Principle of Bioenergetics and Biological Oxidation

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????

• ???????????

Principle of Bioenergetics and Biological
Oxidation
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????(biological oxidation)???
????????????????,????????????????????????,????CO2
? H2O?????????????CO2,????????,???????(cellular
respiration)?
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?????????
O2
CO2?H2O
ADPPi
??
ATP
??
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???????????

• ??????? ------- ???
• ? ?????
• ??CoA
• ?
• TCA ??????
• ? ? (?????)
• H2OATP CO2

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?????

• ????
• ??
  ????
• ????
• 
  
• ???? ????
• ?????

?? ??
?? ??
??
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????????????

• 1. ????,37?
• ??
• 2. ??????,????,????,???
• ??????????,??????
• 3. ????????,4055
• ????,0
• 4. CO2??????????
• ??????

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??

• ???????? CO2H2O
• ??????,??ATP
  ????,?????
• ?????????????

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• ???
• ?????????
• Principles of Bioenergetics

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?????????????
(?)?????????????

• ??????????????????? ?
• ??????????,???????????????
• ?????????????????????????????????????????

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(?)??????? ???????????

• ?(entropy)???????????????
• ???G(??????)??????????????????

?Glt0,????? ?Ggt0,???????( ?G???,???
???,??????????) ?G0,??????????
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• ?Gº ???????1 mol/L,?????25?,???1????,??Gº????????
  ??
• ?Gº????????,?pH??7.0,???????????????Gº????

?Gº????????Keg????
?Gº? -2.303 RT log Keg
R?????R8.3110-3kJ/molK,T??????
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?????????????????

• (?)???????????????????????

A C ? B D ??
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• (?)???????????????????????

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• (?)????????????????????????

A
D
E

C
B
E
E???????,E?????????
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??ATP??????????????????????
(?)??????????????????????
???????

• ????Gº???ATP(??ATP),??Gº???21 kJ/mol??????????????
  ??
• ???P????????

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??????????????????????????
??? ?Gº? ?Gº?
??? kJ/mol (kcal/mol)
???????? -61.9 (-14.8)
?????? -51.4 (-12.3)
1, 3-?????? -49.3 (-11.8)
???? -43.1 (-10.3)
ATP?ADPPi -30.5 (-7.3)
ADP?AMPPi -27.6 (-6.6)
??? -27.6 (-6.6)
1-????? -20.9 (-5.0)
6-???? -15.9 (-3.8)
AMP -14.2 (-3.4)
6-????? -13.8 (-3.3)
3-????? -9.2 (-2.2)
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(?)ATP???????????????????

• ?????????? ??(??)?????????ATP?????????????,???
  ????????

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• (?)?????(adenylate kinase)??????????????
• ATPAMP 2ADP

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• (?)?????????UTP?CTP?GTP??

ATPUDP?ADPUTP ATPCDP?ADPCTP
ATPGDP?ADPGTP
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• (?)???????????????????

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???ATP??????
ATP
???(????) ???(??????) ???(????) ??(???) ??(????)
ADP
??????????????ATP????
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??? ?????Oxidative Phosphorylation

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??????????????

• ??
• ???????????(2H)????????????????????,?????????,????
  ?????????(respiratory chain)???????(electron
  transfer chain)?
• ??
• ?????????(2H ? 2H 2e)

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(?)??????4???????
??????????
?? ? Cyt c ??????????????
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?????????????????
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1. ?????NADHH???????????(ubiquinone)
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NAD?NADP???
RH NAD RH2PO3NADP
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NAD(NADP) ????????
??????????????????????
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FMN????????
FMN???????,?????????,???????????????FMN ?
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???(iron-sulfur cluster )???
??????????(Fe-S)???????????,????????Fe2 ? Fe3e
???????
? ?????
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???? (iron-sulfur protein )
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??????????
??(Coenzyme Q , CoQ, Q)??????????????????(?CoQ10),
????????????????????
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?????????????????

