BIOC13H3 Lecture Notes - Lecture 15: Cytosol, Glycerol, Mitochondrion

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BIOC13:(Lecture(17( ( Final(
March(15,(2018(
55"
Electron)Transport)Network!
Fate%of%NADH%
NADH’s"oxidation"is"highly"exergonic"due"to"its"low"reduction"potential"
Assuming"100%"efficiency,"1"NADH"can"produce"up"to"7"ATP"
o By"the"end"of"Krebs,"there"are"10"NADH"to"be"oxidized"per"glucose"
§ 70"ATP"
At"more"realistic"50%"efficiency,"35"ATP"would"be"made"from"10"NADH"
molecules"
Throughout"the"ETN,"electrons"are"passed"to"carriers"(with"oxygen"as"final"
acceptor)"to"physically"link"system"and"conserve"all"the"energy"
Energy"is"released"in"small"pieces"to"improve"efficiency"
Inner%Mitochondrial%Membrane%
The"inner"mitochondrial"membrane"is"completely"impermeable"to"NAD+"and"
NADH"
o No"transport"proteins"to"get"them"in"
NADH"produced"in"Krebs"cycle"is"already"in"matrix"and"doesn’t"need"to"pass"
through"the"IMM"à"complex"already"there"to"oxidize"it"
NADH"from"glycolysis"is"in"the"cytosol"and"needs"to"be"transported"to"the"ETN"
complexes"
Why$Keep$It$Impermeable$to$NADH?$
Researchers"created"an"IMM"that"is"permeable"to"NADH"in"attempt"to"figure"
out"why"not"make"it"permeable"to"NADH/NAD+"
Adding"a"transporter"caused"drastic"increase"in"presence"of"NADH/NAD+"in"the"
matrix"and"very"few"left"in"the"cytosol"for"glycolysis"
It"is"therefore"concluded"that"the"IMM"is"impermeable"to"NADH"so"that"it"
doesn’t"steal"the"cytosol’s"pool"of"NADH"
%NADH%Shunt%
There"are"2"shuttles"for"bringing"
electrons"from"NADH"in"the"
cytosol"to"the"ETN"
Glycerol-3-Phosphate$Shuttle$$
NADH"is"oxidized"by"Gly3PDH"and"
electrons"are"passed"to"DHAP,"
creating"Gly3P"
Gly3P"goes"to"the"mitochondria"
where"another"Gly3PDH"passes"
the"electrons"to"FAD,"creating"
FADH2"
o The"Gly3P"is"now"DHAP"
once"again"and"can"repeat"
the"process"
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BIOC13:(Lecture(17( ( Final(
March(15,(2018(
56"
FADH2"passes"the"electrons"to"ubiquinone"(the"first"electron"carrier)"
Free"energy"is"released"but"it"isn’t"conserved"à"shuttle"is"inefficient"
Malate-Aspartate$Shuttle$$
This"shuttle"system"is"only"favourable"when"NADH/NAD+"is"greater"in"cytosol"
than"matrix"(this"rarely"occurs)"
Malate(dehydrogenase"(MDH)"oxidizes"NADH"and"the"electrons"are"passed"to"
OAA,"forming"malate"
The"malate"is"transported"across"
the"IMM"and"into"the"matrix,"
using"a"proton"from"the"gradient"
to"do"so"
MDH"oxidizes"malate"back"into"
OAA"with"the"electron"being"
accepted"by"matrix"NAD"to"get"
NADH"in"the"matrix"
Getting"the"OAA"back"into"cytosol"is"
complicated"
OAA"goes"through"
transamination(reaction"with"glutamate"to"create"aspartate"
o The"glutamate"is"thus"converted"to"α-ketoglutarate"
Aspartate"is"then"transported"into"the"cytosol"by"an"H+/Aspartate"anti-porter"
(thus"using"proton"gradient"again)"
Asparatate"then"reacts"with"α-ketoglutarate"(that"was"transported"from"matrix"
to"the"cytosol)"to"get"OAA"again"
o Glutamate"is"created"and"can"be"reused"
This"OAA"can"be"used"again"
Note:"Both"the"glutamate"and"OAA"are"thus"recycled,"conserving"energy"
Which$Shuttle$Being$Used?$
The"type"of"shuttle"used"depends"on"
the"efficiency"of"metabolism"
Researchers"had"participants"
complete"8"months"of"endurance"
training"and"measured"shuttle"
activity"before"and"after"the"training"
Malate"shuttle"usage"increased"after"
the"8"months"endurance"while"the"
Gly3P"shuttle"usage"decreased"
Since"it"is"more"efficient,"malate"
shuttle"increases"endurance"it"seems"
which"makes"sense"
In"the"cold,"Gly3P"is"favourable"as"you"have"more"heat"to"stay"warm"
Mammalian%Mitochondria%
The"ETN"is"mammals"is"relatively"simple"and"well"studied"
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Document Summary

Inner mitochondrial membrane: the inner mitochondrial membrane is completely impermeable to nad+ and. It is therefore concluded that the imm is impermeable to nadh so that it doesn"t steal the cytosol"s pool of nadh. Nadh shunt: there are 2 shuttles for bringing electrons from nadh in the cytosol to the etn. Glycerol-3-phosphate shuttle: nadh is oxidized by gly3pdh and electrons are passed to dhap, creating gly3p, gly3p goes to the mitochondria where another gly3pdh passes the electrons to fad, creating. Fadh2: the gly3p is now dhap once again and can repeat the process. Final: fadh2 passes the electrons to ubiquinone (the first electron carrier, free energy is released but it isn"t conserved shuttle is inefficient. Malate-aspartate shuttle: this shuttle system is only favourable when nadh/nad+ is greater in cytosol than matrix (this rarely occurs, malate dehydrogenase (mdh) oxidizes nadh and the electrons are passed to.

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