Chapter 8 INTRODUCTION TO METABOLISM

Summary of Chapter 8, BIOLOGY, 9

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ED Campbell, by J.B. ee!e et al. "#$$.
METABOLISM, ENERGY AND LIFE
Metabolism from the Greek metabole = change
The totality of the chemical reactions taking place in an organism.
Metabolism is concerned with managing the materials and energy available to the cell.
The chemistry of life is or!"i#e$ i"to chemic!l %!th&!ys'
Metabolic reactions require energy transformations.
Metabolism allows the organism to move grow heal reproduce etc.
A"!(olism refers to metabolic reactions that synthesi!e comple" organic molecules from
simpler ones. These reactions consume energy to build more comple" molecules.
#rom the Greek$ a%a$ back up and bolo&$ to lump or build e.g. build up.
C!t!(olism is the metabolic reactions in which comple" molecules are broken down into
simpler ones. They release energy.
#rom the Greek$ !ata$ down dissolution and bolo&$ to lump or build e.g. to break down.
Or!"isms tr!"sform e"ery'
E"ery is the capacity to do work.
)or* is any change in the state or motion of an ob%ect& to move matter against opposing forces
such as gravity and friction.
'nergy can change form. The work of life depends on the ability of cells to transform energy
from one type into another.
+i"etic e"ery is the energy of motion& it is a measure of the ,elocity !"$ m!ss of an ob%ect.
'. g. if two gases have the same average kinetic energy (temperature) the gas with the
smaller molecules will be moving on the average faster than the gas with more massive
molecules.
Temperature is the measured !,er!e *i"etic e"ery of a substance. *t is measured in
degrees Celsius C+.
Therm!l e"ery is the kinetic energy of system due to the movement of the atoms molecules
and other particles that form the system.
-ote"ti!l e"ery is stored energy. *t is due to its location or structure.
.e!t is thermal energy that can be transferred between ob%ects of different temperature. This
transmitted energy is stored as kinetic energy in the translational movement of atoms and
molecules the rotation of molecules and the vibration associated with the interatomic bonds of
molecules. *t is the total amount of kinetic energy in a substance that its bulk is not moving.
Chemic!l e"ery is the potential energy stored in the bonds of molecules. *t is particularly
important in living systems.
Chemical energy can be transformed into kinetic energy.
,uring chemical reactions the atoms of molecules become rearranged and some chemical
energy (potential energy stored in the molecules) is converted into kinetic energy.
Cellular respiration and other catabolic pathways unleash energy stored in carbohydrates to
make energy available for cellular work.
-rganisms are energy transformers.
T.ERMODYNAMICS
Thermo$y"!mics is the study of energy and its transformations.
System is the ob%ect being studied in thermodynamics.
S/rro/"$i" is the rest of the universe other than the system.
Close$ systems do not e"change matter or energy with its surroundings.
O%e" systems e"change matter and.or energy with the surroundings.
/. First l!& of thermo$y"!mics.
'nergy of the universe is constant.
'nergy can be transferred and transformed but it cannot be created or destroyed.
'nergy0mass cannot be created nor destroyed.
This law is also known as the -ri"ci%le of Co"ser,!tio" of E"ery or M!tter.
1. Seco"$ l!& of thermo$y"!mics.
The entropy of the universe increases with every transfer or transformation of energy.
E"tro%y is a measure of the disorder or randomness of a system.
'very energy transfer or transformation increases the disorder in the universe. *t
increases the entropy of the universe.
2lso known as the L!& of I"cre!se$ E"tro%y.
3hen energy is converted from one form to another some of the usable energy is converted to
heat and is dispersed in the surroundings.
2t every step of energy transformation there is a loss of energy capable to do work.
4o one process that requires energy conversion is /556 efficient. 7ome energy is always lost
in the form of heat the random motion of molecules.
'ntropy or disorder in a closed system tends to increase spontaneously over time.
Certain processes in the universe occur without the input of energy. They are called
s%o"t!"eo/s %rocesses.
7pontaneous processes increase the entropy of the universe.
,o not require the input of energy.
They are not necessarily quick or fast. 2n e"plosion is fast& rusting of a car is slow.
'ntropy is a measure of the inability of a system to do work or dispersal energy.
8eat is the energy of random molecular motion. Molecules and atoms change their kinetic
energy because heat flows in or out of them. 8eat is 9energy in transit.:
Bioloic!l or$er !"$ $isor$er
;iving systems are orderly and require energy in order to maintain their orderliness.
7imple molecules are ordered into comple" ones e.g. amino acids are organi!ed into
polypeptides (anabolic reactions).
