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PharmaceuticalBiochemistry, 34lC NAME &^o*Vierr{. ffotn

Exam L, Dr. Whitman, L00pts (Print legibly)
October7.2003 (DO NOT PUT YOUR SSNON THrS EXAM)

+ " -{ ; G+i
-
PARTI - Trueor False(circleT or F) (2ptseach) - 5 t_
/rn) \
z] _
1 ' '(y l:v
l:# ?i"f*,[]ffiierlifiJ acid
isabout
I to
tryor',:1,".'^:;:';"il.,ffi"'.
q, L'S * *l 'i lan "' i * t:*-
"$
tfrr
- o,5f = 1 r, , {
tflY

Q':l = N-
.4. I l'rft
2. (T ) F At physiologicalpH Q.$ aIl20 commonamino acidshaveboth positiveand negarive
*r,?. pts'' acJ . r- 4-- tutrru*
ChafgeS. I fr)
ry L "0i1, ' 5 1* d'""""T' C) U/-'
-. f--\
3. T /(F ) t\".oxygen binding curveof normaladulthemoglobincouldbe shiftedro rhprigiifUy
\'/ mixing the adulthemoglobinwifr-EtaiTeffioffiin.- V
W T /O Thesubstitution
of y{ine-6 for glutamate-6 of hemoglobin is a change in
pnmary structure,which causesan incJeaSe
in rbin solubiliW.
5 ." r 0 ThepK"valuesfor asparticacidare2.0,4.0and-10.0.Hence,thepI is 7.0.
r,/
@ --*:--.-"5ffio -j1-"--:,
"l' ...-...*--"--... :.j
.,',., I L)
l--" *l
. 4t

? L' + fl'^ - &r e{

'".*-*1.-*-*-
:. i d @ # g
.-3
p f = L
t - *

f \
6. T { F )The following m{e*r{es aredissolvedseparateiyinto bufferedsolutionsat pH 11. The
\-/ chargedspeciesofQgpmoleculeswill predominate in this solution.

?H ,-] o
cH,
l * i l . H
CH3- O- C- CH2CH2CH,3 I\rH3
f-cozH
H

PKa= 4'0 PKa=9'5

 7 . 7

es*(-
$o_

'0, The following datawerecollectedfor an enzyme-catdyzed

reaction.
S.pm
t.25
r-T]r.]-)
v. plWmin
14
35e.
;*6f
\-4d 56
{-tc
100 66
200 69
1000 r{*tea
f"E
Thev,'* for the reactionis -70 ui\zllminandtheK,, is about 10 pM.
, n #
g'rft)Theimmediateeffectsofhyperverrtiiatngarffiincarbondioxideandcarbonicacid
\J concentrations. -
A ,ry
10. I F Thereacrion velocityis eqlalro0.33V,"* when[S] = 0.5K..
^
f 4
U vo t*-lt .-*
"ll ..rlt-
'5a) ,/-_. / r\
/*^: !*I
K* +(s) ,/
v,*fT{ ! i { v^r,

11. T 1000sec-'anda molecrrlar

ygightof_21,500
g/moles.The\r-* for
W Tt{t"" las
fthereactionis - 1k*o=
0.93;rmole/sec
when0.1TL of a0.2mglml-enzym6
,H is present.
-3 -1u
\l-aF
J*-
I'n'. f{
X
.ZXto3
#x .l^L = 1 , 3Vl 0 r " , k
Kcrt" e Ltr€va r""L :

-4
? t t l
rq'le q ?.3 XZo /1.J<
Q,3 Yt o
rA=
L

'
tj' 2 &* =li;q
K.or =
r
 An enzymeprocesses subsrateA andsubstrate B. V/ith substrate
A, theho is 25 sec-'and
theK. is 0.1mM andwith substrate B, thek.u,is100sec-tandtheK^is 1 rifu. SubskateB
is thebettersubsffate.
'k.^r ':
' -V
- ,i ^..*i
-*s:1"*- ..-- q..r|t'
'> 75o e
I

B
13.
ro The V** for a reactionis 170 mmoles/sec.In with a
4 = 5'iiM, thev**d66G?3Es$g-nificantly.
t-*--::;:f*

r+@n If two or morepolypeptidechainsarejoingdby Nan

exampleof quaternary
-- structures. ,{"*. .. ,

rs$rr TheT s,f1feof l9q: cell anemiahemoglobinis proneto polymerizationandprecipitation.

