Chapter 4. Biological Oxidation
This presentation is the property of its rightful owner.
Sponsored Links
1 / 95

Chapter 4. Biological Oxidation PowerPoint PPT Presentation


  • 389 Views
  • Uploaded on
  • Presentation posted in: General

Chapter 4. Biological Oxidation. Intredction ATP oxidative phosphorylation Oxidation not producing ATP. introduction  biological oxidation

Download Presentation

Chapter 4. Biological Oxidation

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Chapter 4 biological oxidation

Chapter 4. Biological Oxidation

Intredction

ATP

oxidative phosphorylation

Oxidation not producing ATP


Chapter 4 biological oxidation

introduction

biological oxidation

oxidation run in living body, detailedly, the process which nutrient substance, such as saccharides, lipids, and proteins are oxidized into water and carbon dioxide, and simultaneouslyproduce energy.

Nutrient + O2 H2O + CO2 + energy

ATP + heat


Chapter 4 biological oxidation

  • Characteristics of biological oxidation


Forms of oxidoreduction in biological oxidation

oxidizing reaction

loss of electrons

dehydrogenation

addation of oxygen

reduction reaction

Gain eletrons

Addation of hydrogen

Deoxygenation

+H

+e

[O]

[R]

-e

-H

+O

Forms ofoxidoreductionin biological oxidation


Chapter 4 biological oxidation

glucose

fatty acid + Glycerol

amino acids

General course of biological oxidation

glucogen

triglyceride

protein

AcetylCoA

TAC

ADP+Pi

ATP

CO2

H2O

2H

respiratory chain


Chapter 4 biological oxidation

  • Energy of reaction

G < 0 spontaneous

G = 0equilibrium

G > 0non-spontaneous

G1

G2

G = G2-G1

G0’= - 2.303 R T log Keg = - n F E0’


Section 1 atp

adenosine triphosphoric acid

腺苷三磷酸

Section 1. ATP


Chapter 4 biological oxidation

activation effect


Atp is the main form of energy utilization and store in body and the center of energy conversion

ATP is the main form of energy utilization and store in body and the center of energy conversion.


High energy compound

High-energy compound


Chapter 4 biological oxidation

GDP GTP

ATP + UDP ADP + UTP

CDP CTP

Transformbetween high-energy compounds

nucleoside diphosphate kinase

adenylate kinase

ADP + ADP  ATP + AMP


Chapter 4 biological oxidation

creatine phosphate– store form of ATP in brain and muscle.


Section 2 oxidative phosphorylation

Section 2. oxidative phosphorylation

  • Ways producing ATP:

  • substrate level phosphorylation

  • oxidative phosphorylation

substrate level phosphorylation

--formation of ATP by the way of straight transfer high-energy substrate energy to ADP.


Chapter 4 biological oxidation

1,3-二磷酸甘油酸 + ADP 3-磷酸甘油酸 + ATP

磷酸烯醇式丙酮酸 + ADP 丙酮酸 + ATP

琥珀酰CoA + H3PO4 + GDP 琥珀酸 + CoA-SH +

GTP

+

ADP

ATP

PK


Chapter 4 biological oxidation

I respiratory chain (呼吸链)

aoxidoreduction system which consists of a series of enzyme, coenzyme aligning in mitochondrial inner membrane, function as linksystem transferer of hydrogen and electron.


Chapter 4 biological oxidation

Mitochondria

Respiratory chain


Chapter 4 biological oxidation

Cytc

内外膜间隙侧

Q

I

线粒体内膜

基质侧

electron transfer in respiratory chain

e-

e-

e-

e-

e-

H2O

NADH+H+

延胡素酸

1/2O2+2H+

NAD+

琥珀酸


Chapter 4 biological oxidation

succinic acid oxidation respiratory chain

NADH oxidation respiratory chain


Chapter 4 biological oxidation

Component of respiratory chain

 Co-Q and Cyt C


1 complex nadh q reducase

NADH

FMN,Fe-S

CoQ

(1) complexⅠ— NADH-Q reducase

  • iron-sulphur protein, Flavoprotein with FMN, 42 peptide chains, 850 kD.

