Download Keshara Senanayake Ms.Reep AP BIOLOGY Chapter 6

Keshara Senanayake
Ms.Reep
AP BIOLOGY Chapter 6: Introduction
to Metabolism
 In living cell is a chemical factory w/ thousands of reactions
>process called cellular respiration drives the cellular economy by extracting the energy stored in sugars
and other fuels (cells apply this to perform work)
 the totality of an organisms’ chemical reactions is called metabolism  is an emergent properties of life
that arises from orderly interactions between molecules
 in a metabolic pathways, a specific molecule is altered in a series of defined steps, resulting in a product
 each step of the bath way is catalyzed by a specific enzyme
Starting molecule A - -enzyme 1/Reaction 1 - - -> B- - enzyme 2/reaction 2 - - - > C - - enzyme 3/reaction
3 - -> D product
 mechanisms that regulate enzymes balance metabolic supply and demand
 metabolism manages the material and energy resources of the cell
>some metabolic pathways release energy by breaking down of complex molecules  called catabolic
pathways (or breakdown pathways)  cellular respiration is an example  energy stored in the organic
molecules broken down becomes available to do work of the cell
 Anabolic pathways consume energy to build complicated molecules from simpler ones (called
biosynthetic pathways)
>Catabolic and anabolic pathways are “downhill” and “uphill” avenues of the metabolic landscape 
energy released from downhill catabolic pathways can be stored to drive the uphill reactions of anabolic
pathways
 bioenergetics is the study of how energy flows through living organism
 Energy is the capacity to cause change  can be used to do work (energy is the ability to rearrange a
collection of matter)
>energy exists in a variety of forms and life depends on ability of cells to transform energy to one form to
another
>energy associated with the relative motion of objects is called kinetic energy (moving objects can form
work by imparting motion to other matter)  thermal energy is kinetic energy associated with the random
movement of atoms or molecules  thermal energy in transfer from one object to another is called heat
objects not moving have energy  energy that is not kinetic is potential energy; it is energy that matter
possesses because of its location or structure  molecules posses energy due to arrangement of electrons
in bonds between atoms
 chemical energy is the potential energy available for release in a chemical reaction  catabolic
pathways release energy by breaking down complex molecules which are high in chemical energy and
during catabolic reactions some bonds are broken and others formed RELEASING energy and resulting in
lower-energy breakdown products
 organisms are energy transformers
 the study for energy transformations in matter is called thermodynamics
>system is matter under study  everything outside the system is terms the surroundings
>an isolated system is unable to exchange either energy or matter w/ surroundings (while an open system
can) (organism are open systems)
 According to the first law of thermodynamics the energy of the universe is constant  energy can be
transferred or transformed but it cannot be created (known as the principal of conservation of energy)
>during every energy transfer transformation some energy is converted into thermal energy and released as
heat (becoming unavailable to do work)  in body fraction of chemical energy from food is transformed to
motion (rest is lost as heat)
 system can use thermal energy for work when there is a temperature difference that results in the
thermal energy flowing from a warmer location to a cooler one (if temp is = like in living system the heat
will simply warm the organism’s body)
 loss of useable energy = universe is more disordered  quantified as entropy (measure of
disorder/randomness)  more random = greater entropy
 second law of thermodynamics: every energy transfer or transformation increases the entropy of the
universe
>even if order increase locally total randomization increases
>entropy helps us understand why certain process occur without energy (it must increase entropy of
universe)  process can occur without energy is called a spontaneous process  it means the process is
energetically favorable  a process that can’t occur on its own is no spontaneous (happens w/ energy to
system)
>can state 2nd law also by: for a process to occur spontaneously it must increase the entropy of the universe
 living systems increase entropy of surroundings
>while cells make ordered structures from less organized starting material and at the organism level
complex order red structures result from simpler starting material the organism also takes in organized
forms of material/energy from surroundings and makes them less ordered (obtain starch/other complex
molecules  catabolic pathways break them down and animal releases CO2 and H2O -- contain less
