FOUNDATIONS*OF*

BIOCHEMISTRY*
Chapter*1*
Part*2*of*2*
PHYSICAL*FOUNDATIONS*
 PHYSICAL*FOUNDATIONS*
The$molecules$and$ions$contained$within$a$living$organism$
differ$in$KIND$and$in$CONCENTRATION$from$those$in$the$
organism’s$surroundings.$

ORGANISM:*
COMPOSITION*A*
SURROUNDINGS:*
COMPOSITION*B*

COMPOSITION*A* COMPOSITION*B*
 PHYSICAL*FOUNDATIONS*
Once$organisms$have$reached$maturity,$they$all$tend$to$
MAINTAIN*$a$constant$chemical$composi<on$in$the$face$of$
constantly$changing$surroundings.$$

ORGANISM*
constant*
(steady)*
SURROUNDINGS* composiJon*
 PHYSICAL*FOUNDATIONS*
Although$the$specific$composi<on$of$a$certain$organism$changes$li@le$
through$<me,$the$popula<on$of$molecules$within$the$organism$
changes$all$the$<me.$
Chemical$reac<ons$are$constantly*happening*to$replace$molecules$
and$cells$that$are$degraded.$$

The$constancy$of$types$and$concentra<on$of$molecules$and$cells$in$a$
organism$is$not$the$results$of$a$sta<c$state$but$instead$the$result$of$a$

DYNAMIC*STEADY*STATE*
 PHYSICAL*FOUNDATIONS*
In$this$dynamic$steady$state,$MATTER*and*ENERGY*is*EXCHANGED*
between$the$organism$and$the$surrounding,$and$the$separa<on$
(unequal*composiJon)$between$the$two$is$maintained.$$

maPer*and*energy*
SURROUNDINGS* ORGANISM*

MAINTAINING$this$dynamic$steady$state$REQUIRES$the$constant$
investment$of$

ENERGY*
 PHYSICAL*FOUNDATIONS*
When$the$cell$can$no$longer$make$use$of$the$necessary$energy,$
energy,$it$DIES$and$begins$to$decay$toward$

EQUILIBRIUM*

with$its$surroundings.$
 PHYSICAL*FOUNDATIONS*
A$dis<nc<on$must$be$made$between$the$system$and$the$
surroundings.$
SYSTEM*
• $$The$system$is$that$por<on$of$the$universe$with$which$we$are$
concerned.$It$might$be$a$mixture$of$chemicals$in$a$test$tube,$or$a$
single$cell,$or$an$en<re$organism.$

SURROUNDINGS*
• $$The$surroundings$include$everything$else$in$the$universe.$

system*

surroundings*
 PHYSICAL*FOUNDATIONS*

No*exchange*of*maPer*or*
isolated*
energy.*
system*

Energy*exchange*may*occur* closed*
system*

Energy*exchange*and/or* open*
maPer*exchange*may*occur* system*
 THERMODYNAMICS*REVIEW*
FIRST*LAW*
The$first$law,$also$known$as$Law$of$Conserva<on$of$Energy,$states$that$
energy$cannot$be$created$or$destroyed$in$a$chemical$reac<on.$The$
total$quan<ty$of$energy$in$the$universe$stays$the$same.$

SECOND*LAW*
The$second$law$of$thermodynamics$states$that$the$entropy$(disorder)$
of$any$isolated$system$always$increases.$

THIRD*LAW*
The$third$law$of$thermodynamics$states$that$the$entropy$of$a$system$
approaches$a$constant$value$as$the$temperature$approaches$absolute$
zero.$
 FIRST*LAW**
OF**
THERMODYNAMICS*
(HEAT)*
(ENTHALPY,*H)*
 ENERGY*IN*CHEMICAL*REACTIONS*
FIRST*LAW*
The$first$law,$also$known$as$Law*of*
ConservaJon*of*Energy,$states$that$
the$total$amount$of$energy$in$the$
universe$is$CONSTANT.$

In$other$words,$energy*cannot*be*created*or*destroyed*in*a*
chemical*reacJon.**

The$total$quan<ty$of$energy$in$the$universe$stays$the$same$
(it$is$constant).$$
This$means$that$all$of$the$energy$has$to$end$up$somewhere,$
either$in$the$original$form$or$in$a$different$from.$$
 ENERGY*IN*CHEMICAL*REACTIONS*
FIRST*LAW*

ΔEuniv$=$$ΔEsys$$+$$ΔEsurr$$=$$0$

system*

surroundings*
 ENERGY*IN*CHEMICAL*REACTIONS*
FIRST*LAW*
In$a$system$that$involves$chemical$reac2on$of$solids$and$
liquids,$$where$the$pressure$and$the$volume$don’t$change$
significantly,$the*energy*of*the*system*is*called**

ENTHALPY*

H*

ΔH*
 ENERGY*IN*CHEMICAL*REACTIONS*
FIRST*LAW*
In$very$simplified$terms,$the*enthalpy*can*be*describe*has*
the*HEAT*content*of*a*system.$$$$

