Introduction to Metabolism

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Introduction to Metabolism

• Biology is applied Chemistry!

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Metabolism

• Metabolism is the totality of an organisms
  chemical reactions
• Metabolism is an emergent property of life that
  arises from interactions between molecules within
  the cell
• Catabolic pathways release energy by breaking
  down complex molecules into simpler compounds
• Anabolic pathways consume energy to build complex
  molecules from simpler ones

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Energy (energy concepts video)

• Energy The capacity to do work
• Kinetic Energy The energy to do work
• Heat (thermal energy) is kinetic energy
  associated with random movement of atoms or
  molecules
• Potential energy Energy that matter possesses
  because of its location or structure
• Chemical energy is potential energy available for
  release in a chemical reaction

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• Organisms are energy transformers
• Sunlight ? ? Glucose ? ? ? Life functions
• (kinetic) (potential-stored) (kinetic)
• Bioenergetics is the study of how organisms
  manage their energy resources

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Laws of Thermodynamic

• 1st Conservation of Energy. Energy can not be
  created or destroyed. (but it can be transferred
  or transformed)
• 2nd Every energy transfer or transformation
  increases the Entropy of the universe.
• During every energy transfer or transformation,
  some energy is unusable, and is often lost as
  heat

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Exergonic reactions release energy
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Endergonic reactions require energy
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Energy Coupling

• Energy Coupling use of an exergonic process to
  drive an endergonic process.
• ATP is the energy coupler / currency of energy
  coupling.

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ATP --------? ADP Pi energy
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Metabolic Pathways

• A metabolic pathway begins with a specific
  molecule and ends with a product.
• Each step is catalyzed by a specific enzyme

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Enzymes (enzyme video overview)

• Biological catalysts
• A catalyst is a chemical agent that speeds up a
  reaction without being consumed by the reaction
• Usually proteins
• Lower the activation energy of a reaction
• Every chemical reaction between molecules
  involves bond breaking and bond forming
• The initial energy needed to start a chemical
  reaction is called the activation energy (EA)

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Enzymes

• An enzymes activity can be affected by
• Environmental factors, such as temperature and pH

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Enzymes are substrate specific

• Active site restricted region of the enzyme
  molecule which binds to the substrate
• Some require Cofactors
• Inorganic (metal ions Zn, Fe, Cu)
• Organic also called coenzymes (most vitamins
  are coenzymes)

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Mechanism of Action (generalized)

• 1. Substrate binds at enzyme active site
•  
• 2. Enzyme changes shape in response to the
  substrate
• (Enhanced fit or Induced fit)
•  
• 3. Shape change brings chemical groups of
  molecules into positions to
• enhance the reaction. Bonds break/bonds form
•  
• 4. Product formed which no longer fits the
  active site and is therefore released
•  
• 5. Enzyme returns to original shape and is ready
  to go again!

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Controls on enzyme activity

• Substrate concentration
• Inhibitors
• Competitive inhibitors
• Noncompetitive inhibitors

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Inhibitors
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Real WorldAntifreeze (ethylene glycol) poisoning

• Dogs and cats are attracted to ethylene glycol by
  its sweet taste. Animals will voluntarily drink
  ethylene glycol if antifreeze is spilled or leaks
  onto garage floors or driveways.
• Perhaps as many as 10,000 dogs and cats are
  victims of accidental poisoning by automobile
  antifreeze every year

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Symptoms of ethylene glycol poisoning

• Depression, vomiting, incoordination, excessive
  urination, excessive thirst, and muscle
  twitching. Within 30 minutes of ingestion.
• In as little as 12 to 36 hours, severe kidney
  dysfunction characterized by swollen, painful
  kidneys and the production of minimal to no
  urine, may occur.
• The dog or cat may be seizuring, be comatose.
  Or dead!
• WHY?

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The Problem

• Ethylene glycol itself is not the problem per se.
  
• The PROBLEM is the toxic products that are
  created by liver enzymes (alcohol dehydrogenase)
  acting upon the ethylene glycol.
• These metabolites cause acidosis (the blood
  becomes dangerously acidic) and destruction of
  kidney function.

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The SolutionLets get Rover hammered!!!!

• Hooray for Competitive inhibition!
• Ethanol can be used as a competitive inhibitor.
  It can outcompete ethylene glycol for the active
  site of the alcohol dehydrogenase enzyme.
• If the enzyme molecules are busy with ethanol
  they wont be available to turn ethylene glycol
  into toxic metabolites.

Fomepizole, an inhibitor of alcohol dehydrogenase
is replacing the use of ethanol.
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Allosteric regulation

• Allosteric site specific receptor site on some
  part of the enzyme molecule other than the active
  site
• Activators as well as inhibitors may exist

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Feedback Inhibition

• In feedback inhibition, the end product of a
  metabolic pathway shuts down the pathway
• Feedback inhibition prevents a cell from wasting
  chemical resources by synthesizing more product
  than is needed