• NADH ? FMN ? N1a ?(N3, N1b, N4)? N2 ? QP-N
  ? Q

(Fe2S2) (Fe4S4) (Fe2S2) (Fe4S4)(Fe4S4)
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2.????????????????
???????????
????FAD???????????????????
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? ? ? ?(Cytochrome,Cyt)
???????????(heme)??????????,??????????????
????????????????
???? ??(nm) ??(nm) ??(nm)
???? a ß ?
a 600 439
b 562 532 429
c 550 521 415
c1 554 524 418
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3. ?????????????????c
??-????C ?????????
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?????????????Q??(Q cycle)???
QH2
QH2
QH2
QH2
QH2
2H
2H
Q
Q
e
e
e
e
e
Fe2S2
bL
e
Fe2S2
bL
Q
e
2H
bH
bH
Q
e
e
e
Q
Q
Qi
c1
c1
Q
Q
Q0
Qi
Q0
(2)????QH2????

• (1)????QH2????

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4. ????????????C????
??Cyt a3 ?CuB????????????O2?
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????C???CuA??
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???????a3-CuB??
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HO-Y
O2
HO-Y(Tyrosine 244)
OO
CuB
Fe (?)
Fe (?)
CuB
e -
HO-Y
O-O
CuB
CuB2
Fe (III)
Fe (III)
H, e -
e -
????C???a3-CuB???O2????H2O???
O-Y
HO-Y
OH
O ?
OH CuB
CuB2
Fe (IV)
Fe (III)
H2O
H

HO-Y
HO-Y
OH CuB
O ?
OH
CuB2
Fe (IV)
Fe (III)
H
e -
HO-Y
H2O
O ?
H
Fe (IV)
? ?
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(?)????????????????????
??????? ? ???????? ?
??????? ? ??????????? ? ?????
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????????????
1. NADH????? NADH ??????Q ??????Cyt c ??????O2 2.
???????? ??? ????? ?Q ??????Cyt c ??????O2
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NADH?????
FADH2?????
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?????
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???????????
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??????

• 1 ??????????????,??
• ?????,????????,??
• ????????
• 2 ??????????????,?
• ???,??,??
• 3 ?????(Mit???)
• ????? I?III?IV
• ??C1,a ????
• ??a3

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??????
3-???????
????A???
???????
??????
a-???????
??????
FAD
Fe-S
FMN
NADH
CoQ Cytb CytC1 CytC Cytaa3 O2

Fe-S
ADP ATP
ADP ATP
ADP ATP
ß-??????
ß-???CoA???
?????
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????????????????ADP???????
?? ????? (oxidative phosphorylation)????????????
???ADP???,??ATP,?????????
??????? (substrate level phosphorylation)
?????????????,?????,?ADP?????ATP????
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(?)??????????????????

• 1. ??P/O?????????????
• P/O ???????,???1mol???(1/2O2)???????(P)?mol?,????
  ??P/O??
• P/O1, (gt0.5) ??1?ATP
• P/Ogt1.5, 2, ?? 2?ATP
• P/Ogt2.5, ?? 3?ATP

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???????????????P/O??

????????,NADH???P/O?????2.5
??????P/O????1.5?
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2.?????????????????????
?Gº'-nF?Eº'
??????????
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(No Transcript)
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?????????

• ?????
• ATP ? ADP Pi
• ATP? P ?G0 30.5KJ/mol
• ?G0 nF ?E0 2?96.5 ?E0
• ??? 30.5, ??E0 0.158
• NADH ?CoQ ?E0 0.36
• CoQ ?Cyt C1 ?E0 0.19 ???ATP
• Cyt aa3 ?O2 ?E0 0.58

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?????????
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(?) ????????????????????????

• ??????(chemiosmotic hypothesis)
• ?????????,????(H)?????????????????,??????????????
  ????,?????????????ADP?Pi??ATP?