chemical energy than food  accounting by heat generated by metbalism0  large-scale energy flows into
ecosystems in form of light and exits via heat
>from early history complex organism evolved from simpler ancestors  this increase in organization does
NOT violated second law  entropy of system may decrease as long as total entropy of universe increases
 Willard Gibbs helped bring out Gibbs Free energy (symbol = G)  free energy is the portion of a
system’s energy that can perform work when temperatures and pressures are uniform throughout the
system when system changes (as in chemical reaction) the change in free energy can be calculated by:
(delta G = delta H - T(delta S)
Delta H = system’s enthalpy (total energy in a biological system)
Delta S = change in system’s entropy
T = absolute temperature in Kelvin (K)
Delta F can be used to predict is a particular process is energetically favorable  reactions with negative
delta G occur without energy so delta G can tell us about spontaneity
>important for metabolism (to see which occur spontaneously)  biologist focus on the change in free
energy in chemicals reactions of life (think of delta G are the difference between the free energy for final
and initial state) delta G = Gfinal - Ginitial
 breakdown of glucose into CO2 + H2O is a delta G of -686 kcal
 reaction with a negative delta G the system must lose free energy during the change from initial to final
state  because of less free energy the system in its final state is less likely to change and is therefore more
stable than before
>free energy can be a measure of a system’s instability (tendency to move to a more stable state) 
unstable (higher G) tend to change so they can become more stable (lower G)
 maximum stability = equilibrium
>at equilibrium forward and reverse reactions occur at the same rate (no net change in relative
concentration of product/reactants)  system at equilibrium G is at its lowest possible values in that system
 any change from the equilibrium position will have a positive delta G and will not be spontaneous
(system never spontaneously move from equilibrium)  since as system at equilibrium can’t change
spontaneous it can do not work  a process is spontaneous and can perform work only when it is moving
towards equilibrium
 based on free energy chemical reactions can be considered exergonic or endogenous
>exergonic reaction proceeds with a net release of free energy (G decreases)
>delta G is for exergonic reactions (so these occur spontaneously  in this case it means it is energetically
favorable)
>magnitude of delta G for an exergonic reaction represents the maximum amount of work the reaction can
perform (some free energy is release and can’t do work)  greater decrease in free energy = more work
can be done
 breaking of bonds does not release energy (its requires it)
>“energy stored in bonds” is shorthand for potential energy that can be released when new bonds are
formed after the original bonds break as long as the products are lower free energy than the reactants
 An endergonic reaction is one that absorbs free energy from its surroundings
>stores free energy (G increases and is positive)  are nonspontaneous and the magnitude of delta G is the
quantity of energy required to drive the reaction
>if process of exergonic the reverse is endergonic of that reaction
 reactions in an isolated system eventually reach equilibrium and can then do no work (chemical
reactions of metabolism are reversible and will also reach equilibrium if occurring in isolation)  since
equilibrium = no work a cell w/ metabolic equilibrium is dead  metabolism as a whole is never at
equilibrium is one of the defining features of life
 constant flow of molecules in/out of a cell keeps metabolic pathways from reaching equilibrium (cell
continuous to do work through its life)
>some of the reversible reactions of respiration are pulled in one direction (keep it from equilibrium  key
to maintaining equilibrium is that product of reaction does not accumulate but becomes reactant in next
step (and at last waste products are expelled from cell)  kept going by huge energy difference between
glucose and oxygen at the top of “hill” and CO2/H2O “downhill” end
>shows how it’s important for an organism to be an open system (sunlight provides free energy for an
ecosystem’s plants/photosynthetic organism)
 Cell does (3) main kinds of work
>(1) Chemical work  pushing of endergonic reactions that would not occur spontaneously (synthesis of
polymers from monomers)
>(2) Transport work  pumping of substances across membrane against the direction of spontaneous
movement
>(3) Mechanical work  like beating of cilia, contraction of muscle cells, and movement of chromosomes
during cellular reproduction
>key feature of cell managing energy resources to do this work is via energy coupling  use of exergonic