  • Bind and oxidize NADH, transfer electrons to Q, release 4H+ to interspace of inner and outer membrane.


Chapter 4 biological oxidation

Structure of NAD+ and NADP+

R=H:NAD+; R=H2PO3:NADP+

NAD+:nicotinamide adenine dinucleotide,CoI

NADP+:nicotinamide adenine dinucleotide phosphate,CoII


Chapter 4 biological oxidation

黄素单核甘酸


Chapter 4 biological oxidation

Fe2+ Fe3+ + e

Fe4S4

ironsulfur protein

Fe-S

Fe2S2, Fe4S4


Chapter 4 biological oxidation

Ubiquinone,Q

(Coenzyme Q,CoQ) 人体中: CoQ10

  • quinones contain a polyisoprene side chain.

  • liposolubility,make it move in mitochondrial inner membrane easily.

  • the only one electron carrier without protein in respiratory chain.


Chapter 4 biological oxidation

2H+

FMN

Fe-S

N-2

Q

QH2

复合体Ⅰ传递电子的过程

2e-

2H+

NAD+

NADH+H+

NADH+H+

FMN

Fe2+

Q

FMNH2

Fe3+

QH2

NAD+

Q

NADH

FMN

Fe-S


Chapter 4 biological oxidation

(2) complexⅡ-

Succinate-CoQ reductase

  • i.e. succinate dehydrogenase, consists at list 4 peptides. Contain one FAD, two ironsulfur protein and one Cyt b560.

  • Transfer electron from succinic acid to Q, do not release H+ to the interspace.

succinic acid→FAD→Fe-S→Q。


Chapter 4 biological oxidation

cytochrome,Cyt 细胞色素

A、structure: colourant protein containing iron porphyrin.

B、typing: Cyta: Cytaa3

Cytb: Cytb562、Cytb566、 Cytb560

Cytc: Cytc 、 c1

C、difference:

① different side chain of iron porphyrin.

  • Different linkage form of iron porphyrin with the protein.

CytFe3+ + e  CytFe2+


Chapter 4 biological oxidation

多聚异戊二烯长链

甲酰基


Chapter 4 biological oxidation

Difference between Cyt a and Cytb, Cytc.


Chapter 4 biological oxidation

(3) Complex Ⅲ Q-cytc reducase

  • i.e. cyt c reducase, consists of 11 peptide chains different, existing as a dimer. every monomer contains two cyt b (b562, b566), one cyt c1 and a iron sulphur protein.

  • Catalyze electron transfer from Q to cyt c. every two electrons’s transfering lead four proton pumped to the intermembrance space.

Cytc

QH2

b566b562Fe-Sc1


Chapter 4 biological oxidation

Cyt c

Complex Ⅲ


Chapter 4 biological oxidation

Electron transfering process in complexⅢ

first time oxidation of QH2

secondary time oxidation of QH2

Cytc

Cytc

2H+

2H+

Cytc1

Cytc1

Fe-S

Fe-S

e-

e-

bL

bL

e-

e-

QH2

Q

QH2

Q

bH

bH

Q

Q

QH2

Q

2H+


Chapter 4 biological oxidation

(4) complex Ⅳ

Cyt c oxidase

  • Dimer. Every monomer consists of 13 peptide chains different, as 3 subunits: I include 2 heme(a,a3),a cuproprotein (CuB);Ⅱinclude a dikaryon center formed by two copper ion(CuA);Ⅲ not clear