-rganisms take comple" molecules and break them down into simpler ones e.g. start is
broken down into glucose (catabolic reactions).
'nergy flows into ecosystems in the form of light and leaves in the form of heat after a series of
transformations within the ecosystem.
-rganisms increase the entropy of the universe by releasing small molecules and heat into their
surroundings. These molecules and heat energy come from the more organi!ed molecules of
food$ starch proteins etc.
The evolution of biological order is perfectly consistent with the laws of thermodynamics.
FREE ENERGY
The free0energy change of a reaction tells us whether or not the reaction occurs spontaneously.
Free e"ery is the portion of a system<s energy that can perform work when temperature and
pressure are uniform throughout the system like in a living cell.
#ree energy is the energy available to work.
7pontaneous processes decrease the free energy in the system.
7ome processes occur spontaneously. S%o"t!"eo/s processes occur on their own e. g. water
runs down hill.
3hen a spontaneous process occurs the stability of the system increases.
Systems !l&!ys te"$ to&!r$ re!ter st!(ility unless prevented from doing so e. g. a dam
prevents water from running down hill.
=rocesses that do not occur on their own are "o"s%o"t!"eo/s. They occur only if energy is
added to the system.
The living cell is a system.
#ree energy (G) has two components$ the total energy or e"th!l%y of the system (8) and its
e"tro%y (7).
T is the absolute temperature of the system given in degrees >elvin > = 1?@ A
o
C
'nthalpy (8) entropy (7) and free energy (G) are related by the equation G 0 . 1 TS.
The following equation is used to e"press what happens in a chemical reaction G 0 . 1 TS.
The Greek letter symboli!es change'
4o reaction can take placeB
without a decrease in enthalpy . must be negative (the system gives up energy
and . decreases).
an increase in entropy TS must be positive (the system becomes more chaotic and
S increases).
or both.
4otice that an increase in temperature increases the entropy component of the system.
The total energy of the system minus its entropy leaves the energy available to do work G.
=rocesses that have a positive or !ero CG are never spontaneous.
E2!m%le -ro(lem3
Calculate the entropy of the surroundings for the following two reactions.
a.) C188(g) A D -1(g) E @ C-1(g) A F81-(g) C8 = 015FD kG
b.) 81-(l) E 81-(g) C8 = AFF kG
Sol/tio"
The change in entropy of the surroundings after a chemical reaction at constant pressure and
temperature can be e"pressed by the formula
C7surr = 0C8.T
where
C7surr is the change in entropy of the surroundings
0C8 is heat of reaction
T = 2bsolute Temperature in >elvin
Re!ctio" !
C7surr = 0C8.T
C7surr = 0(015FD kG).(1D A 1?@) HHIemember to convert JC to >HH
C7surr = 15FD kG.1K8 >
C7surr = L.8L kG.> or L8L5 G.>
4ote the increase in the surrounding entropy since the reaction was e"othermic.
,o the calculation for Ieaction b. Me careful with the A and N signs.
Free e"ery, st!(ility !"$ e4/ili(ri/m
7ystems that occur spontaneously to a more stable state tend to have high energy (8) low
entropy (7) or both.
G is a measure of the systems instability therefore...
*n any spontaneous process free energy decreases.
The total amount of free energy cannot be measured but changes ( delta) in free energy can
be measured.
G 0 G fi"!l st!te 1 G st!rti" st!te
G 5 6, free energy change here has a negative value because it represents a loss of energy
from the system.
The greater the decrease in free energy the greater the amount of work the spontaneous
process can perform.
=rocesses that decrease the systemOs free energy are spontaneous& and processes that have a
positive or !ero G are never spontaneous.
2 system or chemical reaction reaches equilibrium G 0 6, because there is no net change in
the energy of the system. 'nergy is neither being lost nor gained by the system. This represents
the state of ma"imum stability for that system.
7ystems at equilibrium can do no work. See f'(. 8.), pa(e $*+.
Met!(olic $ise4/ili(ri/m
E2ero"ic reactions release energy and are spontaneous 1G. #ree energy decreases& PG is
negative.
CL8/1-L A L-1 LC-1 A L 81- G = 0 L8L kcal.mol (or 018?5 kG.mol)
*n this reaction for every mole of glucose (/85 g) L8L kcal were released and the products had
as a result a total of L8L kcal less than the reactants.
There is an increase in free energy in e"$ero"ic reactions. These reactions store energy& PG
is positive.
The energy absorbed during the reaction must be supplied by the surroundings.
