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MCLLCuLA8 CLLL 8lCLCC?

8LvlSlCn nC1LS
PkOk4kYO15 Lu8AC1L8lA (18uL 8AC1L8lA) A8CPAL8AC1L8lA (Lx18LMCPlLLS") (LC PALCPlLLS 8LC PlCP SAL1
1PL8MCACluCPlLLS?)
O ALL A8L SlnCLLCLLLLu C8CAnlSMS
O roLeln Cell wall
O naked clrcular unA
O CSSLSS A SlMLL ln1L8nAL S18uC1u8L Wl1PCu1 A WLLL uLllnLu nuCLLuS
uk4kYO15 CCM8lSL ALL nCn 8AC1L8lA
O Complex lnLernal sLrucLure lncludlng a well deflned nucleus
O Cenerally (buL noL always) larger Lhan prokaryoLes
O lnLracellular comparLmenLs (organelles) enable several complex reacLlons Lo occur aL same Llme
Ce|| Membrane
roLeln conLenL of membrane can vary beLween 1876
1hree Lypes of proLelns lnhablL lL |ntegra| (Lrans) per|phera| (ouLslde/lnslde) and ||p|d anchored (slgnalllng)
W Cytop|asm cyLosol (fluld) + organelles
W -c|eo|s densely sLalnlng fllamenLous reglon of unA assoclaLed wlLh r8nA synLhesls
W M|tochondr|a double membrane lnner membrane folded lnLo crlsLae proLrude lnLo maLrlx
W |bosomes made of 30S and 30S SubunlLs ln prokaryoLlc 60S and 40S ln eukaryoLlc
W o|g| packlng and LransporL proLelns proLeln synLhesls and packlng
9reparat|on for e|ectron m|croscopy llxaLlon freezlng embeddlng ln wax secLlonlng vla mlcroLome sLalnlng
vla heavy meLal

Sb ce|||ar fract|onat|on can be done by enzymes Lonlc buffers physlcal grlndlng sonlcaLlon chemlcals lonlc
deLergenLs eLc and Lhen d|fferent|a||y centr|fged by mass
n|stochem|stry SLalnlng enzymes by addlng a colorless subsLraLe LhaL ls caLalyzed Lo a colored one Slmllarly
Immnoh|stochem|stry ls where an anLlbody ls con[ugaLed Lo a florescenL marker or enzyme
Immnof|orescence ls where an anLlbody ls Lagged wlLh a flourochrome and vlewed wlLh a fluorescence
mlcroscope 1here lsa speclal form of Lhls called 'confoca|' mlcroscopy ln whlch Lhe lmage focuses upon a
speclflc focal plane raLher Lhan a blurry volume Clve sharp lmage buL no depLh
9rote|n d|gress|on he||x 36 res|de per trn n bonds rn para||e| vert|ca||y w|th he||x between am|de -n
and carbony| C Sheets n bond rn para||e| to cha|ns s|de grops can be para||e| or perpend|c|ar to each
other

lSCML8lSM
| and d |somers (+] |somers) An enanLlomer can be named by Lhe dlrecLlon ln whlch lL roLaLes Lhe plane of
polarlzed llghL lf lL roLaLes Lhe llghL clockwlse (dexLroroLaLory) (as seen by a vlewer Lowards whom Lhe llghL ls
Lravellng) LhaL enanLlomer ls labeled (+) lLs mlrrorlmage ls labeled (-) (levoroLaLory) 1he (+) and (-) lsomers
have also been Lermed and NO1 some os l ooJ u
and D |somers An opLlcal lsomer can be named by Lhe spaLlal conflguraLlon of lLs aLoms 1he u/L sysLem
does Lhls by relaLlng Lhe molecule Lo glyceraldehyde (hlghesL numbered lowesL on Lhe flsher pro[ecLlon chlral
carbon compared conflguraLlon Lo glyceraldehyde) lL does noL lndlcaLe whlch enanLlomer ls dexLroroLaLory
and whlch ls levoroLaLory 8aLher lL says LhaL Lhe compounds sLereochemlsLry ls relaLed Lo LhaL of Lhe
dexLroroLaLory or levoroLaLory enanLlomer of glyceraldehydeLhe dexLroroLaLory lsomer of glyceraldehyde
was ln facL Lhe u lsomer