Part IL Multiple Choice(no correctanswer,one,two or morecorect answers)(4 pts each)

1.6. The ability of hemoglobin to serve as an effective transporter of oxygen and carbon dioxide is/are
explainedby which of the following property(ies)?
/ ,-'/
AnJvtt( .-{i.r.Hemoglobin
.,^ r' bindsoxyqel.Eoreti.qhtlyF*rrygl*in, especially atlow oxygenpressures.
'['Io ,B'i'
'-€1'... Hemoglobin,like myoglobin,
readiiyswitchesbetweentwo conformations.
Increaiedconcentffi=of .*Uon hioiide increasetheaUifiryoirret*gfoUin to biafl.oiygen.
,Dl' Hemoglobinusesferric iro+ ffi#),to 6ind oxygenwhile rnyoglobinusEsferroui#; G't?-).
17. Which of thefollowingstatements
is/areTRUE aboutthecorresponding
aminoacid?

"l

q _Lo.v
uV- L4' /@
I

a *L* 0
I J
*--.'::::) * !
t / { J}
lil
@(PP*:-
J l i s- f k."- r { r
\ r--.
\9

o
 of the
for a common amino acid' Which
1 8 . The graph below. shows a titration curve
statementsabout rne graph is/are TRUE?
4 A I
It l l I
I
t l I
t l
- l - - - - - - l 1 -
t l
I I I
I

4n
; D r
t , f
Ii t f - ' r t '
u'r'
1 l
l ,t,
'-'
j
l, '
l! ----' '

0 .0

-K, ffi;;il;i"tdu.ia it tullv ionizedatpointB' cre..

f. ilffi'H,ffi ;?#o#;ffi ,?";ilaandcon3ug-ate_bSppdiiareequar.
(*)

ffi

renders
1 9 . Trypsinhassix disulfidebonds. Treatmentof trypsinwtt.h8 M ureaand2-mercaptoethanol returns tulI
g with dif bxfosure
it inactive. Removarof borh tvl ure;;;; i:#;*pJo"tr*ffifung
theseobservationll -r,*.-..
activity. What.o"Jotiont migtrtbe madefrom
tertiary
becauseof changesinJfilnery] secondary'and
',8- tneinactive enzymelikely result
-K
into
sidechains
pairsof cysteine
airoxidario'
iffi"Jil;:re conditions, Soo,ffi;"onverts
..{-/
'; iit"rrii" u""at. for conect folding'
( C) The amino acid sequencecontaigsall the information
V "
p"t"i"i"ri"n of trypsinis i{t@ib}'
-'{-*-**t""
,{

2 has"5*:l01mM Whatcanbeconcludedabout
20. Enzymet hasaK,of l-nYI *hit""'i'yme
enzymesl andZ?
K''Enzymelwillincreasetheactivationenergyofitsreactionwhileenzytne2willshiftthe
'r* ;;;-ilib""* constantto favorproductformation' than
"Enzyme concentrations
B;* 2 would becomesaturat;Jwith substrateat lg!:.*-u":.!,ge
."{
-enzymeL. 2'
il?ffi J wiil haveahigherk ",value1\anenzvme Z *Vt' only enzyme1 will increase'its
#;;^i';illo
increaset
If the substrateconcentr*ation
reaction rate signific-antlY.
V"*^.. +

l''tr f, r^
v --'::t ''/' ' t
\ '
'
V t -
N f ^'
-
- ;-/-'" t
I ., -a {,"."
.. '
 21. The binding of oxygen to normal adult hemogiobinis iqgpaggdby:

'/K increasedconcentrationsof 2,3-BPG.

G) the binding of oxygen to deoxyhemoglobin.
p _ncreased
eO, teve'is.
)fncreased pH.'
22. The o-helix
*-'i_.. structuretypicaily has which of the following characteristic(s)?
.. ..

" $':The structurecanconsistsof one,two, or threepolypeptide

^ chains.
FJo , H" The structureis generallyrich in tryptophanresiau&.
f/r' inhvdrogen
bonding'
Anr 4 +i:TJJ1tr"0"ffi1"'flH,?;:xti*:*aG
23. Which of the following statementsis/areTRUE aboutthe cycle peptide shownbelow?