*f a reaction is e"ergonic its reverse is endergonic. Therefore
LC-1 A L 81- A solar energy CL8/1-L A L-1 G = AL8L kcal.mol (or A18?5 kG.mol)
This reaction will never happen spontaneously by itself. The organism takes energy from the
environment.
E4/ili(ri/m !"$ met!(olism
Metabolic reactions are reversible and will reach equilibrium if they occur in a closed system.
2 cell at equilibrium is a dead cell.
Metabolic reactions in leaving cells occur in an open system& living cells are open systems$ e.g.
food is going in from outside and wastes are being e"creted to the surroundings. See f'(. 8.+.
C!t!(olic %!th&!ys release energy in a series of steps in which the product of one reaction
become the reactants of the ne"t reaction. See f'(. 8.+!.
These reactions are reversible and could reach equilibrium but they are prevented from doing
so by the constant supply of initial reactants and the use of the products in other reactions and
the eventual e"cretion of the final products (waste) to the surroundings.
2 key feature of bioenergetics is energy coupling$ the free energy required to drive an
endergonic reaction may be supplied by coupling it to an e"ergonic reaction.
AT- !"$ cell/l!r &or*
2T= powers the cell by coupling e"ergonic and endergonic reactions.
The cell does three main kinds of work$
/. Mechanical work$ muscle contraction beating of flagella etc.
1. Transport work$ !cti,e tr!"s%ort across membranes against the concentration gradient.
@. Chemical work$ supplying energy to endergonic reactions that would not occur
spontaneously like polymeri!ation of proteins.
Str/ct/re of AT-
The structure resembles a nucleotide used in I42.
The nitrogenous base !$e"i"e bonded to a ri(ose sugar which in turn is bonded to a chain of
three %hos%h!te groups& only one phosphate is attached to the ribose. See f'(. 8.8 o% p. $*9.
The phosphate bonds are referred to as high0energy bonds and can be broken by hydrolysis
thus releasing energy.
8igh0energy bonds imply strong bonds but in reality 2T= phosphate bonds are relatively weak
compared to the strong bonds of other organic molecules.
8ydrolysis of 2T=$ AT- 7 .8O 9 AD- 7 -i :G 0 1;'< *c!l=mole >1<? *@=moleA
?.@ kcal.mole are released in the laboratory under standard conditions (7T=$ 1DJC and / atm).
Cells have an environment different from standard conditions and the CG is 0/@ kcal..mole or
?86 higher than 7T= conditions.
7tandard temperature and pressure (7T=)$ temperature of 5 JC (1?@./D >) and pressure
of / atm (defined as /5/.@1D k=a).
7tandard ambient temperature and pressure (72T=)$ temperature of 1D JC (1K8./D >)
and pressure of /55 k=a.
=i stands for inorganic phosphate.
The chain of three phosphate group contains many several negative charges that repel one
another and weakens the phosphate bonds allowing them to break away relatively easily.
2T= is the link between e"ergonic catabolic reactions and endergonic anabolic reactions.
Co/%le$ re!ctio"s$ *M=-IT24T T- Q4,'I7T24,RR
The substance that receives a phosphate group is said to by %hos%horyl!te$.
*n the cell the hy$rolysis of AT- (e"ergonic reaction) is coupled to the phosphorylation
of one of the reactants in an endergonic reaction. The phosphorylated molecule
becomes reactive less stable than the original non0phosphorylated molecules.
,uring the reaction of the %hos%horyl!te$ i"terme$i!te with the other reactant the
phosphate group is displaced by the second reactant. This second process is
endergonic but absorbs less energy than the one released by the hydrolysis of 2T=.
2ll cellular work depends on the transfer of phosphate groups to reactants of endergonic
reactions.
2T= is regenerated during the 2T= cycle$
2,= A =i E 2T= CG = A?.@ kcal.mole (A@/ kG.mole)
This process is endergonic and the energy comes from the catabolic occurring during cell/l!r
res%ir!tio".
See f'(. 8.$$.
ENBYMES
7pontaneous reactions can occur very slowly.
'n!ymes are catalysts that speed up metabolic reactions by lowering the energy barrier.
Catalysts are capable of changing the rate of a reaction but are not consumed during the
reaction. Catalysts do not form products during chemical reactions.
'n!ymes are proteins that act as catalysts.
'n!yme names usually end in 1!se.
Chemical reactions involve the breaking and forming of chemical bonds.
The breaking of bonds require energy an endergonic process.
The formation of bonds is an e"ergonic process.
See a%'mat'o%$ http$..www.stolaf.edu.people.giannini.biological615anamations.html
The initial amount of energy that is absorbed in order to break bonds is called !cti,!tio"
e"ery or free energy of activation.