S and |somers LowesL prlorlLy polnLed away S lf hlghesL Lo lowesL ptlotlty (on aLomlc mass) ls
counLerclockwlse 8 lf decrease ls clockwlse -o reference mo|ec|e 1he / 5 sysLem has no flxed relaLlon Lo
Lhe (+)/(-) sysLem An lsomer can be elLher dexLroroLaLory or levoroLaLory dependlng on lLs exacL
subsLlLuenLs 1he / 5 sysLem also has no flxed relaLlon Lo Lhe u/L sysLem
nantomers nonsuperposable mlrror lmages of each oLher
D|astereo|somers nonsuperposable nonmlrror lmages of each oLher eg a palr of enanLlomer
Chair conformation - A three-dimensional configuration consisting of a six-
membered ring in which all hydroxyl groups face away from the ring in an
equatorial position. The chair conformation is the most energetically stable of
all different forms of the ring. Bonding angles appear in the shape of a chair.
For an Organic Chemistry explanation of chair conformations, see Carbocycles.
ermlsslon ls granLed Lo copy dlsLrlbuLe and/or modlfy Lhls documenL under Lhe Lerms of Lhe -D Iree
Docmentat|on |cense verslon 12 or any laLer verslon publlshed by Lhe lree SofLware loundaLlon wlLh
no lnvarlanL SecLlons no lronLCover 1exLs and no 8ackCover 1exLs

Boat conformation - Slightly less stable than the chair conformation, the boat
conformation consists of a six-membered ring in which some of the hydroxyl
groups face toward the ring. Bonding angles appear in the shape of a boat. For an Organic
Chemistry explanation of chair conformations
Amlno aclds and naLurally L and mosL have S conflguraLlon

MosL naLural sugars are u
slJe oo vlew
|
CCCn
|n
CC-n2
D@9
Drac||
- 8ase
C@9
Cytos|ne
c |n D-

for blochemlcal molecules lefL handed 8lghL handed relaLlve Lo a screw clockwlse 8lghL
unA ls naLurally rlghL handed hellx (colncldenLly u nucleoLldes)
Alpha Pellcles are noL naLurally lefL handed accordlng Lo qulz
m|no c|ds
7 AA's as well as amlno and carboxyl groups can easlly accepL and donaLe proLons dependlng on Lhelr
envlronmenL
sssent|a| m|no ac|ds (cannot be b|osynthes|zed |n sff|c|ent amonts)
Pls lle Leu Lys MeL he 1hr 1rp val
-on essent|a| m|no ac|ds
Ala Arg Asn Asp Cys Clu Cln Cly ro Ser 1yr
1o remember Lhe nlne essenLlal amlno aclds for humans
lsoleuclneleuclnelyslneLhreonlnevallneLrypLophanhlsLldlne
meLhlonlnephenylalanlne remember Lhe senLence
"I |ove |yslne though Va| thlnks h|s meth's preferable"
8C1LlnS
9ept|de up Lo 2030 amlno acld resldues
9o|ypept|de longer
9rote|n a polypepLlde wlLh a well deflned 3u sLrucLure also generally Laken Lo be a naLural producL
woys oome ptotelos ftom tbe ftee omlooqtoop eoJ ooJ Jtow wltb omlooqtoop oo eft
epLlde bond amlde bond acld + amlne

As Lhe negaLlve charge ls spread lL resulLs ln Lhe keLone belng less
nucleophlllc comblned wlLh Lhe facL LhaL Lhe nlLrogen ls non
nucleophlllc (elecLron palr donaLor) due Lo poslLlve charge means LhaL lL
ls less reacLlve Lhan a sLandard keLone yeL posslble Lo break down 1he
group ls planar requlred for con[ugaLlon LwlsLlng Lhe bond breaks Lhe
con[ugaLlon buL a LwlsL of up Lo 20
o
appears accepLable 8 groups
prefers Lo slL ln Lrans conformaLlon oLher Lhan prollne whlch can do
boLh