Pro - Ser

l l \| ':' \/
Gly His ---> iip: "l<-,
l'
( +l
.- ,.rl)
t--

7V,
-rn- l
Cys Glu -
l t'L"
L'l
\\\
" ,
L.{i
!

r^
)

- I l,-
-.

l
Val - Thr
l
-^Xllthas five lonlzaDle
{. ..,Ilnas nve ionizablelunctlonal
functionalgroups.
pro ,W_ AtpH 12.0,the
' net chargeis +-0;L z"v
"nff Hydroly-sis
-l-'z

of .the peptidgbdffi-betweenGly and Cys would resulr in a peptidewit6

f rl*,a( _ chemicallySrnflarproperties(but ring opened).
,.V' The order oT-lfi6aniind acidsin ttrecyitii peptideir l***SS for its function.
a^
Which of the following statements
is/areTRUE?

.,A:"' Phenylketonuria
,n^-\
(PKU) resultsin ._
low levelsof phenylalanine andhigh leveisof tyrosine(in
blood andurine).
(3{nt overdoseof Tylenolcanleadto liver toxicitydueto glutathione depletion.
<p,t:par.oxyp44: andhydroxy@E arecriticalf9r theformatjo*qf thecollagentriplehelix.
andotheraminoacidiwith smallsidechains,lke {fp,are
"-HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH key c"ompoientsof the
collagentriplehelix *ffi,*.

25' A7Z-y.eatol-dmaleentersthe emerg-encyroombecausehe is in respiratorydistress(difficutty

breathing). His blood pH is 7.1. Which of the following statemeitsis/areTRUE abouthis
situation?

R
.F
The ratio of bicarbonateto carbonic acid in the blood is about5 to 1 (assumes
Ih9 nalient.islikely eiperiencingmetabplic acidosis.
\ -- - ----- --r

His carbonic acid levels have increasedfrom thoseobservedunderhealthy conditions.

apKaof 6.4).
'
If the situation continuesfor severalAafr-frewill likely retain bicarbonate. ?7 , "' r:l'1-r11''

0.'{ '( -'*

I 2

d l,l r f k + r . , ] { ! "t u . { o *} I
f
fr ' u-"
! {
'tft
Yll'
F:,r-
t

Part lil. Short Answer (For full credit show your work)

26. Two polypeptidechainscontaining10aminoeachfonn a two strandanti-parailelB-sheet.

(a) Dt"T a ribbon diagramshowingthe directionof eachstrandin the B-sheet.(2pts)

{ft-t"r*J

a*ii;es

(b) S/hut arethe-trr{naryinter4glig{lgresponsiblefor stabilizationof this strucure and providea

definition.(1p0
. F 6'fr'-'rto^s d '(Eos;{o J4^Y2/ f'"f 5
€h't1'e***" i''u* "1oar " l"'l<- "
- - p'ft'"'fr"' -(ip'11-'/l''-' froufs
flral^ nl,rl,. 1{f*a.rtt^s
4 ' * - - " v ' ' - t ; ? v
Y
/ Ltq/"Th"b;.)
I ll
,*2 il/'!- n*/ elail,' *J,
Hy/,,"5*^bo^/i^s /
'nifay^ 4-h * '^.L\
&.s Ar17e*
, l'fr
\
I
I
I

(c) Dpw the primary interactionqthat stabilizethis structure(enoughso that I know you know
whatyou aretalking about). (2pt)

tt sf.:Uhf
C'n5le
i -(qo!) l N hnh; po'ulh I
H + C aa ' J . ; 9 t # *
I b -st@'
N
D
I

6
 (r, *Itr-fr{ *1" -To-Vol^ Gh^ al- (r" -Lys
5n,,'Gl,^

28. The structureof penicillinis shownbelow.

(a) Whattypeof inhibitoris penicillin? (lpt)

t l

II !"'vtrt)b(L
I

(b) What are the consequencesof its action? (2pt)

q* W
$;^ls h {\+ enla * ,'n w*":fo'i
-r
\
l1 ^L,b;ls 4i* bo&rk* #b koke 6*{l **(l
ll
u
'" 'o -fl-r**
I+ Li^/, *t 4l^* D-ofo * b -c 1," 6r.n**' t tA uV e
I
t

te.<*SlLa-
b7 lat uolcnf
4 S rac{- nn €+z1n&
/ --**e *-" -rJ.^*. ooo
GA"& r
 (c) Showthe mechanisrnof actionfor penicillin. (2pt)

f1 f*6ej
re 'fL-r* .6.
rc
*r bu^l
f. r' ! .r'i t u l
I
(t'1711ft& 7eni till ,- 'Ja,ns 4- t:
J

df- *fl*is seJ**$ 'fx--.*

4l;' ,,puT* / in*Ji r",:t) y

{-n,Zt1M.