Enthalpy*(H)**=**HEAT*CONTENT*

The$energy$of$a$system,$the$enthalpy$of$a$system,$the$heat$
content$of$a$system,$depends$on$the$chemical$nature$of$the$
system.$$

We*can*say*that*Enthalpy*(H)*depends*on*the*
number*and*kinds*of*chemical*bonds*in*a*system.*
 ENERGY*IN*CHEMICAL*REACTIONS*
FIRST*LAW*
During$a$chemical$reac<on,$bonds$are$broken$and$formed.$
During$a$chemical$reac<on,$enthalpy$changes$(ΔH).$

system* system*
Heat*content* Heat*content*
surroundings* surroundings*
BEFORE$ AFTER$
Chemical$reac<on$ Chemical$reac<on$

H* H*
 ENERGY*IN*CHEMICAL*REACTIONS*

In$a$chemical$reac<on,$when*bonds*are*broken,$$

energy*is*absorbed*

ENERGY$
REQUIRING$
PROCESS$

The$energy$to$be$used$to$break$bonds$in$the$system$must$
come$from$somewhere.$
That$energy$must$come$from$the$surroundings.$
 ENERGY*IN*CHEMICAL*REACTIONS*

In$a$chemical$reac<on,$when*bonds*are*formed,$$

energy*is*released*

ENERGY$
RELEASING$
PROCESS$

The$energy$released$from$the$systems$must$go$somewhere.$
That$energy$goes$to$the$surroundings.$
 ENERGY*IN*CHEMICAL*REACTIONS*

When$bonds*are*broken,$ When$bonds*are*formed,$
energy$must$be$absorbed$ energy$must$be$released$
from$the$surroundings$into$ from$the$system$into$the$
the$system.$ surroundings.$

heat* heat*
system* system*

surroundings* surroundings*

When*chemical*reacJons*occur,*there*is*always*an*
exchange*of*energy.***
 ENERGY*IN*CHEMICAL*REACTIONS*
CH4$$+$2$O2* CO2$$+$$2$H2O$*

heat* heat*
system* system*

surroundings* surroundings*
bonds*are*broken$ bonds*are*formed$
We$know$that$when$this$par<cular$reac<on$occurs,$heat$is$
released.$$
But$we$know$that$heat$was$absorbed$first!$
The$amount$of$energy$absorbed$to$break$bonds$and$amount$
of$the$energy$released$to$formed$new$bonds$are$not$the$
same!$
 ENERGY*IN*CHEMICAL*REACTIONS*
CH4$$+$2$O2* CO2$$+$$2$H2O$*

heat* heat*
system* system*

surroundings* surroundings*
bonds*are*broken$ bonds*are*formed$
When$this$par<cular$reac<on$occurs,$more*heat*is*released*
than*absorbed.**
These$types$of$reac<ons$are$called$

EXOTHERMIC*
 ENERGY*IN*CHEMICAL*REACTIONS*
CH4$$+$2$O2* CO2$$+$$2$H2O$*

heat* heat*
system* system*

surroundings* surroundings*
bonds*are*broken$ bonds*are*formed$
When$this$par<cular$reac<on$occurs,$more*heat*is*absorbed*
than*released.$$
These$types$of$reac<ons$are$called$

ENDOTHERMIC*
 ENERGY*IN*CHEMICAL*REACTIONS*

Some$reac<ons$give$off$ Other$reac<ons$absorb$
energy$as$heat;$these$are$ energy$as$heat,$making$the$
called$EXOTHERMIC* surroundings$cooler;$these$
(‘exo’$meaning$outside,$ are$called$ENDOTHERMIC$
‘thermic’$meaning$heat)$$$ (‘endo’$meaning$inside)$$

NET* NET*
heat* heat*
system* system*

surroundings* surroundings*
 ENERGY*IN*CHEMICAL*REACTIONS*

In$an$exothermic$reac<on,$
energy*is*released*into$the$
surroundings$as$heat.$
As$a$result,$the$
temperature*of*the*
surroundings*increases.*
In$an$endothermic*reac<on,$
energy*is*absorbed*from$the$
surroundings$as$heat.$
As$a$result,$the$
temperature*of*the*
surroundings*drops.*
 ENERGY*IN*CHEMICAL*REACTIONS*
Have$you$ever$bumped$your$head$or$twisted$your$ankle,$
and$had$a$nurse$put$a$cold$pack$on$your$$
injury?$$$
You$may$have$no<ced$he$or$she$did$not$take$
the$pack$out$of$the$freezer—the$pack$had$
no$ice$in$it...yet$it$was$s<ll$cold!$$$
Or,$have$you$ever$been$outside$on$a$cold$day$
and$used$gel$hot$packs$to$keep$your$hands$
warm?$You$may$remember$breaking$a$small$
disk$inside$the$gel,$and$feeling$it$get$hot$to$the$
touch.$$$
Both$the$cold$packs$and$the$hot$packs$use$chemistry$to$
change$their$temperature!$$
 SECOND*
OF**
THERMODYNAMICS*
(DISORDER)*
(ENTROPY,*S)*
 ENERGY*IN*CHEMICAL*REACTIONS*
SECOND*LAW*
The*second*law*of*thermodynamics*states*that*the*
DISORDER*in*the*universe*always*INCREASES.**
Ader$cleaning$your$room,$it$always$has$a$tendency$to$
become$messy$again.$$

