BIOC13H3 Lecture Notes - Lecture 9: Citric Acid Cycle, Voltage-Dependent Anion Channel, Intermembrane Space
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4*5(%67(38%9(
34#
Citric%Acid%Cycle!
• The#+0,.0+(:+01(+;+<*#($=$)#is#the#final,#
common#pathway#for#catabolism#of#a#bunch#
of#molecules#
• Therefore,#deficiencies#in#citric#acid#cycle#can#
result#in#death#of#the#organism#
• Anabolic#role#in#building#many#molecules#
• An#:2>?05@<0+(>:,?A:;#meaning#that#it#is#
involved#in#both#catabolism#and#anabolism#
Structure'of'Mitochondria'
• The#citric#acid#cycle#occurs#in#the#
mitochondria#
• The#mitochondria#has#an#outer#and#inner#membrane#with#the#inner#membrane#
being#folded#
o The#folds#increase#surface#
area#of#the#IM#which#is#good#
because#that’s#where#the#
proteins#of#the#*<*+,.@B(
,.:BC>@.,(+?:0B#are#
o Allows#for#maximized#ATP#
production#capacity#
• "B,*.2*25.:B*(C>:+*#is#the#space#
between#the#two#membranes#
• The#20,@[email protected]:<(2:,.0D#is#the#
space#inside#the#inner#membrane#
o Where#the#enzymes#of#the#citric#acid#cycle#are#found#
o Also#have#circular#DNA#(likely#from#bacteria#mitoncdria#believed#to#
have#evolved#from)#
• The#@-,*.(2*25.:B*#is#highly#permeable#to#metabolites#but#not#protein#
(since#they#are#too#large)#
• Proteins#are#transported#into#the#mitochondria#via#>@.0BC#
o Not#very#selective#
o EF=$#is#the#voltage#dependent#porin#that#controls#protein#entry#into#
the#mitochondria#
Voltage'Dependent'Anion'Channel'
• EF=$#is#structured#like#a#barrel#
• When#there#is#no#voltage,#VDAC#is#
open#and#things#can#move#through#it#
• When#positively#charged,#the#red#
protein#on#the#barrel#changes#shape#so#
that#barrel#closes#
#
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35#
• The#ETC#pumps#protons#from#matrix#into#the#intermembrane#space#(IMS),#
making#the#IMS#positively#charged#
• This#causes#the#VDAC#to#close#so#that#none#of#the#
protons#leak#out#of#the#membrane,#ruining#the#
proton#gradient#that#is#trying#to#be#established#
• Reopen#when#the#proton#gradient#is#gone#
Inner'Membrane'Transports'
• The#IM#is#permeable#to#most#things#
• There#are#very#specific#transporters#for#everything#
that#needs#to#get#across#
• There#are#transporters#for#moving#ATP,#making#
pyruvate,#moving#phosphate#
• Need#energy#for#most#of#these#things#to#get#across,#generally#provided#by#the#
proton#gradient#
Elucidation??'à'See'if'he'has'any'questions'on'this'
Citric'Acid'Cycle'
Pre-Citric'Acid'Cycle'Conversion'Pyruvate'to'Acetyl-CoA'
• Before#citric#cycle#begins,#pyruvate#is#converted#into#:+*,;<G$@=(H=$@=I#
• First,#mitochondria#needs#to#be#transported#into#the#mitochondria#
VDAC#channel#lets#it#through#easily#
• The#inner#membrane#uses#>;.-J:,*(,.:BC<@+:C*#to#transport#pyruvate#into#
the#mitochondrial#matrix#
o Co-transports#H+#into#the#cell#as#well#to#power#this#
• KFL#(pyruvate#dehydrogenase)(+@2><*D#is#in#the#mitochondria#
o A#bunch#of#enzymes#joined#to#create#one#structure#
o Decarboxylizes#the#pyruvate,#oxidizes#it#and#then#sticks#a#CoA#on#it#to#
make#ACoA#
Pyruvate)Translocase)
• Also#called#/0,@[email protected]:<(>;.-J:,*(
+:..0*.(H/K$I,#>;.-J:,*(,.:BC<@+:C*#
is#made#of#2#proteins#(MPC1#and#
MPC2)#to#join#to#make#a#dimer#
• This#enzyme#is#not#functional#without#
the#dimer#
• Reducing#the#pH#results#in#even#
greater#pyruvate#transport#à#proof#
that#need#H+#gradient#
• Cancer#cells#don’t#express#both#MPC1#
and#MPC2#
o They#prefer#lactate#fermentation#and#therefore#don’t#want#pyruvate#to#
get#into#the#mitochondria#à#non-functional#pyruvate#translocase#