process to drive a endergonic one
>ATP is responsible for mediating most energy coupling in cells (acts are immediate source of energy in
many cases)
 ATP (adenosine troposphere) contains sugar ribose w/ nitrogenous base adenine and a chain of (3)
phosphate groups bonded to it
>other then its role in energy coupling ATP is also one of the nucleoside triphosphates used to make RNA
 bond between phosphate group of ATP is broken via hydrolysis
>when terminal phosphate Is broken inorganic phosphate [HOPO3^2-  abbreviated (P)i] leaves ATP
>adenosine troposphere becomes adenosine diphosphate (ADP)  is exergonic (releases 7.3 kcal of energy
per mole of ATP hydrolyzed)
>this is under standard conditions (STC)  in cells STC doesn’t happen (concentration differ from 1M) (in
real life 78% greater energy is released by ATP hydrolysis under STC)
>since hydrolysis release energy because note that the reactants (ATP and water) are high energy
RELATIVE to the energy of the products (ADP and (P)i)  release of energy during hydrolysis of ATP
comes from the chemical change to a state of lower free energy not from phosphate bonds themselves
>ATP is useful to cell because the losing phosphate group gives greater energy than most other cells
>WHY SO MUCH ENERGY?  three phosphates are negatively changed (mutual repulsion contributes to
instability of this region of ATP)  triphopshate tail of ATP is like a compressed spring
 if ATP is hydrolyzed in test tube is merely releases heat to surrounding  cell’s proteins harness the
energy released during ATP hydrolysis in many ways to perform (3) types of cellular work (chemical,
transport, and mechanical)
>w/ help of specific enzymes cell can use energy released by ATP hydrolysis to directly drive chemical
reaction that by itself are endergonic (if delta G of endergonic reaction is less than amount released by ATP
hydrolysis than the reactions can be coupled so overall will be exergonic)  involved phosphorylation
(transfer of a phosphate group from ATP to some other molecules)  recent w/ phosphate group covalently
bonded to it is called a phosphorylated intermediate
>key to coupling exergonic/endergonic reactions is the formation of phosphorylated intermediate (which is
more reactable (less stable) than original unphosphorylated molecule)
 transport/mechanical work in cell is nearly always powered by the hydrolysis of ATP
>in this case ATP hydrolysis causes a change in protein’s shape and its ability to bind to another molecule
(can occur via phosphorylated intermediate)
>in most instances mechanical work involved motor proteins “walking” along cytosketal elements 
textbook shows how a cycle occurs in which ATP is first bound no covalently to the motor protein then
ATP is hydrolyzed released ADP and (P)i  another ATP can then bind and at each stage the motor
protein changes its shape and ability to bind to the cytoskeleton resulting in movement of the protein along
the cytoskeleton track
>phosphorylation and dephosphorylation also promote crucial protein shape changes during cell signaling
>an organism at work uses ATP continuously but ATP is a renewable resource that can be regenerated by
the addition of phosphate to ADP
>free energy to phosphor late ADP is via exergonic breakdown reaction (catabolic) in cell
>shutting of inorganic phosphate + energy is ATP cycle  couples exergonic processes to endergonic ones
 very quick
>the regeneration of ATP from ADP + (P)i is endergonic
>since ATP formation if not spontaneous free energy is spent to make it occur  catabolic pathways (like
cellular respiration) give energy for endergonic process of making ATP (ATP cycle is like a revolving door
through which energy passes during its transfer from catabolic to anabolic pathways)
spontaneous reactions might occur without any energy but can occur slowly
>an enzyme is a macromolecule that acts as a catalyst  chemical agent that speeds up a reaction without
being consumed by the reaction  without enzymes any reactions would take a long time
 every chemical reaction involved breaking/forming bonds
>changing one molecules into another generally involves contorting the starting molecule into a highly
unstable state before the reaction can proceed  to reach the contorted state where bonds can change
reactant molecules must absorb energy from their surroundings
>when new bonds of the product form energy is released as heat and molecules return to stable shapes w/
lower energy than contorted state
>initial energy to start reaction/energy required to contort the reactant molecules so bonds can break is
known as free energy of activation (activation energy) Ea
>imagine as energy needed to push the reactants to the top of an energy barrier (uphill) so a “downhill” part
of reaction can begin
>Ea is often supplied by heat (in form of thermal energy) that reactant molecules absorb from surroundings
