase EnzymeADP

ATP

2. Passage of an H+ ionThrough the system Powers the conversionOf ADP+Pi to ATP.

Page 22: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Outcome of Oxidative Phosphorylation

• Harvests the hydrogen gradient to produce ATP.

• For each NADH you generate 3 H+ ions (3 ATP) for each FADH2 you get 2 H+ ions (2 ATP)

Page 23: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Summary of Aerobic Respiration

• Inputs– 1 Glucose– 36 or 38 ADP– 36 or 38 Pi

– 6 O2

• Outputs– 6 CO2

– 6 H20

– 36 or 38 ATP

Page 24: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

So what do we do without oxygen?

GlycolysisO2

utilized?

Kreb’s Cycle ETC

Fermentation

Anaerobic Respiration

ETC utilized?No

Yes

No

Yes

Page 25: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Fermentation

• Produces no net energy after Glycolysis

• Reduces NADH back to NAD+ through directly shunting high-energy electrons into an organic terminal electron acceptor.

• The terminal electron receptor represents a significant amount of wasted energy.

Page 26: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Example of Fermentation-Ethanol

Pyruvate Acetaldehyde

CO2

NADH

Ethanol

NAD+

Page 27: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Anaerobic Respiration

• Similar in concept to aerobic respiration• Utilizes an ETC or direct Electron Transfer• Terminal Electron Acceptor is an inorganic

or, less commonly, an organic molecule• Final energy production is accomplished

through Chemiosmosis• Net Energy Production after Glycolysis• Prokaryotic Reactions

Page 28: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Examples of Anaerobic Respiration Reactions

• Fe+3 Fe+2 (ETC driven)• Mn+4 Mn+2 (ETC driven)• UO2

+2 UO2 (ETC driven)

• SO4 H2S (Direct Electron Transfer)

• CO2 CH4 (Direct Electron Transfer)

Page 29: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Comparison of Metabolisms

• Energy Produced per Glucose– Aerobic Respiration – 36/38 ATP– Fermentation – 2 ATP– Anaerobic Respiration – between 2 and 36

ATP

• Byproducts– Aerobic Respiration – CO2 and H2O

– Fermentation – High Energy Organic– Anaerobic Respiration – Low Energy

Inorganic or Organic

Page 30: Metabolism Chapter 5. Metabolism This is a simple Diagram of the Metabolic pathways For Tryptophan Alone. Copyright 2009, John Ireland

Copyright 2009, John Ireland

Terminology

• Source of Carbon– Heterotroph – organic molecules– Autotroph – carbon dioxide

• Source of Energy– Chemotroph – chemical reactions– Phototroph – sunlight

• There are other options, but they are of little importance in medical microbiology.