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PharmaceuticalBiochemistry, 341,C
100prs
.3:il1*il?#rman, legibly)

PART I - True or False (circle T or F) (2 pts each)

i. T lV The.a-carbonof an aminoacid hasfour groupsattachedto it and is part of the planarand

rigid structureof thepeptidebond.

?, , Lysine-86-inthe btryl.pr_ote4,-liochemstudent,
has a pK. of 9.0. At pH 6.0, the ratio of
conjugate
baseto acidis 1 to 1000.

1,@'
'':',5\
F An increasein the 2,3 BPG concentration
resultsin a higherProvaluefor hemoglobin.
4,wl F The common20 amino acid all haveat leasttwo buffering regions while some have three
bufferingregions.
F At pH 7.0,glutamatehasa netnegativecharge.

F Startingwith thepeptidebond,a proteincontainsatomsconnected

in the orderC-N-C-C.
7,',@ F Replacementof cysteinewith an alaninein a proteinis likely to havea moredrastic:stnrcture
effectthanis thereplacementof a lysinewittr-anarginine.
+ ' ] .

8. f Lg ) An enzymehasa V,"* of 1.0p.moles/min and'aI( of 0.2mM. At a substrateconcenffation

of 0.1 mM, therateof thereactionis 0.5 pmole/min.
J
g. T t@ Fetalhemoglobinbindsoxygenand more tightly than adult hemoglobin.
I
10. T /Uq/ Both thecollagentriple helix andthecr-helixarerich in prolineandglycineresidues.
1 1 . T /C Ala leu and Phe are threeamino acidslikely to be found on the outsideof a giobular
v protein.

12. T lY The diisopropylphosphofluoridate

(DlPF)-inactivated
trypsinlookslike A.
QH"

6H:\
>rP-o1
r l l
t P, zcHz
'cH'
Y""'
J
"{r-,

n l
ov
-/ [\
-//
't_
\-{^ DIPF

Z \ A
13. T /(-F)m"Jr{tosyi-phenylalanine chloromethylketone (TPCK)-inactivated
chymotrypsinlooks
- like B.

H P
'
'Y ..cl
R N -,r-[-.""6i-]
t
t- f-f"-*o
I Phe
i l ' L / -L
5x,^
\ r?cr(
 a ^ , - _

Both hemoglobinar
oxvsen e---"' qv vt bv lotsof q-heiices
oxygen ro ferrous
to ferrous i.": lll;f1""*:=:lrrterized
o rr. 't' ,4:\
'U
inrn rn their heme portions. and the binding of
Jlclilng of Hbs occursin the
T statebecause
theconcentration
of 2,3BpGdecreases.
Part II. Multiple Choice(no
correctanswer,one,two or
morecorrectanswers)(4 pts
16. each)
yti:i."^^*,":t"* staremenrs
is/areTRI'Eregarding
enzymes?
A. catalyze
reacdonsbecausethey lower
H:il":Ptively
reaction. the equilibrium constant
Thgv"* for the*"..,j::.11:lrined rorqrtt for the
IUI'

^,f,*r& #i"t"j?::}:?n:xft
#'":r,,',TH:*i{:;::??r:f
li'*:,il:tT:"Ht*'#*:"#l
f;::",,iTb-ttraterconcentrations,
kinetics (i.e, d6;|f,;i!ffi;,ff#rc
1l9
Ihe amino acia".,rlrtriinc
(reached)
rh"';;;" or
rr.^r..-^.-.
whenatlof tht
or an
an enzyme
enzwne"*i,Yy^\l
: concentration).
i:-in the.EScomplex.
rvo agru Uf0el

ffifrHil::fis"*jl*x
theprimary
r.qoJn.."ffi 3f
&ffiffi::i,i
!?1ffi:l:lilhr,,.
must bec,ose
roone
anorher
in

20. Penicillin:

-4' is a competitiveinhibitor
" (D of atranspepti4ase
involvedintacterial ceil war
formsaioudtniffi'*ril'J.."rp.itid*;i#Jru.ain synthesis.
u-acteriJc-e-tt
wa' synrhesis.
ffi't'*ffili;*
: is incdmo 1#*r6i&hd;;il;;" skand which
ispar:tialry
responsibre
D. rorirs
thebacterial
cellwa]l,whichweakens
il rt;iJ#i1'::iii: thecelrwan,andultimarery
resurts
n 1
/.t,

fiH:t?'l;:?":iJ#,'"!:1n:H*:,,:i::rHi*'e:9,rbonrinribrinogen
;;Jll',ffih#f"ro"?*:;1f,
f :n,"tr,.iotio*idffi ,fril,?T
It is a serine protease.

