Introduction to Metabolism

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• Introduction to Metabolism

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• Metabolism is the sum of an organisms chemical
  reactions
• Metabolism is an emergent property of life that
  arises from interactions between molecules within
  the cell

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• A metabolic pathway begins with a specific
  molecule and ends with a product
• The product of one reaction is substrate of the
  next
• Each step is catalyzed by a specific enzyme

BIOCHEMICAL PATHWAYVIDEO
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ENZYMES THAT WORK TOGETHER IN A PATHWAY CAN BE
Concentrated in specific location
Covalently bound incomplex
Soluble with free floating intermediates
Attached toa membranein sequence
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• CATABOLIC PATHWAY (CATABOLISM)Release of energy
  by the breakdown of complex molecules to simpler
  compoundsEX digestive enzymes break down food
• ANABOLIC PATHWAY (ANABOLISM)consumes energy to
  build complicated molecules from simpler onesEX
  linking amino acids to form proteins

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Krebs Cycle connects the catabolic and anabolic
pathways
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Forms of Energy

• ENERGY capacity to cause change
• Energy exists in various forms (some of which
  can perform work)
• Energy can be converted from one form to another

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• KINETIC ENERGY energy associated with motion
• 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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Diving converts potential energy to kinetic
energy.
On the platform, the diver has more potential
energy.
In the water, the diver hasless potential energy.
Climbing up converts kinetic energy of muscle
movement to potential energy.
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• THERMODYNAMICS the study of energy
  transformations
• CLOSED system (EX liquid in a thermos)
  isolated from its surroundings
• OPEN system energy matter can be transferred
  between the system and its surroundings
• Organisms are open systems

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The First Law of Thermodynamics

• energy of the universe is constant
• Energy can be transferred and transformed
• Energy cannot be created or destroyed
• The first law is also called the principle of
  CONSERVATION OF ENERGY

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The Second Law of Thermodynamics

• During every energy transfer or transformation
• entropy (disorder) of the universe INCREASES
• some energy is unusable, often lost as heat

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Second law of thermodynamics
First law of thermodynamics
Chemical energy
Heat
CO2
H2O
ORGANISMS are energy TRANSFORMERS! Spontaneous
processes occur without energy input they can
happen quickly or slowly For a process to occur
without energy input, it must increase the
entropy of the universe
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Free-Energy Change (?G) can help tell which
reactions will happen

• ?G change in free energy ?H change in total
  energy (enthalpy) or change ?S entropy T
  temperature
• ?G ?H - T?S
• Only processes with a negative ?G are spontaneous
• Spontaneous processes can be harnessed to perform
  work

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Exergonic and Endergonic Reactions in Metabolism

• EXERGONIC reactions (- ?G)
• Release energy
• are spontaneous
• ENDERGONIC reactions ( ?G)
• Absorb energy fromtheir surroundings
• are non-spontaneous

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Concept 8.3 ATP powers cellular work by coupling
exergonic reactions to endergonic reactions

• A cell does three main kinds of work
• Mechanical
• Transport
• Chemical
• In the cell, the energy from the exergonic
  reaction of ATP hydrolysis can be used to drive
  an endergonic reaction
• Overall, the coupled reactions are exergonic

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ATP (adenosine triphosphate) is the cells
renewable and reusable energy shuttle ATP
provides energy for cellular functions Energy to
charge ATP comes from catabolic reactions
Adenine
Phosphate groups
Ribose
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P
P
P
Adenosine triphosphate (ATP)
H2O

P
P
P
Energy

i
Adenosine diphosphate (ADP)
Inorganic phosphate
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ATP
Energy for cellular work provided by the loss
ofphosphate from ATP
Energy from catabolism (used to charge upADP
into ATP
P
ADP

i
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Endergonic reaction DG is positive, reaction is
not spontaneous
NH2
NH3
DG 3.4 kcal/mol

Glu
Glu
Ammonia
Glutamine
Glutamic acid
Exergonic reaction DG is negative, reaction is
spontaneous
P
DG 7.3 kcal/mol
ATP
ADP
H2O


i
Coupled reactions Overall DG is
negative Together, reactions are spontaneous
DG 3.9 kcal/mol
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P
i
P
Motor protein
Protein moved
Mechanical work ATP phosphorylates motor proteins
Membrane protein
ADP
ATP

P
i
P
P
i
Solute transported
Solute
Transport work ATP phosphorylates transport
proteins
P
NH2
NH3
P