This$is$a$result$of$the$second$law$of$thermodynamics.$
 ENERGY*IN*CHEMICAL*REACTIONS*
SECOND*LAW*
A$way$to$describe*the*system's*disorder*is$by$using$the$
term$$

ENTROPY*

S*

ΔS*
 ENERGY*IN*CHEMICAL*REACTIONS*
SECOND*LAW*EXAMPLES*

LOWER*ENTROPY* HIGHER*ENTROPY*
 ENERGY*IN*CHEMICAL*REACTIONS*
SECOND*LAW*EXAMPLES*

An$$ A$more$$
IMPROBABLE$$ PROBABLE$$
way$for$bricks$to$fall$ way$for$bricks$to$fall$
 ENERGY*IN*CHEMICAL*REACTIONS*
SECOND*LAW*EXAMPLES*

This*change*is**
SPONTANOUS*

ΔS*
is*
more*ordered* less*ordered*
posiJve*
low*probability* high*probability*
 ENERGY*IN*CHEMICAL*REACTIONS*
SECOND*LAW*EXAMPLES*
 ENERGY*IN*CHEMICAL*REACTIONS*
SECOND*LAW*EXAMPLES*
 THERMODYNAMICS*REVIEW*
CreaJng*and*maintaining*order*requires*work*(energy).*
When$polymeric$molecules$such$as$proteins$are$formed,$the$
monomers$(amino$acids)$need$to$be$assembled$in$a$very$specific$
order.$

4*

2*
This$would$represent$$ 3*
4* increased*order*
1*
ENTROPY*CHANGE**
(ΔS)* 2*
3*

1*
 THERMODYNAMICS*REVIEW*
Any$change*in*randomness*of$the$system$is$expressed$as$
entropy*change.$
By$conven<on,$ΔS$has$a$posiJve$value$when$randomness*increases.*

ΔS#<#0##*

ΔS#>#0##*
GIBB’S*FREE*ENERGY*
(G)*
(ΔG)*
 PHYSICAL*FOUNDATIONS*
J.$Willard$Gibbs,$who$developed$the$theory$of$energy$
changes$during$chemical$reac<ons,$showed$that$the$
free*energy*content,*G,$of$any$closed$system$can$be$
defined$in$terms$of$three$quan<<es:$

1)$enthalpy,*H#
reflec<ng$the$number$and$kinds$of$bonds$ 1839$–$1903$

2)$entropy,*S#
reflec<ng$the$degree$of$disorder$

3)$the*absolute*temperature,*T*(in$degrees$Kelvin)$
 PHYSICAL*FOUNDATIONS*
The$defini<on$of$free$energy$is:$

G#=#H#–#TS#

The$CHANGE$in$Gibbs$free$energy$for$a$PROCESS$is$wri@en$as$ΔG$
which$is:$
ΔG*=*GFINAL**b**G*INITIAL*

For$a$chemical$reac<on,$we$can$rewrite$the$equa<on$for$Gibbs$free$
energy$in$terms$of$changes$(Δ)$in$the$enthalpy$(ΔH)$and$entropy$(ΔS):$

ΔG#=#ΔH#–#TΔS#
 PHYSICAL*FOUNDATIONS*
When$a$chemical*reacJon*occurs$at$constant$temperature,$
the$freebenergy*change,*ΔG,$is$determined$by$

ΔG#=#ΔH#–#TΔS#

the$enthalpy$change,$$ the$entropy$change,$
reflec<ng$the$kinds$and$ describing$the$change$in$
numbers$of$chemical$ the$system’s$randomness$
bonds$and$noncovalent$
interac<ons$broken$and$
formed$$
 PHYSICAL*FOUNDATIONS*

A$process$tends$to$occur$spontaneously$only$if$ΔG*
is*negaJve.$
ΔG#=#ΔH#–#TΔS#

How$is$spontaneity$of$a$reac<on$defined?$

A$reac<on$is$said$to$be$spontaneous$if$it$occurs$without$being$driven$
by$some$outside$force.$

A*spontaneous*reacJon*is*a*reacJon*that**
FAVORS*THE*FORMATION*OF*THE*PRODUCTS*
at*the*condiJons*under*which*the*reacJon*is*occurring*
 PHYSICAL*FOUNDATIONS*
A$bonfire$is$an$example$of$a$spontaneous$
reac<on.$$
A$fire$is$exothermic,$which$means$a$decrease$
in$the$energy$of$the$system$as$energy$is$
released$to$the$surroundings$as$heat.$$

ΔG#=#ΔH#–#TΔS#

The$products$of$a$fire$are$composed$mostly$of$gases$(CO2$and$H2O),$so$
the$entropy$of$the$system$increases$during$most$combus<on$
reac<ons.$$

