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%& 'iscuss the #ole o( )hos)hoglucomutase in
glycogenesis&
$ns& *lycogenesis #e(e#s to synthesis o( glycogen&
*lucose % )hos)hate+ the end )#oduct o( glycogen
)hos)ho#ylase #eaction is con,e#ted to glucose -
)hos)hates by )hos)hoglucomutase enzyme+ .hich
catalyses #e,e#sible #eaction& /nitially
)hos)ho#ylated at a Se# #esidue+ the enzyme
donates a )hos)ho#yl g#ou) to 01- o( the subst#ate+
and then acce)ts a )hos)ho#yl g#ou) (#om 01%&
2& 3i,e# and muscle ha,e glucose1-1)hos)hatase
acti,ity& 4#ue o# (alse5
$ns& 3i,e# has glucose1-1)hos)hatase acti,ity .he#eas
muscle lac6 glucose1 -1 )hos)hatase acti,ity&
4he glucose -1)hos)hate (o#med (#om glycogen in
s6eletal muscle can ente# glycolysis and se#,e as an
ene#gy sou#ce to su))o#t muscle cont#action& /n
li,e#+ glycogen b#ea6do.n se#,es a di7e#ent
)u#)ose to #elease glucose into the blood .hen the
blood glucose le,el d#o)s+ as it does bet.een meals&
4his #e8ui#es an enzyme+ glucose -1)hos)hatase+
that is )#esent in li,e# and 6idney but not in othe#
tissues& 4he enzyme is an integ#al memb#ane
)#otein o( the endo)lasmic #eticulum+ )#edicted to
contain nine t#ans1memb#ane helices+ .ith its acti,e
site on the lumenal side o( the ER& *lucose -1
)hos)hate (o#med in the cytosol is t#ans)o#ted into
the ER lumen by a s)eci9c t#ans)o#te# (4%) and
hyd#olyzed at the lumenal su#(ace by the glucose -1
)hos)hatase& 4he #esulting "i and glucose a#e
thought to be ca##ied bac6 into the cytosol by t.o
di7e#ent t#ans)o#te#s (42 and 4!)+ and the glucose
lea,es the he)atocyte ,ia yet anothe# t#ans)o#te# in
the )lasma memb#ane (*3:42)& by ha,ing the
acti,e site o( glucose -1)hos)hatase inside the ER
lumen+ the cell se)a#ates this #eaction (#om the
)#ocess o( glycolysis+ .hich ta6es )lace in the
cytosol and .ould be abo#ted by the action o(
glucose -1)hos)hatase& *enetic de(ects in eithe#
glucose -1)hos)hatase o# 4% lead to se#ious
de#angement o( glycogen metabolism+ #esulting in
ty)e /a glycogen sto#age disease
Because muscle and adi)ose tissue lac6 glucose -1
)hos)hatase+ they cannot con,e#t the glucose -1
)hos)hate (o#med by glycogen b#ea6do.n to
glucose+ and these tissues the#e(o#e do not
cont#ibute glucose to the blood&
!& 'iscuss the e7ect o( glucagon on acti,ities o(
glycogen synthase and glycogen )hos)ho#ylase
$ns& 4he s)ecial #ole o( li,e# in maintaining a constant
blood glucose le,el #e8ui#es additional #egulato#y
mechanisms to coo#dinate glucose )#oduction and
consum)tion& When the blood glucose le,el
dec#eases+ the ho#mone glucagon signals the li,e# to
)#oduce and #elease mo#e glucose and to sto)
consuming it (o# its o.n needs& One sou#ce o(
glucose is glycogen sto#ed in the li,e#; anothe#
sou#ce is gluconeogenesis&
Bet.een meals+ o# du#ing an extended (ast+ the d#o)
in blood glucose t#igge#s the #elease o( glucagon+
.hich acti,ates "K$& "K$ mediates all the e7ects o(
glucagon& /t )hos)ho#ylates )hos)ho#ylase 6inase+
acti,ating it and leading to the acti,ation o(
glycogen )hos)ho#ylase& /t )hos)ho#ylates glycogen
synthase+ inacti,ating it and bloc6ing glycogen
synthesis& /t )hos)ho#ylates "<K12=<B"ase12+ leading
to a d#o) in the concent#ation o( the #egulato#
(#uctose 2+-1bis)hos)hate+ .hich has the e7ect o(
inacti,ating the glycolytic enzyme "<K1% and
acti,ating the gluconeogenic enzyme <B"ase1 $nd it
)hos)ho#ylates and inacti,ates the glycolytic
enzyme )y#u,ate 6inase& :nde# these conditions+
the li,e# )#oduces glucose -1)hos)hate by glycogen
b#ea6do.n and by gluconeogenesis and it sto)s
using glucose to (uel glycolysis o# ma6e glycogen+
maximizing the amount o( glucose it can #elease to
the blood& 4his #elease o( glucose is )ossible only in
li,e#+ because othe# tissues lac6 glucose -1
)hos)hatase
Part B
%& What is the signi9cance o( chemiosmotic theo#y5
4he chemiosmotic model+ .as )#o)osed by "ete#
Mitchell+ $cco#ding to the model the
elect#ochemical ene#gy inhe#ent in the di7e#ence in
)#oton concent#ation and se)a#ation o( cha#ge
ac#oss the inne# mitochond#ial memb#ane (the
)#oton1moti,e (o#ce) d#i,es the synthesis o( $4" as
)#otons >o. )assi,ely bac6 into the mat#ix th#ough