Glu
i
Glu
Reactants Glutamic acid and ammonia
Product (glutamine) made
Chemical work ATP phosphorylates key reactants
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Every chemical reaction between molecules
involves bond breaking and bond
forming ACTIVATION ENERGY amount of energy
required to get chemical reaction
started Activation energy is often supplied in
the form of heat from the surroundings
Free energy animation
ITS LIKE PUSHING A SNOWBALL UP A HILL . . .
Once you get it up there, it can roll down by
itself
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The Activation Energy Barrier
A
B
C
D
Transition state
EA
A
B
Free energy
C
D
Reactants
A
B
DG lt O
C
D
Products
Progress of the reaction
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• CATALYST a chemical agent that speeds up a
  reaction without being consumed by the reaction
• ENZYMES biological catalystsMost enzymes are
  PROTEINS Exception ribozymes (RNA)

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Course of reaction without enzyme
EA without enzyme
EA with enzyme is lower
Reactants
Free energy
Course of reaction with enzyme
DG is unaffected by enzyme
Products
Progress of the reaction
ENZYMES work by LOWERING ACTIVATION ENERGY
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ENZYMES LOWER ACTIVATION ENERGY BY

• Orienting substrates correctly
• Straining substrate bonds
• Providing a favorable microenvironment
• Enzymes change
  ACTIVATION ENERGY but NOT energy of
  REACTANTS or PRODUCTS

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ENZYMES

• Most are proteins
• Lower activation energy
• Specific
• Shape determines function
• Re-usable
• Unchanged by reaction

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• The REACTANT that an enzyme acts on
  SUBSTRATE
• Enzyme substrate ENZYME-SUBSTRATE
  COMPLEX
• Region on the enzyme where the substrate binds
  ACTIVE SITE
• Substrate held in active site by WEAK
  interactions (ie. hydrogen and ionic bonds)

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TWO MODELS PROPOSED

• LOCK KEYActive site on enzymefits substrate
  exactly
• INDUCED FITBinding of substrate causes changein
  active site so it fits substratemore closely

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Enzyme Activity can be affected by

• General environmental factors, such as
  temperature, pH, salt concentration, etc.
• Chemicals that specifically influence the enzyme

See a movie
Choose narrated
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• TEMPERATURE ENZYME ACTIVITY
• Each enzyme has an optimal temperature at which
  it can function (Usually near body temp)

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Increasing temperature increases the rate of an
enzyme-catalyzed reaction up to a point. Above a
certain temperature, activity begins to decline
because the enzyme begins to denature.
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pH and ENZYME ACTIVITYEach enzyme has an optimal
pH at which it can function
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• COFACTORS non-protein enzyme helpers
• EX Zinc, iron, copper
• COENZYMES organic enzyme helpers
• Ex vitamins

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SUBSTRATE CONCENTRATION ENZYME ACTIVITY
V MAX
?
Adding substrate increases activity up to a point
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REGULATION OF ENZYME PATHWAYS

• GENE REGULATIONcell switches on or off the genes
  that code for specific enzymes

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REGULATION OF ENZYME PATHWAYS

• FEEDBACK INHIBITIONend product of a pathway
  interacts with and turns off an enzyme
  earlier in pathway
• prevents a cell from wasting chemical resources
  by synthesizing more product than is needed

FEEDBACK INHIBITION
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• NEGATIVE FEEDBACK
• An accumulation of an end product slows the
  process that produces that product

Example sugar breakdown generates ATP excess
ATP inhibits an enzyme near the beginning of the
pathway
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• POSITIVE FEEDBACK (less common)
• The end product speeds up production

EXAMPLE Chemicals released by platelets that
accumulate at injury site, attract MORE
platelets to the site.
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REGULATION OF ENZYME ACTIVITY

• ALLOSTERIC REGULATIONproteins function at one
  site is affected by binding of a regulatory
  molecule at another site
• Allosteric regulation can inhibit or stimulate an
  enzymes activity

Allosteric enzyme inhibition
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SOME ALLOSTERIC ENZYMES HAVE MULTIPLE SUBUNITS

• Each enzyme has active and inactive forms
• The binding of an ACTIVATOR stabilizes the
  active form
• The binding of an INHIBITOR stabilizes the
  inactive form

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Binding of one substrate molecule to active site
of one subunit locks all subunits in active
conformation.
Substrate
Stabilized active form
Inactive form
COOPERATIVITY another type of allosteric
activation
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COOPERATIVITY form of allosteric regulation
that can amplify enzyme activity Binding of one
substrate to active site of one subunit locks all
subunits in active conformation
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Enzyme Inhibitors
COMPETITIVE inhibitor REVERSIBLE Mimics
substrate and competes with substrate for active
site on enzyme
ENZYMEANIMATION
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Enzyme Inhibitors

• NONCOMPETITIVE inhibitors bind to another part of
  an enzyme, causing the enzyme to change shape and
  making the active site less effective

ENZYMEANIMATION
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