This$combina<on$of$a$decrease$in$energy$and$an$increase$in$entropy$
means$that$combus<on$reac<ons$occur$spontaneously*(negaJve*ΔG).$
 PHYSICAL*FOUNDATIONS*
A*nonspontaneous*reacJon*is*a*reacJon*that*does*not*favor*the*
formaJon*of*products*at*the*given*set*of*condiJons.*

In$order$for$a$reac<on$to$be$nonspontaneous,$one$or$both$of$the$
driving$forces$must$favor$the$reactants$over$the$products.$$

ΔG#=#ΔH#–#TΔS#

In$other$words,$the$reac<on$is$endothermic,$is$accompanied$by$a$
decrease$in$entropy,$or$both.$The$result$will$be$a$posiJve*ΔG.#*
 PHYSICAL*FOUNDATIONS*
Our$atmosphere$is$composed$primarily$of$a$mixture$of$nitrogen$and$
oxygen$gases.$$

One$could$write$an$equa<on$showing$these$gases$undergoing$a$
chemical$reac<on$to$form$nitrogen$monoxide.$

O2(g)$$$$+$$$$N2(g)$ 2$NO(g)$$

Fortunately,$this$reac<on$is$nonspontaneous$at$normal$temperatures$
and$pressures.$It$is$a$highly$endothermic$reac<on$with$a$slightly$
posi<ve$entropy$change$.$$

However,$nitrogen$monoxide$is$capable$of$being$produced$at$very$high$
temperatures,$and$this$reac<on$has$been$observed$to$occur$as$a$result$
of$lightning$strikes.$
 PHYSICAL*FOUNDATIONS*

ΔG*<*0* Favorable,*spontaneous*reacJon*

ΔG*>*0* Unfavorable,*non*spontaneous*reacJon*

The*value*of*ΔG**
allows*us*to*PREDICT*the**
DIRECTION*of*a*reacJon*
 PHYSICAL*FOUNDATIONS*
The$free$energy$of$FORMATION$of$LARGE$MOLECULES$is$POSITIVE.$$

ΔG*>*0*
Unfavorable,**
non*spontaneous*reacJon*

To*carry*out*these*thermodynamically*unfavorable*reacJons*energy*is*
required*and*the*process*is*called**

ENDERGONIC*
 PHYSICAL*FOUNDATIONS*
A$chemical$process$that$releases*energy*is$called$$

EXERGONIC*

ΔG*<*0*
favorable,**
spontaneous*reacJon*
 PHYSICAL*FOUNDATIONS*

endergonic** coupling* exergonic**

reacJons** reacJons**

To$carry$out$these$thermodynamically$unfavorable,$energyorequiring$
(endergonic)$reac<ons,$cells$COUPLE$them$to$other$reac<ons$that$
liberate$free$energy$(exergonic$reac<ons),$so$that$the$

OVERALL*process*is*EXERGONIC*

the*sum*of*the*free*energy*changes*is*negaJve**
 PHYSICAL*FOUNDATIONS*
The$most$common$SOURCE*OF*FREE*ENERGY*in$coupled$biological$
reac<ons$is$the$energy$released$by$hydrolysis$of$phosphoanhydride$
bonds.$

phosphoanhydride$

HYDROLYSIS*
 PHYSICAL*FOUNDATIONS*
The$best$known$example$(there$are$other$important$examples,$see$
chapter$13)$of$hydrolysis$of$phosphoanhydride$bonds$is$the$hydrolysis$
of$adenosine$triphosphate$(ATP).$
veryyyyy important!!!!!!

phosphoanhydride*
bond*

phosphoanhydride*
bond*
PHYSICAL*FOUNDATIONS*
 PHYSICAL*FOUNDATIONS*

monomers$ polymer$ ENDERGONIC$

ΔG1$posi<ve$

P$$ P$$ P$$ P$$ P$$ +$$ P$$ EXERGONIC$

ΔG2$nega<ve$

net*ΔG*negaJve*

When$these$reac<ons$are$coupled,$the$sum$of$ΔG1$and$ΔG2$is$
nega<ve:$the*OVERALL*process*is*EXERGONIC.$

By$this$coupling$strategy,$cells$are$able$to$synthesize$and$maintain$the$
informa<onorich$polymers$essen<al$to$life.$
 PHYSICAL*FOUNDATIONS*
In$thinking$about$energy$coupling,$it$is$useful$to$consider$a$simple$
mechanical$example:$
Object$has$$
Pulling$device$ poten<al$energy$ Object$tends$to$
(coupling)$ (spontaneously)$
slide$

The*greater*the*elevaJon*of*the*larger*object,*the*greater*the*energy*
released*(G)*as*the*object*slides*downward*and*the*greater*the*
amount*of*work*that*can*be*accomplished.*
 PHYSICAL*FOUNDATIONS*
The$breakdown$of$ATP$is$the$exergonic$reac<on$that$drives$many$
endergonic$processes$in$cells.$$

ATP$is$the$major$carrier$of$chemical$energy$in$all$cells.$
 PHYSICAL*FOUNDATIONS*