 this accelerates reactant molecules so they collide more often (and forcefully)  agitates the atoms
within the molecules making the breakage of bonds more likely  when molecules have absorbed enough
to break bonds the reactants are in an unstable condition known as the transition state
AB + CD  AC + BD
(reactants) (products)
Reactants AB and CD must absorb enough energy from surroundings to reach unstable transition state
where bonds break
After bonds have broken new bonds form releasing energy to surroundings
A ~ B / C ~D
(transition state)
/
|
\
/
Ea
\
---(reactants/
|
\ products) A - C / B-D (delta D < 0)
A-B / C-D
>activation of reactant = uphill of the graph  free energy content of the reactant molecules are increasing
>at summit (energy = Ea has been absorbed) reactants are in transition state  are activated and bonds can
be broken
>as atoms settle to new (stable) bonding arrangements energy is released to surroundings (downhill part of
curve)  overall decrease in in free energy means that Ea is repaid with interest as formation of new bonds
release more energy than was invested in the breaking of old bonds
 Above reaction is exergonic/occurs spontaneously (delta G < 0)  Ea barrier determines rate of
reaction
>reactants must absorb enough energy to reach top of Ea barrier before reaction can occur
(like spark plug fire in an engine to give enough heat to give enough energy to overcome Ea for the
spontaneous reaction to occur [reaction of oxygen and gasoline IS spontaneous but has a high Ea)
Proteins/DNA/other molecules decompose naturally but persist because at temperatures typical for
cell few molecules can make it over the Ea
>barrier for selected reactions must occasionally be surmounted for cells to carry out the processes
needed for life
Heat speeds a reaction by allowing reactants to attain transition state more often (this solution
would be inappropriate for biological reactions because high temp denatures proteins/kills cells
and heat speeds up ALL reactions not just the ones needed)  organisms use catalyses to speed
up reactions
Enzymes catalyze a reaction by lowering Ea and enabling reactant molecules to absorb enough
energy to reaction transition state w/ moderate temperatures (enzymes DO not change delta G and
cannot make an endergonic reaction exergonic
.enzymes can hasten reactions that would occur anyways but makes it possible for cells to make
DYNAMIC equilibrium routing chemicals through cell’s metabolic pathways
>enzymes are specific for reactions they can catalyze
Substrate is the reactant enzymes act on
Enzymes bind to its substrate(s) forming an enzyme-substrate complex

when enzyme and substrate are joined the catalytic action of the enzyme converts substrate to the
product(s)
Seen here:
 Enzyme +
 Substrate(s)
Enzyme < - ->
substrate complex
Enzyme +
< - ->
product(s)
Note most enzyme names end in –ase
Reaction catalyzed by each enzyme is very specific; an enzyme can recognize its specific substrate
even among related compounds
>molecular recognization is due to the unique 3D shape of proteins (like enzymes)  specificity
of enzymes come from shape (consequence of its amino acid sequence_
active site is a restricted region of the enzyme molecule actively binds to the substrate
>usually a pocket/groove on surface of enzyme where catalysis occurs  usually formed by a few
amino acids w/ rest of the protein molecule giving framework that gives configuration of the
active site  specificity of an enzyme is contributed to complementary fit between the shape of its
active site and the shape of the substrate
 enzyme is not a stiff structure  seems to “dance” w/ different shapes in dynamic equilibrium (slight
difference in free energy in each pose) shape that best fit does not always have lowest free energy but the
short time that enzyme takes a shape a substrate can bind  as substrate enters active site the enzymes
shape changes slightly due to interactions w/ substrate chemical groups and chemical groups on side chains
of amino acids that form the active side  shape change makes active site more snugly  induced fit
brings chemical groups of the active site into positions that enhance their ability to catalyze chemical
reactions
Substrate is held in the active site by “weak” interactions (hydrogen/ionic bonds)
>R groups of a few amino acids that make up the active site catalyze the conversion of substrate to
product (and products depart from active site)  enzyme is then free to take another substrate
molecule into its active site  cycle happens fast  enzymes merge from their reactions in
original form (so very small amount of enzymes can have a huge metabolic impact by functi0ning
over and over again in catalytic cycles
Most metabolic reactions are reversible and enzymes can catalyze forward or reverse reaction
depending on which direction has a negative delta G  depends mainly on relative concentrations