Xi:*:::**: F1l :nqi:tingofAsp,HisandSer.

jilffi:_il;?:,.t"llsffj
*,x*r*:::.*,
catalyzedhydrolysis. substratein the courseof
the thrombin_
 A histidineresidueand the oxyanionhole activatea watermoleculefor attackof the acyl
intermediate.
Thecompoundshownbelowis likely to inhibit thrombin.

R-T-CH2-C-CH2C1
fl
H

22. Th,efollowing data was collectedfor the hydrolysisof nvo small peptidesby elastase.ft. "3"
lndlcatesthesiteof cleavage

Substrate K_ (mM) k"", (sec-r) kc*t t 1".^

G
(1) Ala-ho-Ala] Cty 4 30 t'{
(2) AIa-Pro-AIafAIa | 40 110
(3) Pro-Ala-Alaf Phe 0.5 2 t{

which of the roilo*ing statementsls/are

TRIIE regardingthesedata?

*[. A Peptide#3 is the bestsubstratefor elastase.

NJ" B . The dataindicatethatelEstaseprefers-asubstratewittr a largehydrophobicresidue(e.g.,phe)
o
$e2
t..
on theCterminal sideof thecleavedbond.
c . Peptide#1 is the poorestsubstrate.
D . lase-don this data,elastase
doesnot like substrates
with Gly or Ala on the C-terminalsideof
thecleavedbond.
23. Considerthe following buffers.

#1 0.01M Na,IIPO,and0.01M NaIlpO,-

#2 0.1 M Na,HPOninO O.t M NaI{,p6,+
#3 1 M NqIiPOu a:nd1 M NaIITPO;

which of the following statements

is/areTRIjE regardingthesedata?
NaHrPOoistheconjugate
6 basefor all threebuffers.
Buffer #3 hasthe highestbufferingcapacity.

6 Buffer#3 hasthehlghestpH(pKi=i.Zl.
All threebuffersare!ffectiveiir UiepH iangeof 6.2to g.2.
24. Which of the following propertiesis/arecommonto both a-helicesandB-sheets?

S. Ifey arestabilizedby hydrogenbondingbetweenaminoacidsidechains.

I They aredisruptedby big bulky groupsluchasrryptophan.
g 9ly ir generallyfoundat everyitrirdrbsidue.
tD.) Revelsr.bledenaturationby giranidinehydrochlorideprovidesevidencethat the information
specifyingtheseelementsis foundin theaminoacidsequence.
25. Thebindingof oxygento Hemoglobinis:

@ increased(o, binds more strongly) by a decreasein H* concentration.

B . cooperativeand resultsin a hyperbolic curve.
@ decreasedby an increasein the CO" concentrations.
D . increasedby an increasein the 2,3-BPG concentration.
\-
 Part III. Short Answer (For full creditshowyour work)

26. (a) Showthedigestionproductsfor thefollowingpeptideaftertreatmentwith trypsin.(2pts)

,a
arg$et
a-tvt"rl-vrhvrfu
er-Gly-rhr-rie-rrp-Met-s
er-nrgljrys
-$
I f l|

(b) Whatis thestructuralbasisfor Trypsin'sspecificity?(2pts)

M
1 f i e ' f|L

?
2 o , "' aok)
trtg'(ur-
-fn,,,"- ""
v r a'r.:i'.rio'* o,ul
-
o'\
t
b-')rl
rr

t^u*
27. If 10mLof 0.01Mlactateis addedro10mL of0.1 Mlacric id (shownbeiow,pK. = 3.86). What
*\-^.n^)
will bethe pH of theresultingsolution?(4pts) 0'

?'
cH:-f-co2H
I
H
* .t",
?h=fl...
O. t? | L'( g,o I r.t&a {"-,L^-k
f*
- 0..loot rn,rL'
F

l- J, Nt + [',\ o.oof ltt

[ -
h* G,,u{
O,oot '^Jtr
'* , u
6 , o t L O' I v^-x.' ^
F.

