1. (2)ATP합성
ATP합성효소의 전자현미경사진 및 모식도(그림 )
작은 미토콘드리아입자(SMP), 초음파분해, 안에서밖으로 돌출
F1, F0단위
(3)산화적 인산화의 제어
-P/O비율(각각의 산소원자가 물분자로 환원되는데 소모되는 Pi몰의 수
-ADP에 의한 호기성 호흡의 제어를 호흡통제라함
-ATP-ADP전위체(translocator)와 인산운반체(phosphate carrier)같은 수송단백질이 미토콘드리아 내 ADP, ATP의 농도를 조절(그림10.16)

2. Section 10.2: Oxidative Phosphorylation
ATP Synthesis Continued
F1 unit has five subunits: a3, b3, g, d, and e
F0 unit has three subunits: a, b2, and c12
F0 motor converts the proton motive force into the rotational force of the central shaft (e and g subunits) that, in turn, drives ATP synthesis
Figure The ATP Synthase From Escherichia coli
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

3. Section 10.2: Oxidative Phosphorylation
ATP Synthesis Continued
b subunits of the ATP synthase have three conformations: open (O), tight (T), and loose (L)
Steps:
1. ADP and Pi bind to L site; rotation converts it to T conformation
2. ATP synthesized
3. Rotation converts T site to O site, releasing ATP
Figure ATP Synthesis Model
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

4. Section 10.2: Oxidative Phosphorylation
Control of Oxidative Phosphorylation
Activated when ADP (respiratory control) and Pi concentrations are high
Inhibited when ATP concentrations are high
Figure The ADP-ATP Translocator and the Phosphate Translocase
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

5. Section 10.2: Oxidative Phosphorylation
Control of Oxidative Phosphorylation Cont.
Amounts of ATP and ADP in mitochondria are controlled by the ADP-ATP translocator
Amount of H2PO4- is controlled by phosphate carrier (H2PO4-/H+ symporter)
Figure The ADP-ATP Translocator and the Phosphate Translocase
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

6. (4)글루코오스의 완전산화
-ATP생성원(표10.2)
-NADH는 미토콘드리아내막을 통과못함(해당과정 시 생성분의 이동):글리세롤-인산 왕복수송계(그림10.17a)와 말산-아스파르트산 왕복수송계(그림10.17b)을 발전
(5)짝풀린 전자수송(탈공역 전자수송과 열생산)
-신생아, 동면동물 및 추운지역에 사는 동물은 대사에 의해 열생산
-갈색, 많은 미토콘드리아로
-갈색지방세포의 미토콘드리아 내막속의 단백질 중 10%는 탈공역단백질(uncoupling protein, UCP)로, 전자수송사슬로 생산된 에너지를 ATP생산하는데 사용치 않고 열생산에 사용

7. Section 10.2: Oxidative Phosphorylation
Figure 10.17a Shuttle Mechanisms That Transfer Electrons from Cytoplasmic NADH to the Respiratory Chain
The Complete Oxidation of Glucose
Two mechanisms to move electrons from cytoplasmic NADH, derived from glycolysis, into the mitochondrial ETC are glycerol phosphate shuttle and malate-aspartate shuttle
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

8. Section 10.2: Oxidative Phosphorylation
Figure 10.17a Shuttle Mechanisms That Transfer Electrons from Cytoplasmic NADH to the Respiratory Chain
The Complete Oxidation of Glucose Continued
The glycerol phosphate shuttle uses cytoplasmic NADH (glycolytic pathway) to reduce DHAP into glycerol-3-phosphate, which can enter the intermembrane space
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

9. Section 10.2: Oxidative Phosphorylation
The Complete Oxidation of Glucose Continued
The malate-aspartate shuttle is used to transfer electrons from cytoplasmic NADH (glycolytic pathway) to the mitochondrial ETC
This is the more efficient of the two mechanisms
Figure 10.17b Shuttle Mechanisms That Transfer Electrons from Cytoplasmic NADH to the Respiratory Chain
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