Alpha hellces have hbonds verLlcally and ouLwards up Lhe hellx whllsL beLa sheeLs have h bonds parallel Lhe
chalns and can allgn parallel or perpendlcular Lo each oLher P bonds and vuW forces are compeLlng wlLh
waLer molecules hence weak for foldlng
Lnzymes lower Lhe free energy of acLlvaLlon (uC) for a reacLlon by a comblnaLlon of ralslng Lhe ground sLaLe
uC of Lhe subsLraLe and lowerlng Lhe uC of Lhe LranslLlon sLaLe (1S) for Lhe reacLlon

c|d]8ase ster hydro|ys|s and nzyme nc|eoph|||c cata|ys|s
LsLer + P
2
C
(l)
+ Acld Carboxyllc acld + Alcohol
LsLer + CP

(aq)
CarboxylaLe lon + Alcohol
Amlde bond + P
2
C
(l)
Carboxyllc acld + Amlne
5ee booJwtltteo sbeet oo tbls ooJ eozymes

CA88CP?u8A1LS
Pydrolysls lnLo monosaccharldes ls done by 6M PCl
Can be named by carbon number or by presence of groups 1rlose LeLrose penLose hexose or Aldose/keLose
Lnd's ln ose redc|ng oslde nonredc|ng
llsher pro[ecLlon
Chlral molecule 8oLaLe Carbon chaln unLll verLlcal and behlnd Lhe plane of Lhe paper uL Lhe Chlral aLom ln
Lhe plane of Lhe paper and puL Lhe hlghesL prlorlLy (cahn lngold prelog rules) aL Lhe Lop oLher groups on chlral
aLom pro[ecL ln fronL of Lhe plane of Lhe paper


1eLroses have 2 palrs of enanLlomers (dlasLerolsomers) le eryLhrose and Lhrlose Mlld oxldaLlon (dlluLe nlLrlc
acld) of elLher enanLlomer of eryLhose leads Lo Lhe same optlcoy looctlve form of 'LarLarlc acld'
Mlld oxldaLlon of Lhe Lwo enanLlomers of Lhrlose leads Lo 2 dlfferenL optlcoy octlve enanLlomers of LarLarlc
acld
A level organlc chemlsLry aldehyde + PCn new carbon Cn chaln
efox/n-
efox/n-
5etloe ltoteose


1he presence of a carbony| group and hydroxy groups ln Lhe same mo|ec|e allows sugars Lo form
|ntramo|ec|ar hemlaceLals Lhese can form onLo any CP group buL mosL commonly form onLo Lhe end one as
Lhls ls mosL sLable formlng perfecL rlngs

and glucose are ep|mers eplmers are dlasLereomers LhaL dlffer ln conflguraLlon of only one sLereogenlc
cenLer More speclflcally Lhey are anomers ln LhaL lL ls dlasLereomer of a saccharlde (ln Lhe cycllc form) LhaL
dlffers only ln lLs conflguraLlon aL Lhe hemlaceLal (or hemlkeLal) carbon also called Lhe anomer|c carbon
1hese forms of glucose are ln equlllbrlum because Lhe hemlaceLal rlng breaks and reforms wlLh a chance of
CP group belng ln a dlfferenL plane As Lhey boLh roLaLe llghL aL dlfferenL frequencles lL leads Lo a pure
soluLlon of alpha glucose changlng ln lLs llghL roLaLlon over Llme as lL degrades lnLo parL beLa glucose (and vlce
versa)

8lng names of monosaccharldes 4 carbon franose 3 carbon pyranose
C|||gosachhar|des few sugars Cne unlL musL be llnked by poslLlon 1 (hence usually Lhe anomerlc poslLlon)
and each unlL may be elLher furanose or pyranose
my|ose 14 g|cose + g|cose 9Cmer (same as ma|tose)
Ma|tose (14) glucose + glucose AceLal flxed ln alpha hemlaceLal ls free Lo change beLween and
Lherefore lL reduces lehllng's soluLlon le reduclng sugar
actose (14) galacLose + glucose AceLal flxed ln beLa hemlaceLal ls free Lo change reduclng sugar
Scrose (12) glucose + frucLose 8onded ln boLh Lhe anomerlc poslLlons of each Clucose anomerlc poslLlon ls
flxed ln lrucLose anomerlc poslLlon ls a keLal flxed ln a nonreduclng sugar
Cyc|odextr|ns 67 or 8 monosaccharldes [olned by 14 lormed by Lhe breakdown of starch by cerLaln
bacLerla Pave a buckeL llke sLrucLure hydrophlllc on ouLslde and hydrophoblc on Lhe lnslde as Lhe CP's face
ouL used by pharmaclsLs Lo make drugs more soluble by placlng ln Lhe buckeL Also can be used Lo
dlfferenLlaLe enanLlomer
9o|ysachhar|des
Starch 20amylose 80amylopecLln
my|ose llnlSP 1PlS Cll
AmylopecLln llnlSP 1PlS Cll
|ycos|des Sugar group blnded Lhrough anomerlc carbon Lo anoLher group vla glycosldlc bond (C or s or
n or 8!) A glyocosldlc bond ls a carbohydraLe bond from hemlaceLal Lo hydroxyl group