Molecules must absorb enough energy to become unstable and capable of reacting. Qnstable
molecules are reactive.
2bsorption of thermal energy increases the speed of molecules causing more and stronger
collisions capable of causing Smolecular damageS and the breaking of bonds.
'"ergonic reactions release more energy during bond formation than the amount absorbed
during the activation process.
'ndergonic reactions absorb more energy during activation than they release during bond
formation.
,uring the reaction intermediate molecules high in energy are formed temporarily before they
break into the products. 'ach of these intermediates is called !cti,!te$ com%le2.
The activation energy creates a barrier against the spontaneous decomposition of proteins
nucleic acids and other essential molecules.
The cellular environment does not provide enough energy for these organic molecules to
decompose spontaneously following the laws of thermodynamics$ tendency toward less
enthalpy and greater entropy.
2n en!yme speed up the reaction by lowering the activation energy requirement so more
molecules can surmount the barrier and react to form products in environment that supplies little
energy.
2n en!yme cannot change an endergonic reaction into an e"ergonic one. 'n!ymes affect only
the rate of the reaction.
See f'(. 8.$" a%, 8.$-, pa(e $)" a%, $)-.
E"#ymes !"$ s/(str!tes
2 substrate is the molecule to which the en!yme binds during a chemical reaction
'n!ymes are substrate specific. 'ach type of en!yme cataly!es a particular reaction.
The substrate binds to the en!yme at a specific location called the !cti,e site of the en!yme.
The active site is usually formed by a few amino acids forming a sort of pocket on the surface of
the en!yme. 2ll other amino acids provide the framework for the en!ymatic protein.
The specificity of the en!yme depends on the fit between the shape of the substrate and the
shape of the active site.
The en!yme and the substrate form the e"#yme1s/(str!te com%le2.
The binding of the substrate to the active site causes the en!yme to change shape i"$/ce$ fit
and brings chemical groups of the substrate into the right position for the reaction to occur.
The induced fit causes also some distortion of the bonds of the substrate.
The pro"imity of orientation of the reactants together with strains in their chemical bonds
facilitates the breakage of old bonds and the formation of new ones.
2ctive sites may provide in some cases a microenvironment conducive to particular type of
chemical reaction e.g. lowering the p8 that will facilitate the transfer of 8
A
to the substrate as
part of the reaction process. See f'(. 8.$), pa(e $)).
The concentration of the substrate is important in determining the rate of the reaction.
*f the concentration of substrate is very high all the en!yme molecules will have their active
sites filled and the rate will depend only on the speed at which the en!yme can convert the
reactant to product. *n this case the en!yme is s!t/r!te$.
Im%ort!"ce of the cellCs %hysic!l !"$ chemic!l e",iro"me"t'
Temperature p8 and the presence of certain chemical affect the activity of en!ymes.
/. 'ffect of temperature
*ncreasing the temperature increases the number and strength of collisions between substrate
and en!yme molecules.
2fter a point an increase in temperature begins to disrupt the hydrogen bonds ionic bonds and
weak intermolecular attraction that give the en!yme molecule its particular shape thus affecting
the binding of substrate.
*f the temperature continues to increase the en!yme molecules lose their shape and become
$e"!t/re$.
The optimal temperature of an en!yme allows the greatest number of collisions without
denaturing the en!yme.
#or most en!ymes is between @D 0 F5JC. 8uman body temperature is about @L.8JC& it
ranges between @L.? and @?.1 degrees C (K80KK degrees #).
The en!ymes of hot0spring bacteria have an optimal temperature of about ?5JC.
1. 'ffect of p8.
The environmental p8 also affects en!ymatic activity.
8
A
can alter the charges on the en!yme. Changes in charges can alter the ionic bonds that
contribute to the tertiary and quaternary structures of the en!yme thus changing the protein<s
conformation and activity.
Many en!ymes become irreversibly denature in environments that are too acidic or too basic.
The optimal p8 for most en!ymes is between L 0 8.
Cof!ctors !"$ coe"#ymes
7ome en!ymes consist of two components a protein called the !%oe"#yme and another
chemical component called a cof!ctor.
2 cofactor may be an inorganic ion or an organic molecule. Many trace elements act as
cofactors e.g. Tn Cu.
2n organic non0polypeptide cofactor that binds to an en!yme is called a coe"#yme.
Cofactors may be permanently bound to the en!yme or loosely bound and reversible in their
binding.
Most vitamins are coen!ymes or the raw material from which coen!ymes are made.
