metabolism chapter 5. metabolism this is a simple diagram of the metabolic pathways for tryptophan...
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Metabolism
Chapter 5
Copyright 2009, John Ireland
Metabolism
This is a simpleDiagram of theMetabolic pathwaysFor TryptophanAlone.
Copyright 2009, John Ireland
Central Metabolism vs. Secondary Metabolism
Metabolism
Central Metabolism
Secondary Metabolism
Processing of Glucose Everything Else
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?
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
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
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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.
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Glycolysis - Activation
Glucose Fructose 1,6-bisphosphate
ATP
ATP
ADP
ADP
This turns fairly unreactive glucose into a more reactive molecule
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Glycolysis - Fragmentation
Fructose 1,6-bisphosphate
G3P
G3PG3P = Glyceraldehyde 3-Phosphate
This stage fragments the six-carbon sugar into two three-carbon molecules
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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
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+
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The Big Problem…
How do you convert NADH back into NAD+?
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Aerobic Respiration
GlycolysisO2
utilized?
Kreb’s Cycle ETC
Fermentation
Anaerobic Respiration
ETC utilized?No
Yes
No
Yes
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
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
Kreb’s Cycle
Pyruvate Acetyl-CoA
CO2
CoA
Kreb’s Cycle
CO2 CO2
CoA
NADH
NADH
NADH FADH2
ATP
ADP
NADH
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.
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.
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
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.
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.
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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)
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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
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
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.
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Example of Fermentation-Ethanol
Pyruvate Acetaldehyde
CO2
NADH
Ethanol
NAD+
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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
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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)
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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
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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.