eg A1 unA uu nAu+
8LCL1C8 1PLC8?
9harmacok|net|cs how body affecLs Lhe drug
9harmacodynam|cs SlLe of acLlon of Lhe drug affecL of drug on Lhe body
||oster|c reg|at|on ls Lhe regulaLlon of an enzyme or oLher proLeln by blndlng an effecLor molecule aL Lhe
proLelns allosLerlc slLe (LhaL ls a slLe oLher Lhan Lhe proLelns acLlve slLe non compet|t|ve |nh|b|tor?) LffecLors
LhaL enhance Lhe proLelns acLlvlLy are referred Lo as oostetlc octlvotots whereas Lhose LhaL decrease Lhe
proLelns acLlvlLy are called oostetlc loblbltots
Intr|ns|c eff|cacy measure of response lnduced
C
S0
urug Lo lnduce 30 maxlmal response otqet ess poteot
pD
2
log
10
LC
30
lotqet mote poteot
ntagon|st blnd Lo recepLor buL ellclL no response hence blocklng agonlsL's 1herefore Lhey have aff|n|ty buL
no |ntr|ns|c eff|cacy for Lhe recepLor
9art|a| agon|sts fall Lo ellclL full responses eveo lf 100 teceptots occopleJ and obvlously block Lhe slLe for
full agonlsLs
angm|r dsorpt|on Isotherm %lqootes efflcocy ooy vlews offlolty)
and aL equlllbrlum




8 free recepLor concenLraLlon 8
L
u8
k
A
ls a concenLraLlon and quanLlfles offlolty lf A k
A
Lhen p wlll be 03 (30 of Lhe LoLal recepLor populaLlon
are bound) k
A
ls Lherefore Lhe concenLraLlon of drug requlred Lo occupy 30 of Lhe LoLal recepLor populaLlon
5moet k

ls o blqbet offlolty k
u
ls llgand relaLed nC1 recepLor relaLed
ln order Lo geL lL Lo vlew efflcacy Lhe varlablllLy ln response Arlens lnLroduced a consLanL Lo make up for Lhls
buL lL was sLlll a llnear equaLlon for a slgmoldal curve so a funcLlon of 'sLlmulus' was added Lo lL
( ( (

# #

#
#

(
( (
Some agonlsLs can be poLenL enough Lo ellclL maxlmal response wlLh only a small concenLraLlon of recepLor
slLe occupancy
Some recepLors have a consLanL basal level of sLlmulaLlon LhaL ls reduced by agonlsLs blndlng 1herefore
referred Lo as lovetse oqoolsts
8LCL1C8 PA8MACCLCC?
nlcoLlnlc ACP recepLors are ||gand gated |on channe|s eg aL Lhe neuromuscular [uncLlon nlcoLlne ls an
exogenous (exLernal Lo Lhe body) oqoolst Curare ls a competltlve oooJepootlzloq (doesn'L open Lhe channel)
blocker) and SuxameLhonlum ls a competltlve Jepootlzloq bocket (opens cannoL be degraded by
chollnesLerase's so lL depolarlzes Lhe membrane permanent|y)
Can also have oLher llgand gaLed lon channels whlch sLlll leL ln normal lons buL dlf llgands llke A1 blnd (Lo 2x
recepLor) noL only Lhls buL you geL lnhlblLory recepLors LhaL leL negaLlve lon ln CA8A ls a an example of a
llgand ln braln (neuroLransmlLLer") whlch blnds Lo (long name! recepLors) Lo leL Cl