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???????????
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??????????????
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(?) ATP?????????????????????ATP
1. ATP??(ATP synthase)?F1 ?F0??
F1????(a3ß3?de??, OSCP, IF1??) F0????(a, b2,
c912??)
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2.????ATP??Fo????????F1?????
??C????,???????????????,?????????????????
c??? d??????,? c???????? ?????
ATP?? Fo?a???c??????
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3.??????ß????????ATP?????
?H??????Fo?a???c???????,???????,3?ß??????????
ATP???????
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ATP?????

• ???
• ???
  ???

ADP Pi
ATP
Pi
ADP
ATP
ATP
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ATP?????

• F1?????????

??
????
??X
??X
????
?
ATP
?
?
?
?
?
?

?
?
H
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????????????????
(?)?????????3?

• ??????????????????
• ? ???(rotenone)
• 2. ?????????????????
• ??????(uncoupling protein, UCP)
• 3. ATP???????????ADP?????????
• ????(oligomycin)

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?????????????
CO?CN-? N3-?H2S
???A ?????



??? ????A ?????
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?????????(?????????)
???
??? ??
?
Q
???
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• ???(oligomycin)
• ??????F0??????,??ATP???

???
ATP???????
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?????????????????
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(?)??????????????ADP??

• ????????ATP??????????????
• ?????(respiratory control ratio, RCR)

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(?)????????????????
???? 1. ??Mit??????,ATP??? 2???????Na,KATP?
????????????? ?ATP?ADPPi? ???ATP???,ATP????
??????,??? ????,??,????
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(?)???DNA????????????

• ???DNA(mitochondrial DNA, mtDNA)?
• ??

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???????? ???????
?µH ????????? Hm?????H Hc ?????H
? ?
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??????????????????
????????????????????,?????????????,????????????
(transporter)?????????
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???????????????????
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(?) ????NADH????????????????

• ?????????
• a-?????? (a-glycerophosphate shuttle)
• ???-?????? (malate-asparate shuttle)

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1. a-?????????????????
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2. ???-????????????????
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(?)???????ATP?ADP????

• ??????(adenine nucleotide translocase)???????(aden
  ine nucleotide carrier)?????????

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(?)Ca2???????????????????
??????Ca2???????????,?????????????(calcium
uniporter)??,?Ca2??????????????Ca2????????????
???Ca2?????Na???Na-Ca2????( Na-Ca2
exchanger)?????
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(?)?????????????3????????
???????????????????????,??????3??100??????????????
,??????,???????????,????????????
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• ???
• ???ATP?????
• Oxidation Without ATP Generation

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?????????P450????????????
????(monoxygenase)
???????????????????(??),??????(hydroxylase)??????
????NADPHH??2H?????,??????????(mixed-function
oxidase)?
??????????P450 (Cyt P450)???
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O2
Fe (?)
e -
CuB
OO
Fe (III)
H2O2
Fe (?)
2H
AH
O-O
Fe (III)
Fe (III)
O2
AOH
H
e -

???????P450??????
O-OH
Fe (III)
Fe (III)
H

H2O
O ?
Fe (IV)
? ?
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? ?
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????????????????

• (?)?????????????????????

????(reactive oxygen species, ROS)
?????(superoxide anion)O2 ????(hydrogen
peroxide)H2O2 ????(hydroxyl free radical)OH
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• ???(free radical)????????????????????
• H2O2?????,?????Fe2?Cu?????????(Fenton)???-??(Hab
  er-Weiss)??????????

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(?)???????????????

• ????????????????????O2?????O2 ,????O2??????
• ????????,FAD????????????2?????O2??H2O2 ,?????OH?
  
• ?????????,????????????????NADPHH,???????FAD?????
  b558??O2??O2????????????

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(?)????????????

• OH?????????????????????????
• OH????????????????,???????????????
• OH???????DNA???????????DNA????
• ??????????????????????????????????

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(?)??????????????
SOD??????? (superoxide dismutase)
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?????????
????????????????????????(glutathione
peroxidase),????H2O2?R-OOH
H2O2 (ROOH)
NADP
2G SH
???????
H2O (ROHH2O)
NADPHH
G S S G