Freebenergy*change,*ΔG#
is$the$$
the*amount*of*energy*available*to*do*work**

G$is$called$the$FREE$energy$because$$
ΔG*represents*the*amount*of*energy*released**
as*a*process*moves*TOWARD*equilibrium**
that$is$available$to$perform$work$or$drive$another$reac<on.$

Not$all$the$energy$released$during$a$chemical$reac<on$is$available$to$
do$useful$work.$Some$is$always$lost$as$heat.$$
 PHYSICAL*FOUNDATIONS*
***chem 102 material regarding Le Chatelier’s Principle
Let's$describe$the$ΔG$that$takes$place$in$a$chemical$reac<on.$

forward$reac<on$$
aA$$$$+$$$bB$ cC$$$$+$$$dD$
reverse$reac<on$$

What$will$happen$if$we$mix$A,$B,$C,$and$D$together$at$arbitrary$
concentra<ons?$
Well,$it$depends.$$

Each$compound$(A,$B,$C,$D)$involved$in$the$chemical$reac<on$contains$
a$certain$amount$of$energy,$poten<al$energy,$related$to$the$kind$and$
number$of$its$bonds$(H).$Also,$it$is$associated$with$a$certain$entropy$
(S).$$$

Each$compound$has$certain$free$energy$G.$$
 PHYSICAL*FOUNDATIONS*

forward$reac<on$$
aA$$$$+$$$bB$ cC$$$$+$$$dD$
reverse$reac<on$$

Chemical$reac<ons$proceed$spontaneously$un<l$EQUILIBRIUM$is$
reached.$
When$a$system$is$at$equilibrium,$the$RATE$of$product$forma<on$
exactly$EQUALS$the$rate$at$which$product$is$converted$to$reactant.$

At*equilibrium**

RATE$ RATE$
FORWARD$ BACKWARD$
 PHYSICAL*FOUNDATIONS*

When$the$rate$of$product$forma<on$exactly$equals$the$rate$at$which$
product$is$converted$to$reactant$there$is$not$change$in$concentra<ons$
of$reactants$and$products$(equilibrium$is$reached).$
Since$at$equilibrium$the$concentra<ons$of$reactants$and$products$do$
not$change,$their$ra<o$is$a$constant$and$is$called$
equilibrium*constant*of*the*reacJon:**

[Ceq]c*[Deq]d****
*Keq** =*
[Aeq]a*[Beq]b**
Keq is a ratio of the concentration (doesnt change at eqb)
 PHYSICAL*FOUNDATIONS*

[Ceq]c*[Deq]d****
*Keq** =*
[Aeq]a*[Beq]b**

Keq*>*1* There$is$a$higher$propor<on$of$products$to$reactants.$
The$forma<on$of$products$is$favored.$$
The$posi<on$of$the$equilibrium$lies$more$to$the$right.$

Keq*<*1* There$is$a$higher$propor<on$of$reactants$as$not$many$of$these$
are$converted$into$products.$
Reverse$reac<on$is$favored.$
The$posi<on$of$the$equilibrium$lies$more$to$the$led.$

Keq*=*1* The$concentra<ons$of$both$reactants$and$products$are$
almost$the$same.$There$is$no$preference.$ 58$
 PHYSICAL*FOUNDATIONS*

[Ceq]c*[Deq]d****
*Keq** =*
[Aeq]a*[Beq]b**

The$MAGNITUDE$and$the$SIGN$of$the$EQUILIBRIUM$CONSTANT$
expresses$tendency*of*a*chemical*reacJon*to*go*to*compleJon.*$

The*value*of*the*equilibrium*constant**
depends*exclusively*on*the*idenJty**
of*the*chemical*species*involved*in*the*reacJon.**

We’ll$see$shortly$that$ΔG$depends$on$the$equilibrium$constant.$$
 PHYSICAL*FOUNDATIONS*

The$change$in$energy$as$the$system$moves$from$its$iniJal*state*to*
equilibrium,$with$no$changes$in$temperature$or$pressure,$is$
the$freeoenergy$change,$ΔG.$

ΔG$
iniJal*state$ equilibrium$
Energy#
change$

The*magnitude*of*ΔG$depends*on*

1)*the*parJcular*chemical*reacJon*
2)*how*far*from*equilibrium*the*system*is*iniJally*
 PHYSICAL*FOUNDATIONS*

In$other$words,$the$ΔG$of$a$chemical$reac<on$depends$on$the:$

1)*free*energy*content*of*reactants*and*products*(idenJty*of*
reactants*and*products)*

2)*iniJal*concentraJons*of*reactants*and*products**

These$two$factors$are$expressed$in$the$following$equa<on:$

[Ci]c*[Di]d****
ΔG#=#ΔG°#+#RT*ln*#*
[Ai]a*[Bi]b**
 PHYSICAL*FOUNDATIONS*
If$the$ini<al$concentra<ons$of$reactants$are$higher$than$the$ini<al$
concentra<ons$of$products,$the$raJo*is*LESS*than*1,*and$the$
logarithmic$term$is$nega<ve.$