ln
nuclear 8ecepLors
eg sLerolds (hormone) LnLer Lhe cyLosol blnd a recepLor prote|n floaLlng freely cause a conformaLlon
change enLers nucleus sLlmulaLes LranscrlpLlon
CC8s/ Ccoupled proLeln recepLors eq Moscotlolc Clc cb bloJs nlstomloe Ccl blstomloe
bloJs Jteoetqlc ootoJteooloe bloJs
Composed of proLelns ln seven Lransmembrane hellces C proLelncoupled recepLors are
acLlvaLed by an exLernal slgnal ln Lhe form of a llgand or oLher slgnal medlaLor
1he C

subunlL blnds whlch creaLes a conformaLlonal change ln Lhe recepLor


causlng acLlvaLlon of a C proLeln Cu leaves and C1 blnds C

dlssoclaLed from C

lurLher
effecL depends on Lhe Lype of C proLeln boLh or can blnd buL Lhe blnds Lo Lhe
effecLor and acLlvaLes lL Pydrolysls of Lhe C1 causes C

Lo dlssoclaLe from Lhe effecLor and


reblnd wlLh Lhe subunlL ulfferenL subunlLs can have dlfferenL lnhlblLory (C
l
) or
sLlmulaLory (C
s
) effecLs buL Lhey all lead Lo phosphorylaLlon
Many 9Cs are basa||y act|ve w|thot an agon|st w|th agon|st |ncreas|ng and |nverse agon|st decreas|ng
st|m|at|on
CC8s wlll evenLually desenslLlze by acLlvaLlng lndlscrlmlnaLe phosphorylaLlon proLelns LhaL phosphorylaLed
Lhe recepLors such LhaL g proLelns can'L couple Cr by loss of recepLors
A81 2
ln vitro ln LesL Lube in vivo ln organlsm
ln exam remember Lo converL Lhe response of drugs Lo percenL such LhaL ls comparlble before graphlng lL
1hen log
10
urug ploLed agalnsL Llnear graphs of drug response effecL ls a r shape loged s shape
C
S0
urug Lo lnduce 30 maxlmal response urugs poLency however ls also expressed as
pD
2
values log
10
urug Lo lnduce 30 maxlmal response
Intr|ns|c eff|cacy capaclLy Lo lnduce a response
ntagon|st blnds no response (has afflnlLy buL no lnLrlnslc efflcacy)
9art|a| gon|st blnds buL falls Lo ellclL full response or blocks responses lnduced by full agonlsLs aL Lhe
recepLor A sLrong parLlal agonlsL ls a sLrong agonlsL wlLh weak anLagonlsLlc acLlvlLy and vlce versa
Inverse gon|sts Some recepLors have basal acLlvlLy lnverse agonlsL reduce Lhls level of 'consLlLuLlve
acLlvaLlon' Lo a sLaLe of reduced response 1hls causes a negaLlve percenL change ln response lnv AgonlsL +
AnLagonlsL shlfLs Lhe negaLlve Lo Lhe rlghL LC
30
values can be Laken aL 30 or 30






1he law of mass acLlon sLaLes LhaL raLe of reacLlon ls proporLlonal Lo Lhe producL of Lhe concenLraLlons of Lhe
reacLanLs lL's Lhe assumpLlon used ln flrsL order derlvaLlons
8lg arrow preferenLlal way LhaL lL lles aL equlllbrlum 1he dlagram above shows LhaL lnverse agonlsL have a
preferenLlal afflnlLy Lo recepLors ln Lhelr resLlng sLaLe by blndlng Lo resLlng sLaLe lL causes acLlvaLed sLaLe Lo
shlfL Lo Lhe lefL Lo Lhe resLlng sLaLe Lherefore less response Lqually agonlsLs prefer Lo blnd Lo Lhe recepLor ln
lLs acLlvaLed sLaLe whlch pushes Lhe equlllbrlum Lowards Lhe acLlvaLed sLaLe as less free acLlvaLed sLaLes are
avallable n8 1he (compeLlLlve) anLagonlsL does noL affecL Lhe eq|||br|m [usL blocks affecL of elLher agonlsL
lL can LheoreLlcally dlsplace lnverse agonlsL and roise Lhe response
ntagon|sm
evers|b|e compet|t|ve antagon|sm arallel shlfL Lo S response curve Lo Lhe rlghL no reducLlon ln maxlmal
response lLs reverslble so ralslng agonlsL wlll dlsplace Lhe anLagonlsL (dlssoclaLlon levels are hlgh) and resLore
occupancy and response
Irrevers|b|e compet|t|ve antagon|sm osslble 8educed response ShlfL Lo rlghL AnLagonlsL dlssoclaLes very
sowy from Lhe recepLor Lherefore more agonlsL doesn'L dlsplace very much Lherefore sma|| shlfL Lo rlghL lL
lowers Lhe maxlmum response as lL blocks recepLor slLes however ls Lhere ls noL enough anLagonlsL Lo block
Lhe # of recepLors needed for agonlsm (can be 3 lf poLenL agonlsL) Lhen lL can !uS1 shlfL Lo rlghL no reduce
ln max
ff|n|ty ls Lhermodynamlc Langmulr AdsorpLlon lsoLherm made a blndlng slLe Lheory adapLed Lo
lracLlon of all recepLors bound (p)
|AR]
|R
t
]
=
|A]
|A]+ K
c