of reactants and products  net effect is always in direction of equilibrium
>enzymes use a variety of mechanism that lower Ea and speed up reactions (1) in reactions
involving 2+ reactants the active site provides a template on which substrate can come together in
the proper orientation (for reaction to occur)  (2) active site of an enzyme clutches bound
substrates the enzyme may stretch the substrate molecules toward transition state form stressing
and bending critical chemical bonds that must be broken during the reaction
Since Ea is proportional to the difficulty of breaking the bonds distorting substrate helps it
approach the transition state/reduce amount of free energy that must be absorbed to achieve that
state
(3) active site may provide a microenvironment more conducive to a particular type of reaction
than the solution itself would be without the enzyme (i.e. active site has acidic R groups (pocket
of low pH) the acidic amino acid may facilitate H+ transfer to substrate as key step in catalyzing
the reaction
(4) mechanism of catalysis is the direct participation of the active site in the chemical reaction
process may involve brief covalent bonding between the substrate and the side chain of an
amino acid o the enzyme
Subsequent step of reaction restore the side chain to original state so that active site is the same
after the reaction it was before
 rate at which a particular amount of enzyme converts substrates to products is partly a function of
the initial concentration of substrate  more substrate = more frequently they access the active
sites of the enzyme molecules
>there is a limit to how fast the reaction can be pushed by adding more substrate to a fix
concentration (at some point the concentration of substrate will be high enough that all enzyme
molecules have their active sites engaged)  as soon as product exits active site another substrate
enters  at this substrate concentration the enzyme is saturated and rate of reaction is determined
by the speed at which the active site converts substrate to products  when enzyme population is
saturated only way to increase rate of formation is by adding more enzymes (cells does this)
 more efficiently an enzyme functions is affected by general environmental factors (temp/ph) and by
chemicals
3D shape of proteins are sensitive to their environment  each enzyme works better under some
optimal conditions (these conditions favor the most active shape for enzyme molecule)
 temp/pH are environmental factors important in the activity of an enzyme (up to a point rate of
enzyme reaction increases with temperature because substrate collide w/ active sites more but
above that temp the speed of enzymatic reaction stops  thermal agitation disrupts the
hydrogen/ionic bonds and weaken interactions that stabilize the active shape of the enzyme (and
then denatures)
 each enzyme has an optimal temperature at which reaction rate is greatest (most human enzymes
have optimal temperatures about 35-40 Celsius)  also an optimal pH (usually 6-8) (pepsin ~ 2
and trypsin ~8)
 non protein helpers for catalytic activity are cofactors
 cofactors of enzymes that are inorganic = (metal atoms) in ionic form
 cofactors of enzymes that are organic = coenzymes (most vitamins)
>function in various ways but they perform crucial chemical functions in catalysis
 certain chemicals selectively inhibit the action of specific enzymes
>if the inhibitor attaches to the enzyme by covalent bonds inhibition is usually irreversible
>most enzyme inhibitors bind w/ weak interactions and are reversible  they resemble the normal
substrate molecule and compete for admission into the active site
>these mimics = competitive inhibitors  reduce the productivity of enzymes by blocking substrates
from entering active sites  this inhibition can be overcome by increasing concentration of
substrate so that active sites become available more substrate molecules than inhibitor molecules
are around to gain entry to the sites
 noncompetitive inhibitors do not directly compete w/ substrate to bind to the enzyme at the active
site instead they impede enzymatic reactions by binding to another part of the enzyme  this
interaction causes the enzyme molecule to change its shape in a way that the active site becomes
less effective at catalyzing the conversion of substrate to product
>many antibiotics are inhibitors of specific enzymes in bacteria
>molecules naturally present in the cell often regulate enzyme activity by acting as inhibitors 
selective inhibition is essential to the control of cellular metabolism
>permanent change in a gene is a mutation  can result in a protein w/ one or more changed amino
acids  in case of enzyme if the changed amino acids are in the active site/crucial region the
altered enzyme might have a novel activity or might bind to different substrate  under