[Ci]c$[Di]d$$$$
ΔG$=$ΔG°$+$RT$ln$$*
[Ai]a$[Bi]b$$

nega<ve*
That$means$that$the$reac<on$will$have$a$more$NEGATIVE*(favorable)*
free*energy*change.$$
In$other$words,$there$is$a$greater$tendency$for$the$reac<on$to$proceed$
forward$un<l$equilibrium$is$reached.$
 PHYSICAL*FOUNDATIONS*
If$the$ini<al$concentra<ons$of$products$are$higher$than$the$ini<al$
concentra<on$of$reactants,$the$raJo*is*GREATER*than*1,*and$the$
logarithmic$term$is$posi<ve.$

[Ci]c$[Di]d$$$$
ΔG$=$ΔG°$+$RT$ln$$*
[Ai]a$[Bi]b$$

posi<ve*
That$means$that$the$reac<on$will$have$a$more$POSITIVE*(unfavorable)*
free*energy*change.$$
The$reac<on$wants$to$go$in$the$direc<on$that$decreases$the$products$
and$increases$the$reactants.$
 PHYSICAL*FOUNDATIONS*

By*definiJon,*at*EQUILIBRIUM,*the*driving*force*in*either*direcJon*is*
the*same,*so*that*the*net*driving*force*is*zero.**

In$other$words,$the*free*energy*change*is*zero.$

at*equilibrium*
ΔG#=#0*#*
 PHYSICAL*FOUNDATIONS*

[Ci]c$[Di]d$$$$
ΔG$=$ΔG°$+$RT$ln$$*
[Ai]a$[Bi]b$$

At$equilibrium:$$
[Ci]c$[Di]d$$$$ [Ceq]c$[Deq]d$$$$
ΔG$=$0$ and$ =$ =$Keq$
[Ai]a$[Bi]b$$ [Aeq]a$[Beq]b$$

0$=$ΔG°$+$RT$ln$Keq$$*

#ΔG°#=#9#RT*ln*Keq*#*
 PHYSICAL*FOUNDATIONS*

$ΔG°$=$E$RT$ln$Keq$$$

The$above$equa<on$tells$us$that$the$ΔG$of$a$reac<on$depends$not$only$
on$the$ini<al$concentra<ons$of$reactants$and$products$but$also$on$the$
equilibrium$constant$of$the$reac<on$

[Ci]c$[Di]d$$$$
ΔG$=$ΔG°$+$RT$ln$$*
[Ai]a$[Bi]b$$

Term$specific$for$a$ Term$that$expresses$ini<al$
par<cular$reac<on$ concentra<ons$of$reactants$
and$products$
 PHYSICAL*FOUNDATIONS*

Let's$evaluate$the$free$energy$change$ΔG$for$a$reac<on$when$the$
INITIAL*concentraJons*of*all*reactants*and*products*are*at*1*M.$

Under$these$condi<ons,$the$concentraJon*term*is*zero*and$the$free$
energy$change$is$equal$to$the$standard$free$energy$change.$

[Ci]c$[Di]d$$$$
ΔG$=$ΔG°$+$RT$ln$$* ΔG#=#ΔG°#*#*
[Ai]a$[Bi]b$$

ΔG°*is*the*standard*free*energy*change**
when*the*iniJal*concentraJon*of*all*the*
consJtuents*are*1*M*(standard*states).*
 PHYSICAL*FOUNDATIONS*
Don't$get$confused$on$this$point:$$ΔG°$is$NOT$the$free$energy$change$
at$equilibrium$(that's$zero!).$

ΔG°*is*the**
DRIVING*FORCE*OF*THE*REACTION*
*when*we*have*set*all*the*iniJal*concentraJons*at*1*M*

ΔG°$is$a$convenient$way$to$compare$different$reac<ons$under$
standard$condi<ons.$

The$standard$value$ΔG°$is$determined$from$experimental$data$and$
allows$the$evalua<on$of$ΔG$for$other$experimental$condi<ons$in$which$
the$concentra<ons$of$reactants$and$products$are$not$1M.$
PHYSICAL*FOUNDATIONS*
 PHYSICAL*FOUNDATIONS*

$ΔG°$=$E$RT$ln$Keq$$$

From$this$equa<on$we$see$that$ΔG°$is$simply$a$second$way$(besides$
Keq)$of$expressing$the$driving$force$on$a$reac<on.$

Because$Keq$is$experimentally$measurable,$we$have$a$way$of$
determining$ΔG°,$the$thermodynamic$constant$characteris<c$of$each$
reac<on.$
greater
$Keq$>>$1$ ΔG°$is$large$and$nega<ve$

less
$Keq$<<$1$ ΔG°$is$large$and$posi<ve$
 PHYSICAL*FOUNDATIONS*
PRACTICE*PROBLEM*(1)**
The$equilibrium$constant,$Keq,$for$the$following$reac<on$is$2$x$105$M.$