Where A8 of drugrecepLor complex 8
L
1oLal of recepLor k
A
u8uC/8LCL1C8 dlssoclaLlon consLanL (slmllar
Lo k
u
LlCAnu 8lnulnC dlssoclaLlon consLanL) A conc of drug
k
a
quanLlfles afflnlLy lf A k
a
Lhen 30 of LoLal recepLors bound Smaller k
a
more Lo lefL more Lo A8 more afflnlLy

-on compet|t|ve antagon|sm 8locks chaln of evenLs LhaL lead Lo response eg does noL acL on Lhe same
recepLor as Lhe agonlsL buL has Lhe opposlLe effecL
Chem|ca| antagon|sm 1wo drugs comblne ln soluLlon such LhaL Lhe effecL of Lhe acLlve drug ls losL
9harmacok|net|c antagon|sm Where one drug reduced Lhe conc of an acLlve drug aL lLs slLe of acLlon eg a
drug whlch ellclLs a change ln meLabollc raLe or absorpLlon
9hys|o|og|ca| antagon|sm lnLeracLlon of Lwo drugs whose opposlng acLlons cancel each oLher eg Ach vs nA
harmacologlcally lL ls useful Lo know Lhe doses needed of agonlsL Lo evoke a response wlLh respecL Lo
anLagonlsLs 1he dose raLlo glves Lhls lnfo lL ls Lhe raLlo by whlch Lhe agonlsL concenLraLlon ls lncreased |n the
presence of revers|b|e compet|t|ve antagon|st Lo resLore Lhe glven response (eg LC
30
)
uose raLlo
|X]
|X
A
]
= +
|B]
K
B

Where 8 anLagonlsL conc k
8
anLagonlsL dlssoclaLlon consLanL
x dose of agonlsL Lo evoke Lhe magnlLude of response (eg LC
30
) ln Lhe absence of anLagonlsL
x
A
dose of agonlsL Lo evoke Lhe magnlLude of response ln Lhe presence of anLagonlsL

Sch||d 9|ot sed to determ|ne potency from drg rat|o
1ake logs of Lhe above
? 1x + c (lf 1 Lhen lL lmplles lL ls non compeLlLlve)
u8 AgonlsL / AgonlsL wlLh anLagonlsL

y lnLercepL 0 log(u81)
1herefore u8 1 1 and u8 2 1hls mean LhaL Lhe anLagonlsL aL Lhe y lnLercepL ls Lwlce Lhe agonlsL
requlred Lo ellclL Lhe same response as Lhe agonlsL alone and ls equal Lo Lhe equlllbrlum dlssoclaLlon consLanL
(k
8
) of Lhe anLagonlsLrecepLor complex k
8
ls an lndlcaLor of antagon|sm potency
[Antagonist] uM
Agonist EC
50
uM
DR Log(DR-1)
None 0.019 -------------- --------------
0.0015 0.047 2.47 0.168
0.003 0.079 4.158 0.499
0.006 0.154 8.105 0.852
0.012 0.28 14.737 1.138
)