29. g13:ilEhas thefollowingaminoacidcomposition;Ala, Arg,2 Asp, 2 Gla,3 Gly, Iru, and 3 Val.
After+aitial hydrolysis,the following peptideswere isolatedand their sequencedeterminedby
Edmandesradation.

l ! IrLLr-\JrJ-ru5
**-. ...

(a) Whatis the structureof theoriginal13-mer?(3pts)

lnu-Gl1-A'1
- * T - 6 U , 'V* ^ {
V h-lA r f f * V ^ {

properties.(zpt)
for its characteristic
(b) Draw a peptidebondandindicatewhatis responsible
oo ^\
l),t
_al l / *
,[.
r, r ' ,
hJ*
t
--_>
<F
_
*L=,V fi
4 t -41,"r*
rt ,
(2 ) {l-rt donbt_ .ooJ T"*^
4Uz- rz''o /1'-r,. f ,, - { r * \ .t
U 1a1at'k i
r-;dqiclAll ! cc"*'f,
bo^J rT$

o;^.""^'"tr,
J J
fef'fu
'fuPh''tr'z
bt 'ls A*r ,-,l"*]t ,i;
f't^.L wlu
Y3!:"::^'
Prir*.= rs9.*{.184*
 (a) Why? (2pt)
f q;b a-ho;^ f"5 ''"i *x-
Tl"ir ctrstrq"bl( +1& 1
1'"*f o^- ir1 f u;^ ( e' =3-"*-)
.
/*l l;ols 1. 47,. 7-6'-fiu'c- sik
it
.f1^t^'bi(", '-+'

(b) Whattypeof inhibitionwouldyou expectfor benzamidine?(lpt)

li " *
T^ tr',;b;
C.uo 6o-lrr*

(c) Draw a Lineweaver Burke plot for this type of inhibition clearly identifying the inhibited and
"L.)i
,'-.i-Lj1-.i+^'l
uninhibitedlines.l.i-^-
(2pt)
/a-+\ r ar X r
.xr x I
'^L'hf'" t',lbI*
"'rn"o
"t $,^ -
/*Y 1,,1;Li*n
J Kr^
V sloT<

L
Vrn,ny

\ -y(*
31,. (a) Describethe Bohr effect. (1pt) 5

ul
0 z ^t-[[[[[[[[[[[[[[[[::*
ol*f, .dt (nr, co-)
Hb ficLs uf *
\ f{,
.

i r*T
l

1iP5**d5 &*i #*;s d* q

HI yi*t.s tlf {*\ * L . )
%

\
 {

-;;;;
(b) WhatisthemolecularbasisfortheBohreffect?(2pts)
! i*
.t .}-Ll'
!,*Tfel&#"'&-c"s*'*i&* a*of sl,'rhl'e'*ib5
-T-r+#f- ."';;S ry -is -a'{
$qsqr,I' ;-P
jl-';- td* p;**ml '16 ia $u**
rt 1q,.ant'xJ*#
tustqr&e oL
Il
i: *tqbt*'Jd $.1,**';J' *'J* ^l:*'f ' Til; 4;'*
gu,wx;.11
,1 f* &* elr;6Pedtrd6 I
I
!
f&n A$F
#ryt2*4* -'.f :
.ud-/&
n L^ s *s-[*{e*,:j} cta*{"at,on*,fi'* Y
ea"sias'i+ f if,f-
A *&.,r-Ptt*# 6*o{**"*
o*y pn*&i,, n*a;*' " *
4L'"-- " (#*',f} ^:.*'}f1
lL'- ls* a*I?n ti"ls )
v+f;^<. t-tuv'5 oJ J- 6x19e^ 6;^"di"3 '
-s t"i- s',*l,k-ut
'fb u# ' &'*
!..{qblc
*' l6x35e^"
p*r r€-

in Hemoglobin?(2pts)
of conformations
(c) Whatis the molecularbasisfor interconversion
*3J*ho* '{or*
d-* on1A,**'
a*1Jrnrc'**si*) fl.*
6i^nt\ d
sk*fr u'a*
g laa *r
'/t 4n
' - l''k*
./o *hr*ny ,/r*r* d*r*o
l*prt d.,..* o-,L;ck i5 *iW**{w.{
-f [; r '-M lnix{"d^*a
p*lls &''1'
#'' i't (a',f artt*31b^
Shii;*
#d* *t**'s;15;+
d.W ;4,4r
\

"I have neither participatedin nopuilnessed acadertricdishonestypertainingto this

" (signature)
examinationor assignment.

1,0;