E"#ym!tic i"hi(itio"
Most en!ymes can be inhibited or destroyed by some chemical agents.
Re,ersi(le i"hi(itio" occurs when the inhibitor forms a weak chemical bond with the en!yme.
There are two forms of reversible inhibition.
Com%etiti,e i"hi(itio" happens when the substrate and the inhibitor compete for the
active site of the en!yme. These competitive inhibitors mimic the substrate. *f the
concentration of substrate increases the rate increases.
No"com%etiti,e i"hi(itio" occurs when the inhibitor binds to an !llosteric site and
modifies the shape of the en!yme molecule rendering it inactive.
Irre,ersi(le com%etitio" occurs when an inhibitor combines with an en!yme and permanently
inactivates it. The inhibitor form strong covalent bonds with the en!yme.
Many poisons are permanent inhibitors e.g. mercury lead cyanide pesticides.
Many antibiotics and drugs are en!yme inhibitors that affect bacterial growth e.g. sulfa
drugs penicillin.
The selective inhibition and activation of en!ymes in the cell is an essential mechanism in the
control of metabolism.
See f'(. 8.$+, pa(e $)..
EDOLUTION OF ENBYMES
4atural selection acting on organisms with mutant genes encoding altered en!ymes is a ma%or
evolutionary force responsible for the diverse array of en!ymes found in organisms.
2 permanent change in a gene a mutation can result in a protein with one or more changed
amino acids. *f the changed amino acids are in the active site or some other crucial region the
altered en!yme might have a new activity or might bind to a different substrate.
T.E CONTROL OF METABOLISM
1. 2llosteric regulation.
7ome en!ymes have an allosteric site to which a substance can bind changing the en!yme<s
activity. This binding is usually weak.
The allosteric site is remote from the active site.
7ubstances that affect en!ymatic activity by binding to allosteric sites are called !llosteric
re/l!tors. 7ome are inhibitors others are activators.
Most allosteric en!ymes are constructed from two or more polypeptide chains called s/(/"its.
These en!ymes change back and forth between an active conformation and an inactive
conformation.
2n allosteric activator stabili!es the shape of the en!yme in its active form where the active site
is capable of receiving the substrate.
2ll subunits have an active and an allosteric site and the attachment of an allosteric regulator to
one of the subunits causes the shape change that is then transmitted to all other subunits of the
en!yme.
The rate of the reaction may be affected by the concentration of the regulators. *n some cases
the inhibitor and the activator are similar enough to compete for the same allosteric site.
,epending which of the two regulators is in greater quantity the ma%ority of the en!ymes will be
activated or inhibited.
2. Cooperativity
Cooperativity is a mechanism by which the binding of one substrate molecule changes the
conformation of the other subunits of the en!yme in order to accept more substrate molecules. *f
an en!yme has two or more subunits a substrate molecule causing induced fit in one subunit
can trigger the same favorable conformational change in all the other subunits of the en!yme.
The active form is stabili!ed by the substrate binding to one active site. -ne substrate molecule
makes the other sites receptive to other substrate molecules.
3. #eedback inhibition.
Fee$(!c* i"hi(itio" occurs when the final product inhibits one of the intermediate steps of the
pathway thus stopping further synthesis of the product.
Loc!li#!tio" of e"#ymes
Cells are not a membranous sac with en!ymes and substrates mi"ed in a random fashion.
'n!ymes are organi!ed to perform a sequence of chemical reactions in which the product of
one reaction becomes the substrate of the ne"t reaction.
This is called a met!(olic %!th&!y.
7ome en!ymes are grouped into multien!yme comple"es. 7ome of these comple"es are
located within the cell and organelle membranes and others are is solution within the
organelles.
'n!ymes help keep the orderly chemistry characteristic of life metabolism.
S/mm!ry3
@. Metabolism$ anabolism catabolism 0 definitions
F. 'nergy work potential and kinetic energy chemical energy N definitions
D. ;aws of Thermodynamics N know them and their implications for living organisms
L. #ree energy entropy and enthalpy N relation to spontaneous.non0spontaneous processes
?. 'ndergonic and '"ergonic reactions N catabolic and anabolic reactions
8. 7tructure of 2T= and 2,=
K. Coupled reactions N how do they work& energy e"change
/5. 'n!ymes
2ctivation energy
'n!ymes and substrates
'ffect of temperature and p8
Cofactors and coen!ymes
'n!ymatic inhibition
o Competitive inhibition and non0competitive inhibition
o Ieversible and irreversible inhibition
//. Control of metabolism
2llosteric control
Cooperativity
#eedback inhibition
/1. ;ocation of en!ymes