# 4 4 4
pA
2
value of an anLagonlsL ls log8 when u82 k
8
8 Larger pA
2
ls more poLenL

evers|b|e Inh|b|t|on
O ln compet|t|ve |nh|b|t|on |ncrease apparent km Lhe
subsLraLe and lnhlblLor cannoL blnd Lo Lhe enzyme aL Lhe
same Llme as shown ln Lhe flgure on Lhe lefL 1hls usually
resulLs from Lhe lnhlblLor havlng an afflnlLy for Lhe acLlve slLe
of an enzyme where Lhe subsLraLe also blnds Lhe subsLraLe
and lnhlblLor compete for access Lo Lhe enzymes acLlve slLe
1hls Lype of lnhlblLlon can be overcome by sufflclenLly hlgh
concenLraLlons of subsLraLe le by ouLcompeLlng Lhe
lnhlblLor CompeLlLlve lnhlblLors are ofLen slmllar ln sLrucLure
Lo Lhe real subsLraLe
O ncompet|t|ve |nh|b|t|on 8oth max|mm ve|oc|ty
(Vmax) and b|nd|ng eff|c|ency (km) decrease Lhe lnhlblLor
blnds only Lo Lhe subsLraLeenzyme complex lL should noL be
confused wlLh noncompeLlLlve lnhlblLors
O ln m|xed |nh|b|t|on]M|xed Compet|t|ve |ncrease apparent
k
m
and decrase apparent V
max
1he lnhlblLor can blnd Lo Lhe
enzyme aL Lhe same Llme as Lhe enzymes subsLraLe
Powever Lhe blndlng of Lhe lnhlblLor affecLs Lhe blndlng of
Lhe subsLraLe and vlce versa 1hls Lype of lnhlblLlon can be
reduced buL noL overcome by lncreaslng concenLraLlons of
subsLraLe AlLhough lL ls posslble for mlxedLype lnhlblLors Lo
blnd ln Lhe acLlve slLe Lhls Lype of lnhlblLlon generally resulLs
from an allosLerlc effecL where Lhe lnhlblLor blnds Lo a
dlfferenL slLe on an enzyme lnhlblLor blndlng Lo Lhls
allosLerlc slLe changes Lhe conformaLlon (le LerLlary
sLrucLure or Lhreedlmenslonal shape) of Lhe enzyme so LhaL
Lhe afflnlLy of Lhe subsLraLe for Lhe acLlve slLe ls reduced
O -oncompet|t|ve |nh|b|t|on decrease apparent V
max
a
form of mlxed lnhlblLlon where Lhe blndlng of Lhe lnhlblLor Lo
Lhe enzyme reduces lLs acLlvlLy buL does noL affecL Lhe
blndlng of subsLraLe As a resulL Lhe exLenL of lnhlblLlon
depends only on Lhe concenLraLlon of Lhe lnhlblLor
ermlsslon ls granLed Lo copy dlsLrlbuLe and/or modlfy Lhls documenL under Lhe Lerms of Lhe -D Iree
Docmentat|on |cense verslon 12 or any laLer verslon publlshed by Lhe lree SofLware loundaLlon wlLh no
lnvarlanL SecLlons no lronLCover 1exLs and no 8ackCover 1exLs





nuCLLlC ACluS
nucleoLldes phosphorelaLed nucleosldes are Lhe same buL noL phosphorylaLed 2 P bond 3 P bond
A Cong 1u Clang
una 8lghL handed hellx
ueamlnaLlon occurs sponLaneously ln Lhe cell when cyLoslne deamlnaLe lL forms uracll and hence can be
recognlzed as unnaLural and repalred All Lhe bases deamlnaLe Lo varlous producLs excepL 1hymlne whlch
doesn'L lf uracll were Lhe fourLh unA base lL would be lndlsLlngulshable by Lhe cell form Lhe deamlnaLlon
producL of cyLoslne
'1he CenLral dogma' ls Lhe ldea LhaL lnfo ln Lhe unA codes for proLelns
8nA has oxyrlbose and uracll unA has a P lnsLead of CP as lL makes lL more reslsLanL Lo enzymaLlc and
hydrolyLlc degradaLlon and makes unA more sLable 8nA ls noL deslrably sLable for long Lerm
1wo blosynLheLlc paLhways Lo make unA sovoqe and Je oovo (from scraLch) anlmal braln cells cannoL Lo de
novo and lL Lakes far more energy AA's CC2 nP2 8lbosehosphaLe can be used for Salvage paLhway
unA aprox 2nm wlde base palrs 034nm aparL verLlcally 34nm for a hellcal Lerm Lherefore 10 bp per Lurn
S|mp||f|ed D- rep||cat|on
8equlres a prlmer Pellcase unwlnds Lhe duplex flrsL Lhls exposes slngle sLranded unA so Lo sLop lL
compllmenLary base palrlng wlLh lLself and formlng halrpln loops slngle sLranded blndlng proLelns blnd
8epllcaLlon ls always from Lhe 3' Lo Lhe 3' end of Lhe parenL duplex Llgase [olns Lhe Casakl fragmenLs