L- l. vt - r

lo.l**, ' O,O,:srvn'A*r

- F : 6. oof Yr1
o,o?-L

hn- ""1:r"-
: =: o,u{ nn
$ ,o *}' t*
 T
28. Di Beaty wasin a stateof metabolicacidoses from not takiqgher insulin. Her blood pH wasfound
to be 7.0. Upon arrivalat the hospitalin a comq her breathingwith very deepandrapid. {xpi.ain
(usingapproiriateequilibria)hovrthe rapid breathingacts as a compensatory mechanismfor her
condition.(4pts)
\,
-?- H'(u5 : ?t{o't ilq
c o u= O"&.i Krd

n *j 4
"3"tr-t'1
f oa
[: tr*^kt"+'\'-
'" l 4 4.."! ) t^.L *-?I
( Ptt :,f"
*S ' ^a

29. A Pentapeptide containsAla Met, Phe and_2Ly-s, Tr-eatnentwith trypsin yi"tt a dipeptideand a
with cyanogenbromideyieldsa dipe^p{f anda tripeptide-Edmandegradation
tripeptidb.^Treatment
yietcfuPTH-Alanine.What is the sequenceof the peptide?(Showyow reasoning)(4pts)

A \ ^ - L : , - Y V r ' *P- [ ' - L J t

^() ?l'"t
CF
I+
tar<

? tr [A'
J'P"E
p.rrrurl
t
'l
(t^'* '*-L-

t) /\

Ar.6"PhJ-r
 !r.t {. f"--tg
*__a_ S.& .9,*r'l*,
30. A peptideis 22 aminoacidslong andconsistsentirelyof
@

v (a) Sketcha titrationcurvefor this 22-mer. (2nts)

- a
, " 1 . ((
@
'f 5. 'N - ( ( , ' n
A
, ^
4

s
cqit
o:3
I
, rt'"1*
I e/
A
.t ,
I

e
uL
tn' I %l- Y ) t nL
r'cuNvl
-f^
L ".- ( ^ I B
i,
- e
1 2 ltJJ cc5
'roo:'
S /
,' €- l t r ( \A ) * o t r C-
pL{b
l'ft' ctzt
(b) How manyequlvalentsof NaOH arerequiredto completelytitratethis 22-mer?(lpt)

(c) For thetitrationof 1 functlonalgroup identify the points correspondingto 1007oacid,100Vo

conjugatebase,and thepK.. (2pts)

g.^ a tl"n''

31. Indoleinhibitschymourypsin.

Indole
(a) Whatkind of inhibitor is indole? (lpt)
I I
-tt '-'r
P
L
o*.fi
{ l
< tt
U

(b) Why is indolethis type of inhibitor? (lpt)

\z
,. .{ n

[\nntn"P4te \
 jr,,.,i.

(c) Sketcha Lineweaver-Burkeplot for the type of inhibition. Show a line for no inhibition and a , ,
line for inhibition. Cleariy indicate how the kinetic para:neterschange. (3pt)

u-T-
;U,, Snb
-O+ a^'
V *- * s L".,6, {
V.*t \\>
6;w Lr-*^l
I
. L
32. (a) Whatis theBohreffectf fZpts)
\ **'rfl ., J.' tt/ (,.,L t fl O
tr ) \\ i:r
tll2 pr.Lr _*P

*q (o>k kn6 \s hrr'^'.. d'o6r *{ oL

hr," 1,..Lr

(b) Whatis thestructuralbasisfor the Bohr effect? (2pts)

\-, A 1 >!
q's'itL'*' ol*o* *( g1'\<'( -ttJ-
-f .srr^o. (r s},4,) Y
1a*
t ^ {r
o-Q 90- s h t , . ( * r ^ ' [ h -(\ . o l t t { ' " r h [ r '
*,''-,
f o-^* 1'..h- t J
: ]-L.., sfd'h{-r':{"'^ v'r \^n.
1'^\t^n"t*r Q
n r{ru- s*i *{ /\}& "n'-(
r:
-a{t I h
L+r co1
'{o'''^s € ( n^'L **{*
I
\ .^- trss,^r. R* vn-
* -t\ O
€) (\ sl* L'l'*-(\
lZ- I-r,,re
-hry
+* €' r\ ''" F }' I co^L ^J'*
I ,^ R_ {r'-'-*
* Q"^J J
{,aU
"I have neither participatedin nor witnessedany acts of academicdishonestypertaining
to this
examinationor assignment." (signature)
\t