ATP$ ADP$+$HPO42o$

If$the$measured$cellular$concentra<ons$are:$$
[ATP]$=$5$mM$$
[ADP]$=$0.5$mM$$
[HPO42o]$=$5$mM$$

is$this$reac<on$at$equilibrium$in$living$cells?$
 PHYSICAL*FOUNDATIONS*
PRACTICE*PROBLEM*(1)*b*soluJon*
The$defini<on$of$equilibrium$constant$for$this$reac<on$is:$

[ADP]$[HPO42o]$$
$Keq$$ =$
[ATP]$$

From$the$measured$cellular$concentra<on$given$above,$we$calculate$
the$massoac<on$ra<o,$Q:$$

[ADP]$[HPO42o]$$ [0.5$mM]$[5mM]$$
Q$ =$ =$ =$0.5$mM$=$5$x$10o4$M$$
[ATP]$$ [5$mM]$$
 PHYSICAL*FOUNDATIONS*
PRACTICE*PROBLEM*(1)*–*soluJon*(con’t)*

[ADP]$[HPO42o]$$ [0.5$mM]$[5mM]$$
Q$ =$ =$ =$0.5$mM$=$5$x$10o4$M$$
[ATP]$$ [5$mM]$$

This$value$is$far$from$the$equilibrium$constant$for$the$reac<on$(Keq$=$2$$
x$105$M),$so$the$reac<on$is$very$far$from$the$equilibrium$in$cells.$

[ATP]$is$far$higher$and$[ADP]$is$far$lower$that$is$expected$at$
equilibrium.$$

(How$can$a$cell$hold$its$[ATP]/[ADP]$$ra2o$so$far$from$equilibrium?$It$
does$so$by$con2nuously$extrac2ng$energy$(from$nutrients,$such$as$
glucose)$and$using$it$to$make$ATP$from$ADP$and$Pi.)$$
 PHYSICAL*FOUNDATIONS*
PRACTICE*PROBLEM*(2)*

Given$that$the$standard$free$energy$(ΔG°)$for$the$reac<on:$$

Glucose$$+$$Pi$$$ glucoseo6ophosphate$$

is$13.8$kJ/mol,$and$the$standard$free$energy$for$the$reac<on:$$

ATP$ ADP$+$HPO42o$

is$–30.5$kJ/mol,$what$is$the$free$energy$change$for$the$reac<on:$

Glucose$$+$$ATP$$$ glucoseo6ophosphate$+$$ADP$$
 PHYSICAL*FOUNDATIONS*
PRACTICE*PROBLEM*(2)*

Remember:$free$energy$changes$of$coupled$reac<ons$are$addi<ve.$$

Some$enzymeocatalyzed$reac<ons$like$the$one$in$this$prac<ce$problem$
are$interpretable$as$two*coupled*halfbreacJons,$one$spontaneous$and$
the$other$nonospontaneous.$

At$the$enzyme$ac<ve$site,$the$coupled$reac<on$is$kine<cally$facilitated,$
while$the$individual$halforeac<ons$are$prevented.$

The$free$energy$changes$of$the$halforeac<ons$may$be$summed,$to$
yield$the$free$energy$of$the$coupled$reac<on.$
 PHYSICAL*FOUNDATIONS*
PRACTICE*PROBLEM*(2)*b*soluJon*
We$can$write$the$equa<on$for$this$reac<on$as$the$sum$of$the$two$half$
reac<ons:$$

Glucose$+$Pi$$$ glucoseo6ophosphate$$ ΔG°1$=$13.8$kJ/mol$$

ATP$ ADP$+$HPO42o$ ΔG°2$=$–30.5$kJ/mol$

Sum:$ Glucose$$+$$ATP$$$ glucoseo6ophosphate$+$$ADP$$

ΔG°sum$=$–16.7$kJ/mol$

The$ΔG°$for$two$reac<ons$that$sum$to$a$third$is$simply$the$sum$of$the$
two$individual$reac<ons.$$

A$nega<ve$value$for$ΔG°$(–16.7$kJ/mol)$indicates$that$the$(overall)$
reac<on$will$tend$to$occur$spontaneously.$$
 PHYSICAL*FOUNDATIONS*
The$COUPLING$and$EXERGONIC$and$ENDERGONIC$reac<ons$is$central$
to$the$energy$exchanges$in$living$systems.$$

As$we$shall$see$in$chapter$13,$reac<ons$that$break$down$ATP$release$
energy$that$drives$many$endergonic$processes$in$cells.$$

ATP$breakdown$in$cells$is$exergonic$because$all$living$cells$maintain$a$
concentra<on$of$ATP$far$above$its$equilibrium$concentra<on.$It$is$this$
DISEQUILIBRIUM$that$allows$ATP$to$serve$as$the$major$carrier$of$
chemical$energy$of$all$cells.$$$
 PHYSICAL*FOUNDATIONS*
The$free$energy$change$of$a$reac<on$is$a$THERMODYNAMIC$
CONSTANT.$