a )#oton )o#e associated .ith $4" synthase&
Mitchell used ?chemiosmotic@ to desc#ibe enzymatic
#eactions that in,ol,e+ simultaneously+ a chemical
#eaction and a t#ans)o#t )#ocess 0hemiosmotic
theo#y #eadily ex)lains the de)endence o( elect#on
t#ans(e# on $4" synthesis in mitochond#ia&
When the >o. o( )#otons into the mat#ix th#ough the
)#oton channel o( $4" synthase is bloc6ed (.ith
oligomycin+ (o# exam)le)+ no )ath exists (o# the
#etu#n o( )#otons to the mat#ix+ and the continued
ext#usion o( )#otons d#i,en by the acti,ity o( the
#es)i#ato#y chain gene#ates a la#ge )#oton g#adient&
4he )#oton1moti,e (o#ce builds u) until the cost
((#ee ene#gy) o( )um)ing )#otons out o( the mat#ix
against this g#adient e8uals o# exceeds the ene#gy
#eleased by the t#ans(e# o( elect#ons (#om A$'H to
O2(oxygen)& $t this )oint elect#on >o. must sto);
the (#ee ene#gy (o# the o,e#all )#ocess o( elect#on
>o. cou)led to )#oton )um)ing becomes ze#o+ and
the system is at e8uilib#ium&
2& *lycogenesis is the #e,e#sal o( glycogenolysis& 4#ue o#
(alse 5 Why5
$ns& <alse that is+ glycogenesis is not #e,e#sal o(
glycogenolysis&
*lycogenesis in,ol,e synthesis o( glycogen .he#e as
glycogenolysis #e(e#s to b#ea6 do.n o( glycogen to
glucose - )hos)hate&
$lthough the t.o )#ocesses seem to be #e,e#sal o( each
othe#+ they a#e di7e#ent )#ocesses&
*lycogenolysis in,ol,e (o#mation o( glucose1-1
)hos)hate (#om glycogen .ith hel) o( th#ee
enzymes; glycogen )hos)ho#ylase+ glycogen de
b#anching enzyme and )hos)ho gluctamase&
*lycogen )hos)ho#ylase catalyzes the #eaction in
.hich an (al)ha%1B) glycosidic lin6age bet.een t.o
glucose #esidues at a non #educing end o( glycogen
unde#goes attac6 by ino#ganic )hos)hate ("i)+
#emo,ing the te#minal glucose #esidue as '1glucose
%1)hos)hate (*lucose %1)hos)hate+ the end )#oduct
o( the glycogen )hos)ho#ylase #eaction+ is
con,e#ted to glucose -1)hos)hate by
)hos)hoglucomutase+ .hich catalyzes the #e,e#sible
#eaction
Whe#eas glycogenesis in,ol,es (o#mation o( glycogen
.ith hel) o( t he Suga# Aucleotide :'"1*lucose
.hich 'onates *lucose (o# *lycogen Synthesis& :'"1
glucose is the immediate dono# o( glucose #esidues
in the #eaction catalyzed by glycogen synthase+
.hich )#omotes the t#ans(e# o( the glucose #esidue
(#om :'"1glucose to a non #educing end o( a
b#anched glycogen molecule& 4he o,e#all e8uilib#ium
o( the )ath (#om glucose -1)hos)hate to lengthened
glycogen g#eatly (a,ou#s synthesis o( glycogen&
*lycogen synthase cannot ma6e the (al)ha %1-)
bonds (ound at the b#anch )oints o( glycogen; these
a#e (o#med by the glycogen1b#anching enzyme+ also
called amylo (%nB) to (%n-) t#ansglycosylase o#
glycosyl1 (Bn-)1t#ans(e#ase& 4he glycogen1b#anching
enzyme catalyzes t#ans(e# o( a te#minal (#agment o(
- o# C glucose #esidues (#om the non #educing end o(
a glycogen b#anch ha,ing at least %% #esidues to the
01- hyd#oxyl g#ou) o( a glucose #esidue at a mo#e
inte#io# )osition o( the same o# anothe# glycogen
chain+ thus c#eating a ne. b#anch& <u#the# glucose
#esidues may be added to the ne. b#anch by
glycogen synthase&
!& What is di7e#ence in subst#ate and oxidati,e
)hos)hoylation5
Subst#ate le,el )hos)ho#ylation includes (o#mation o(
$4" (adenosine t#i )hos)hate by the di#ect t#ans(e#
and donation o( )hos)ho#yl g#ou) to adenosine di
)hos)hate (#om )hos)ho#ylated #eaction
inte#mediate& <o# exam)le the )hos)ho#yl t#ans(e#
(#om %+ ! bi)hos)ho glyce#ate to $'" is an exam)le
o( subst#ate le,el )hos)ho#ylation
Oxidati,e )hos)ho#ylation is a metabolic )ath.ay that
uses ene#gy #eleased by the oxidation o( nut#ients
to )#oduce adenosine t#i)hos)hate ($4")& 'u#ing
oxidati,e )hos)ho#ylation+ elect#ons a#e t#ans(e##ed
(#om elect#on dono#s to elect#on acce)to#s such as
oxygen+ in #edox #eactions& 4hese #edox #eactions
#elease ene#gy+ .hich is used to (o#m $4"& /n
eu6a#yotes+ these #edox #eactions a#e ca##ied out by
a se#ies o( )#otein com)lexes .ithin mitochond#ia+
.he#eas+ in )#o6a#yotes+ these )#oteins a#e located
in the cellsD inne# memb#anes& 4hese lin6ed sets o(
)#oteins a#e called elect#on t#ans)o#t chains
'ate Sig& o( <aculty membe#
Rema#6s by HO'
(Mandato#y)
Sig& o( HO' .ith date
Rema#6s by HOS (Mandato#y)
Sig& o( HOS .ith date