10. Section 10.2: Oxidative Phosphorylation
The Complete Oxidation of Glucose Continued
Cytoplasmic NADH reduces oxaloacetate to malate, which is transported to the matrix
Malate is reoxidized to produce NADH
Figure Shuttle Mechanisms That Transfer Electrons from Cytoplasmic NADH to the Respiratory Chain
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

11. Section 10.2: Oxidative Phosphorylation
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

12. 10.3 산소, 세포기능 및 산화적 스트레스
-반응성 산소종(reactive oxygen species, ROS)
-항산화제(antioxidant)
-산화적스트레스
-산소를 소모하는 반응과정인 호흡파열(respiratory burst)시 ROS생성, 세포파괴
(1)반응성 산소종
-라디컬: 하나 혹은 그 이상의 쌍을 이루지 않는 전자를 포함한 원자
-전자가 전자수송회로를 새어나와 산소와 결합하여 ROS형성, 초과산화물라디칼은 대부분 복합체III의 Q회로 및 플라보단백질 복합체I에서 생산(그림10.18)
2H+ + 2O2- → O2 + H2O2
Fe2+ + H2O2 → Fe3+ + •OH + OH-
-히드록시 라디칼(•OH )은 자가촉매 라디칼 연쇄반응을 하여 위험(그림10.19): 지질의 과산화반응은 라디칼절단반응으로
-단일항 산소(1O2):
2O2- + 2H+ → H2O2 + 1O2
2ROOH → 2ROH + 1O2
-ROS는 생체이물(xenobiotic)대사나 백혈구의 호흡파열로도 형성(그림10.20)
;1)세균의 파고솜내 이입, 리소좀과결합, 초과산화물 라디칼형성, SOD에 의해 H2O2형성, 미엘로과산화효소에 의해 살균물질인 하이포할로겐 화합물형성. 2) Fe존재 하에 •OH 와 1O2형성

13. All living processes take place within a redox environment
Section 10.3: Oxygen , Cell Function, and Oxidative Stress
All living processes take place within a redox environment
Redox state is regulated within a narrow range because of redox-sensitive nature of many pathways
Important linked redox pairs (NAD(P)H/NAD(P)+ and GSH/GSSG) help maintain redox conditions
GSH (glutathione) is a key cellular-reducing agent
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

14. Antioxidants interact with ROS to mitigate damage
Section 10.3: Oxygen , Cell Function, and Oxidative Stress
Oxygen usage comes with the danger of forming reactive oxygen species (ROS)
Some ROS act as signaling molecules
Antioxidants interact with ROS to mitigate damage
Under certain conditions, antioxidant mechanisms are overwhelmed, leading to oxidative stress
Oxidative damage has been linked to 100 human diseases
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

15. Reactive Oxygen Species
Section 10.3: Oxygen , Cell Function, and Oxidative Stress
Figure Overview of Oxidative Phosphorylation and ROS Formation in the Mitochondrion
Reactive Oxygen Species
Properties of oxygen related to its structure
Diatomic oxygen is a diradical, meaning it has two unpaired electrons
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

16. Reactive Oxygen Species Continued
Section 10.3: Oxygen , Cell Function, and Oxidative Stress
Figure Overview of Oxidative Phosphorylation and ROS Formation in the Mitochondrion
Reactive Oxygen Species Continued
Oxygen can only accept one electron at a time
Electrons can leak out of the ETC and interact with O2
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

17. Types of reactive oxygen species:
Section 10.3: Oxygen , Cell Function, and Oxidative Stress
Types of reactive oxygen species:
First created is superoxide radical (O2●-), which acts as a nucleophile
O2●- can react with itself to form hydrogen peroxide H2O2
H2O2 can react with Fe2+ to form hydroxyl radical (●OH), which can initiate autocatalytic radical chain reaction
Figure Radical Chain Reaction
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

18. Section 10.3: Oxygen , Cell Function, and Oxidative Stress
Singlet oxygen (1O2) formed from H2O2 or superoxide can be damaging to aromatics and conjugated alkenes
Figure Radical Chain Reaction
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

19. There are also reactive nitrogen species (RNS)
Section 10.3: Oxygen , Cell Function, and Oxidative Stress
There are also reactive nitrogen species (RNS)
Nitric oxide, nitrogen dioxide, and peroxynitrite are important examples
Nitric oxide (●NO) is an important signaling molecule
Physiological functions of NO include blood pressure regulation, inhibition of blood clotting, and destruction of foreign cells by macrophages
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