The$free$energy$change$tells$us$where$the$equilibrium$for$a$reac<on$
lies$(toward$the$products$or$toward$the$reactants)$but$tells$us$nothing*
about*how*fast*that$equilibrium$will$be$achieved.$
key word constant

The$rates$of$reac<ons$are$governed$by$the$parameters$of$KINETICS.$
 PHYSICAL*FOUNDATIONS*
All$biological$macromolecules$are$much$less$thermodynamically$
stable$than$their$monomeric$subunits,$yet$they$are$kine<cally$stable:$

Non$spontaneous$
MONOMERS$ POLYMERS$ (thermodynamics)$

Fast$
MONOMERS$ POLYMERS$ (kine<cs)$

ENZYMES*
biocatalysts*
 PHYSICAL*FOUNDATIONS*
The$path$from$reactant(s)$to$product(s)$involves$an$energy$barrier,$
called$the$

ACTIVATION*ENERGY*
(ACTIVATION*BARRIER)*

REACTANTS$ PRODUCTS$

This*barrier*must*be*surmounted*for*ANY*reacJon*to*proceed.*
 PHYSICAL*FOUNDATIONS*
Ac<va<on$energy$is$the$energy$required$for$the$breaking$of$exis<ng$
bonds.$$

transi<on$
state$
Poten<al$energy$

AcJvaJon*
reactants$ *energy*

products$

Reac<on$progress$
 PHYSICAL*FOUNDATIONS*
In$living$systems,$ENZYMES$are$the$molecules$responsible$for$the$
lowering*of*the*acJvaJon*energy.$

Ac<va<on$energy$

Ac<va<on$energy$
with$catalyst$
PHYSICAL*FOUNDATIONS*
 PHYSICAL*FOUNDATIONS*

Enzymes$lower$ac<va<on$barriers$SELECTIVELY$(very$specific).$$

This$selec<vity$is$crucial$for$the$effec<ve$REGULATION$of$cellular$
processes.$

The$mul<tude$of$enzymeocatalyzed$chemical$reac<ons$in$cells$are$
FUNCTONALLY$ORGANIZED$into$many$

SEQUENCES*OF*CONSECUTIVE*REACTIONS**

in$which$the$product$of$one$reac<on$becomes$the$reactant$in$the$
next.$
 PHYSICAL*FOUNDATIONS*
These$sequences*of*consecuJve*reacJons*are$called$
catabolic = release energy by breaking down
complex molecules into simpler compounds;
“downhill”
PATHWAYS*
catabolic
“downhill”
exergonic
A$ enzyme$1$ B$ enzyme$2$ C$
enzyme$3$
D$
enzyme$4$
E$
PRODUCT
STARTING
(protein)
MOLECULE
anabolic
(amino acid) complex
“uphill”
simple (macromolecule)
endergonic
(building block)
anabolic = consume energy to
build complex molecules from
simpler ones; “uphill”
 PHYSICAL*FOUNDATIONS*
Other pathways start with small precursor
anabolic = consume energy molecules and convert them to progressively
larger and more complex molecules, including
to build complex molecules ANABOLISM* proteins and nucleic acids. Such synthetic
from simpler ones; “uphill” pathways which invariably require the input of
energy, are collectively designated anabolism

anabolism is the build up of building blocks to macromolecules? ex. synthesis of protein from amino acids
  *Building*block*   *Macromolecule*
simple complex
  *Simple*sugar*   *Polysaccharide*
  *Amino*acid*   *Protein*(pepJde)*
  *NucleoJde*   *RNA*or*DNA*
  *FaPy*acid*   *Lipid*
catabolism (must be) the breaking down of macromolecules to building blocks
ex. breakdown of glucose in presence of oxygen

Some pathways degrade organic nutrients into catabolic = release energy by

simple end products in order to extract
CATABOLISM*
chemical energy and convert it into a form
breaking down complex molecules
into simpler compounds;
useful to the cell; these degradative, free-
energy-yielding reactions are designated “downhill”
catabolism.
 PHYSICAL*FOUNDATIONS*
Cells$synthesize$macromolecules$in$the$PRECISE$PROPORTIONS$
required$by$the$cell$under$any$given$circumstance.$

For$example,$during$rapid$cell$growth$the$precursors$of$proteins$and$
nucleic$acids$must$be$made$in$large$quan<<es,$whereas$
in$non$growing$cells$the$requirement$for$these$precursors$is$much$
reduced.$

A$ ENZYME$$
B$

Enzymes$in$each$metabolic$pathway$are$regulated$so$that$each$type$
of$precursor$molecule$is$produced$in$a$quan<ty$appropriate$to$the$
current$requirements$of$the$cell.$
 PHYSICAL*FOUNDATIONS*

FEEDBACK*INIBITION*

is$an$example$of$regulaJon*of*metabolism.$

The$increased$concentra<on$of$the$reac<on$product$inhibits$the$
cataly<c$ac<vity$of$the$first$enzyme$in$the$pathway,$slowing$the$
produc<on$of$that$substance$$
Example$of$a$nega<ve$regula<on:$product$of$enzyme$5$inhibits$
enzyme$1$