environmental conditions where new function benefits organism natural selection would tend to
favor the mutated form of the gene causing to persist
 cell needs to regulate its metabolic pathways by controlling various enzymes  does this either by
switching on/off the genes that encode specific enzymes or by regulating the activity of enzymes
once they are made
 the molecules that regulate enzyme activity in a cell behave like reversible noncompetitive
inhibitors  these regulatory molecules change an enzyme’s shape and the functioning of the its
active site by binding to a site elsewhere by no covalent interactions
 allosteric regulation is the term to describe any case in which a protein’s function at one site is
affected by the binding of a regulatory molecule to a separate sit  may result either inhibition or
stimulation of an enzyme’s activity
 most enzymes that are allosterically regulated are constructed from 2+ subunits composed of a
polypeptide chain w/ its own active site  complex oscillates between two different shapes  one
catalytically active and the other inactive
>in the simplest kind of allotter regulation an activating or inhibiting regulatory molecule binds to a
regulatory site (allosteric site)  where subunits join
>binding of an activator  to a regulatory site stabilizes the shape that has functional active sites 
binding of an inhibitor stabilizes the inactive form of the enzyme
>subunits of an allotter enzyme fit together in such a way that a shape change in one subunit is
transmitted to all others  via this interaction of subunit’s a single activator or inhibitor molecule
that binds to one regulatory site will affect the active sites of all subunits
>fluctuating concentrations of regulators can cause a sophisticated patter of response in activity of
cellular enzymes
>products of ATP hydrolysis (ADP (P)i) play a complex role in balancing the flow of traffic between
anabolic and catabolic pathways by their effects on key enzymes
>ATP binds to several catabolic enzymes allosterically lowering their affinity for substrate and
thus inhibiting their activity  ADP functions as an activator of the same enzyme
>logical because catabolism functions in regenerating ATP  is ATP production lags ADP
accumulates and activates the enzymes that speed up catabolism producing more ATP  if ATP
supply exceeds demand then catabolism slows down as ATP molecules accumulate and bind to
the same enzyme inhibiting them
>ATP, ADP, and other related molecules also affect key enzymes in anabolic pathways.  via this
allotter enzymes control the rates of important reactions in both sorts of metabolic pathways
 another kind of allotter activation, a substrate molecule binding to one active site in a multisubunit
enzymes triggers a shape change in all subunits thus increasing catalytic activity at the other active
sites  called cooperativity  mechanism amplifies the response of enzymes to substrate
>one substrate molecule primes an enzyme to act on additional substrate molecules more readily
>cooperativity is considered “allotter regulation” because binding of one substrate to one active site
affects catalysis in another active site (binding of one substrate molecule to active site of one
subunit locks all subunits in active conformation)
 vertebrate oxygen transport protein (not an enzyme)  classic studies of cooperative binding in this
protein have elucidated the principal of cooperativity. Hemoglobin is made up of four subunits,
each of which has an oxygen-binding site  binding of an oxygen molecule to one binding site
increases the affinity for oxygen of the remaining binding sites  thus where oxygen is at high
levels hemoglobin affinity of oxygen increases as more binding sites are filled (in oxygen
deprived tissues the release of oxygen molecules decrease the oxygen affinity of other binding
sites)  cooperativity works in similar ways in multisubunit enzymes
 when ATP allosterically inhibits an enzyme in ATP-generating pathways the result is feedback
inhibition  common mode of metabolic control
>a metabolic pathway is switched off by the inhibitory binding of its end product to an enzyme that
acts early in the pathway  feedback inhibition prevents the cell from wasting chemical
resources by making no more of a product than is necessary
 cell is compartmentalized and cellular structures help bring order to metabolic pathways
>in some cases team of enzymes for several steps of metabolic pathway is assembled into multienzyme complex
>arrangement facilitates the sequence of reactions w/ the product from the first enzyme becoming
the substrate for an adjacent enzyme in the complex until the end product is released  some
enzyme and enzyme complexes have fixed locations within the cell and act as structural
components of particular membranes  others are in solution within particular membraneenclosed eukaryotic organelles each w/ its own internal chemical environment