20. Section 10.3: Oxygen , Cell Function, and Oxidative Stress
Figure The Respiratory Burst
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

21. Reactive oxygen species also generated for the respiratory burst
Section 10.3: Oxygen , Cell Function, and Oxidative Stress
Reactive oxygen species also generated for the respiratory burst
Macrophages and neutrophils actively make large quantities of ROS
Use ROS in order to destroy microorganisms and damaged cells
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

22. (2)항산화제의 효소계
-초과산화물 불균형효소(SOD): 초과산화물 라디칼에서 H2O2와 O2형성을 촉매, Cu-Zn 동위효소, Mn을 함유한 동위효소.
-카탈라아제(catalase):헴함유 효소로 H2O2를 환원
-글루타티온 과산화효소(glutathione peroxidase): Se을 함유하며 GSH를 이용하여 다양한 물질을 환원, H2O2의 환원 및 유기과산화물을 알코올로 전환
-글루타티온 과산화효소를 보조하는 여러 효소(그림10.21), 이 반응의 NADPH는 오탄당인산회로에 의해 공급
-티오레독신 중심계(그림10.22)
(3) 항산화제분자
-라디칼 등 ROS를 제거함
-GSH, α-토코페롤(비라민E, 페놀 항산화제), 아스코르브산(비타민C), β-카로틴[레티놀(비타민A)의 전구물질] 등(그림10.23)
-아스코르브산에 의한 α-토코페롤의 재생(그림10.24)
* 심근경색: 심허열 및 재주입

23. Antioxidant Enzyme Systems
Section 10.3: Oxygen , Cell Function, and Oxidative Stress
Antioxidant Enzyme Systems
To protect against oxidative stress, living organisms have developed several antioxidant defense mechanisms
Major enzymatic defenses are provided by four enzymes: superoxide dismutase, glutathione peroxidase, peroxiredoxin, and catalase
Superoxide dismutase forms H2O2 and O2 from superoxide radical
Catalase forms H2O and O2 from H2O2
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

24. Antioxidant Enzyme Systems Continued
Section 10.3: Oxygen , Cell Function, and Oxidative Stress
Figure The Glutathione-Centered System
Antioxidant Enzyme Systems Continued
Glutathione peroxidase uses the reducing agent GSH to control peroxide levels
Reduces H2O2 to form water and transforms organic peroxides to alcohols
Glutathione reductase is also an important enzyme in the glutathione system
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

25. Antioxidant Enzyme Systems Continued
Section 10.3: Oxygen , Cell Function, and Oxidative Stress
Figure The Thioredoxin-Centered System
Antioxidant Enzyme Systems Continued
Peroxiredoxins (PRX) are a class of enzymes that detoxify peroxides
Uses thiol-containing peptides like thioredoxin
Thioredoxin is involved in redox reactions mediated by the peroxiredoxin/thioreductase system
From McKee and McKee, Biochemistry, 5th Edition, © 2011 Oxford University Press

26. Antioxidant Molecules
Section 10.3: Oxygen , Cell Function, and Oxidative Stress
Figure Selected Antioxidant Molecules
Antioxidant Molecules
Organisms use antioxidant molecules to protect themselves from radicals
a-Tocopherol (vitamin E) is a potent, lipid-soluble radical scavenger
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

27. Antioxidant Molecules Continued
Section 10.3: Oxygen , Cell Function, and Oxidative Stress
Figure Selected Antioxidant Molecules
Antioxidant Molecules Continued
b-carotene, a carotenoid, is a precursor of vitamin A (retinol): a potent, lipid-soluble radical scavenger in membranes
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press

28. Antioxidant Molecules Continued
Section 10.3: Oxygen , Cell Function, and Oxidative Stress
Figure Regeneration of a-Tocopherol by L-Ascorbate
Antioxidant Molecules Continued
Ascorbate protects membranes through two mechanisms: scavenging a variety of ROS in aqueous environments and enhancing the activity of a-tocopherol
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press