Mlnlmlzlng Lrror ln unA
1 Lrrors occur ln repllcaLlon eg ln a cerLaln shorLllved LauLomerlzed form cyLoslne can palr wlLh adenlne
1o mlnlmlze Lhls D- po|ymerase 1 sLarLs on a pr|mer on Lhe unA and moves along lL lL forms Lhe
Lagglng/Leadlng sLrang when lL meeLs a cocked up blL whlch sLlcks ouL lL chops lL up wlLh 'endonuclease'
acLlvlLy allowlng repllcaLlon Lo conLlnue normally
2 MlsmaLch 8epalr ls where lncorrecLly palred bases are removed ln bacLerla old (parenL) sequences
become meLhylaLed whllsL new (daughLer) unA ls noL once a daughLer sLrand has been ldenLlfled
lncorrecL bases can be repalred respecLlvely
1he repllcaLlon form shown ln Lhe above dlagram orlglnaLes ln one of more polnLs wlLh a parLlcular sequence
Lo recognlze lL unA Pellcase ls lnvolved ln openlng lL
uurlng transcr|pt|on the m- mo|ec|e ls synLheslsed by a process slmllar Lo unA repllcaLlon excepL LhaL
W Lhe enzyme ls - po|ymerase
W 8nA polymerase does not req|re a pr|mer
W 8nA polymerase does not proof read Lhe synLhesls
W Lhe sugars ln Lhe nuclelc acld backbone are r|bose not deoxyr|bose
W Lhe four bases used are adenlne guanlne cyLoslne and uracll (not thym|ne)
W unllke unA repllcaLlon m8nA synLhesls sLarLs aL many places on Lhe unA sequence and sLops aL
predeLermlned places (done ln llLLle chops of proLeln place where lL sLarLs ls deLermlned by a
romoter lf Lwo or more genes share a promoLer Lhen Lhls group ls called an oeron
W unllke unA synLhesls when synLhesls of a m8nA molecule ls compleLe lL ls released from Lhe
LemplaLe as a slngle sLranded molecule noLe LhaL ||ke unA synLhesls 8nA synLhesls Lakes place ln a
S' to 3' d|rect|on (re|at|ve to |tse|f)
W Cod|ng strand and @emp|ate Strand are Lhe keywords for Lhe Lwo sldes of Lhe unA
W Stop s|gna| for - po|ymerase |s a rn of @'s fo||owed by a C ha|rp|n |oop
@rans|at|on Aminoacyl-tRNA synthetases are responsible for attaching the correct amino acids
to a specific tRNA.

AUG triplet codes unambiguously for methionine, which is the start signal for
translation.

3 Stop codes for trans|at|on D D D

(1o help learn Lhls no C's are lnvolved D agmenLlng sLarL
DnlverslLy of mlno clds uAC/CA)

Codons are noL degeneraLe buL Lhe unA bases are Codons have 3 nucleoLldes on Lhem


D|fferences |n 9rote|n Synthes|s

9rokaryot|c Ce||s karyot|c Ce||s
m8nA may code for several proLelns (eg relaLed
proLelns ln an operon) (polyclsLronlc)
m8nA only codes for one proLeln (monoclsLronlc)
1ranslaLlon and LranscrlpLlon close ln space and Llme
parL can be compleLely Lranscrlbed whlle 3' end of
m8nA sLlll aLLached
SeparaLed ln Llme Space LranscrlpLlon and 8nA
processlng ln nuclear envelope 8nA LranslaLlon on
8L8
uue Lo above polnL noL llkely Lo be modlfled before
LranslaLlon
m8nA ofLen processed before LranslaLlon 'Spllclng' ls
done where lnLrons are cuL ouL and re[olned wlLh
exons ln dlfferenL places Lhls makes subLly dlf
proLelns