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_____CH. 6_
• Chapter 6~
An Introduction to
Metabolism
Metabolism/Bioenergetics
• Metabolism: The totality of an organism’s
chemical processes; managing the material
and energy resources of the cell
• Catabolic pathways: degradative process
(hydrolysis) such as cellular respiration;
releases energy
• Anabolic pathways: building process
(dehydration synthesis) such as protein
synthesis; photosynthesis; consumes energy
Thermodynamics
• Energy (E)~ capacity to do work; Kinetic energy~ energy of motion;
Potential energy~ stored energy
• Thermodynamics~ study of E transformations
• 1st Law: conservation of energy; E transferred/transformed, not
created/destroyed
• 2nd Law: transformations increase entropy (disorder, randomness)
• Combo: quantity of E is constant, quality is not
Free energy
• Free energy: portion of system’s E that can perform work (at a
constant T) G
• Exergonic reaction: net release of free E to surroundingscatabolism
• Endergonic reaction: absorbs free E from surroundingsanabolism
Energy Coupling & ATP
• How do we get energy?
through E coupling: use
of exergonic process to
drive an endergonic one
(ATP) How do we get
energy?
• Need an energy currency• Adenosine triphosphate
• ATP tail: high negative
charge
• ATP hydrolysis: release of
free E
How does ATP store energy?
O– O– O–
O–
–OP –OP
– –OP
–
O––OP O–
O O O
O
• Each negative PO4 more difficult to add
– a lot of stored energy in each bond
• most energy stored in 3rd Pi
• 3rd Pi is hardest group to keep bonded to molecule
• Bonding of negative Pi groups is unstable
– spring-loaded
– Pi groups “pop” off easily & release energy
How does ATP transfer energy?
• ATP  ADP
– releases energy
• ∆G = -7.3 kcal/mole
• Fuel other reactions
• Phosphorylation
– released Pi can transfer
to other molecules
• destabilizing the other
molecules
– enzyme that
phosphorylates =
“kinase”
ATP / ADP cycle
Can’t store ATP
 good energy donor,
not good energy storage
ATP
cellular
respiration
7.3
kcal/mole
 too reactive
 transfers Pi too easily
 only short term energy storage
ADP + Pi
 carbohydrates & fats are
long term energy storage
A working muscle recycles over
10 million ATPs per second
Whoa!
Pass me
the glucose
(and O2)!
Enzymes
ENZYMES:Catalytic
proteins(&RNA):
-change the rate of reactions w/o
being consumed (reusable)
-reduce activation energy~the E
required to break bonds
-don’t change free energy (G)
released or required
-highly specific
• Substrate: enzyme reactant
• Active site: pocket or groove
on enzyme that binds to
substrate
Lock and Key model
• Simplistic model of enzyme
action
– substrate fits into 3-D
structure of enzyme’ active
site
• H bonds between substrate &
enzyme
– like “key fits into lock”
In biology…
Size
doesn’t matter…
Shape matters!
Induced fit model
• More accurate model of enzyme action
– 3-D structure of enzyme fits substrate
– substrate binding cause enzyme to change shape
leading to a tighter fit
• “conformational change”
• bring chemical groups in position to catalyze reaction
How Enzymes Work
•
•
•
•
•
A single enzyme molecule can
catalyze thousands or more
reactions a second
. Enzymes use a variety of
mechanisms to lower activation
energy and speed a reaction
The rate that a specific number of
enzymes converts substrates to
products depends in part on
substrate concentrations.
enzyme saturation: all enzymes are
engaged.
The only way to increase
productivity at this point is to add
more enzyme molecules.
Factors affecting enzyme function
• Enzyme concentration
– as  enzyme =  reaction rate
• more enzymes = more frequently collide with substrate
– reaction rate levels off
reaction rate
• substrate becomes limiting factor
• not all enzyme molecules can find substrate
enzyme concentration
Enzyme concentration
reaction rate
What’s
happening here?!
enzyme concentration
Substrate concentration
reaction rate
What’s
happening here?!
substrate concentration
Factors affecting enzyme function
• Substrate concentration
– as  substrate =  reaction rate
• more substrate = more frequently collide with enzyme
– reaction rate levels off
reaction rate
• all enzymes have active site engaged
• enzyme is saturated
• maximum rate of reaction
substrate concentration
Effects on Enzyme Activity
•
•
•
•
Temperature
pH
salinity
Cofactors:
inorganic, nonprotein
helpers; ex.: zinc, iron, copper
• Coenzymes:
organic helpers; ex.:
vitamins
Enzyme Inhibitors
• Irreversible (covalent); reversible
(weak bonds)
• Competitive: competes for
active site (reversible); mimics
the substrate
• Noncompetitive: bind to another
part of enzyme (allosteric site)
altering its conformation (shape);
poisons, antibiotics
Metabolic control often depends on
allosteric regulation
• In many cases, the
molecules that naturally
regulate enzyme activity
behave like reversible
noncompetitive inhibitors.
• These molecules often
bind weakly to a allosteric
site, a specific receptor on
the enzyme that is not the
active site.
• Binding by these
molecules can either
inhibit or stimulate
enzyme activity.
Metabolic pathways







A AB
BCCDDEE FF G
G
enzyme enzyme enzyme
enzyme enzyme enzyme
enzyme
1
2
3
4
5
 Chemical reactions of life
are organized in pathways

divide chemical reaction into
many small steps
 artifact of evolution
  efficiency
 intermediate branching points
  control = regulation
6
Efficiency
• Organized groups of enzymes
– enzymes are embedded in membrane
and arranged sequentially
• Link endergonic & exergonic reactions
Whoa!
All that going on
in those little
mitochondria!
Efficiency
• Organized groups of enzymes
– enzymes are embedded in membrane
and arranged sequentially
• Link endergonic & exergonic reactions
Whoa!
All that going on
in those little
mitochondria!
Feedback Inhibition
• One of the common
methods of metabolic
control is feedback
inhibition in which a
metabolic pathway is
turned off by its end
product.
• The end product acts as an
inhibitor of an enzyme in
the pathway.
• When the product is
abundant the pathway is
turned off, when rare the
pathway is active
Feedback inhibition
threonine
• Example
– synthesis of amino acid,
isoleucine from amino
acid, threonine
– isoleucine becomes the
allosteric inhibitor of the
first step in the pathway
• as product accumulates it
collides with enzyme more
often than substrate does
isoleucine
Cooperativity
• Substrate acts as an activator
– substrate causes conformational
change in enzyme
• induced fit
– favors binding of substrate at 2nd site
– makes enzyme more active & effective
• hemoglobin
Hemoglobin
 4 polypeptide chains
 can bind 4 O2;
 1st O2 binds
 now easier for other 3
O2 to bind
Don’t be inhibited!
Ask Questions!
2007-2008