  • Cu2+ + e  Cu+

Cyt c

CuA a  a3  CuB

O2


Chapter 4 biological oxidation

NADH氧化呼吸链

NADHFMN(Fe-S)Qbc1caa3O2

琥珀酸氧化呼吸链

succinic acidFAD(Fe-S)Qbc1caa3O2


Chapter 4 biological oxidation

呼吸链

NADH + H+ + 1/2O2

NAD+ + H2O

呼吸链

FADH2 + 1/2O2

FAD + H2O

呼吸链

2H + 1/2O2

H2O

In FADH2 or NADH

overall reaction

or

further


Chapter 4 biological oxidation

呼吸链中电子传递体的排列顺序的确定

  • 利用脱氧胆酸处理线粒体内膜、分离出呼吸链的4种复合物,辅酶Q和细胞色素C及ATP合酶。

  • 根据标准氧还电位E0’的高低排列

  • 根据电子传递体氧化还原态时的吸收光谱变化进行检测

  • 利用阻断剂研究分析

  • 四种复合物的电子传递再造实验


Ii oxidative phosphorylation

II、oxidative phosphorylation

oxidative phosphorylation refer to the ATP producing form which the reaction ADP change into ATP couple withrespiratory chain oxidation. It is main form of ATP producing in body.


Chapter 4 biological oxidation

energy

ATP+H2O

30.5kJ/mol

ADP + Pi

energy level diagram

Why does the reaction: ADP + Pi  ATP + H2O request a couple?

The product state(ATP+H2O) is higher energy level than reactant state(ADP + Pi). So, ADP change into ATP isn’t spontaneous process. Energy obtaining is requested for the process.


Chapter 4 biological oxidation

  • Which segment in respiratory chain can produce enugh energy for ADP phosphorylation?


What s p o ratio what s its meaning

What’s P/O ratio?What’s its meaning?

--- number of moles of ATP produced as consuming a mole of oxygen atom in a reaction, i.e. the number of moles of phosphor cosumed when consume a mole of oxygen atom in the reaction.


Chapter 4 biological oxidation

1961~1978

  • What’s the way of ADPphosphorylation coupled with respiratory chain oxidation?

氧化磷酸化偶联机制有:化学物质偶联学说、构象偶联学说及化学渗透学说。目前公认度较大的是化学渗透学说。

Chemiosmotic hypothesis

  • the energy of respiratory chain oxidation change into proton gradient across the inner membrane.

  • the proton gradient drive ATP-synase produce ATP.


Chapter 4 biological oxidation

In electron transfer process, respiratory chain put proton to intermembrance of inner and outer membrance, result in proton concentration different of the two side of the inner membrance.


Chapter 4 biological oxidation

conceptual diagram of Chemiosmotic hypothesis

H+

H+

H+

H+

H+

H+

+ + + + + + + + + + + + + + + + + + +

- - - - - - - - - - - - - - -

e-

延胡素酸

H2O

NADH+H+

琥珀酸

1/2O2+2H+

NAD+

ATP

ADP+Pi


Chapter 4 biological oxidation

ATP synase

  • Consists of hydrophobic F0(a1b2c912)and hydrophilic F1(33).

  • When proton go straight through a,push c loop turning , and as a result, spur the F1 turning.


Chapter 4 biological oxidation

Position of ATP synase in mitochondria


Chapter 4 biological oxidation

松开

(O)

(O)

H+

结好

(L)

H+

脱水

(T)

H+

work principle of ATP synase

Three conformations of subunit:松L,紧T,放O

Procedure of ATP production:


Chapter 4 biological oxidation

Ⅲ. Factors affecting oxidation phosphorylation

  • Inhibitors

  • Regulation by ADP

  • Thyroid hormone

  • Mitchondrial DNA mutation


Chapter 4 biological oxidation

(1)Inhibitors

  • Inhibitors of respiratory chain

    blockelectron transfer of respiratory chain.

  • Uncoupler

    destroy the coupling of oxidation with phosphorylation, like uncoupling protein, 2,4-dinitrophenol.

  • Inhibitors of oxidative phosphorylation

    restrain the proton return to matrix side in ATP synase, like oligomycin


Chapter 4 biological oxidation

Blocking sites of inhibitorof respiratory chain

CO、CN-、N3-及H2S

抗霉素A

二巯基丙醇

异藤酮

粉蝶霉素A

异戊巴比妥


Chapter 4 biological oxidation

H+

H+

H+

Machanism of uncoupling

解偶联蛋白

H+

H+

ADP+Pi

ATP+H2O


Chapter 4 biological oxidation

寡霉素

inhibitory action of oligomycin

stop proton flow from F0 proton channel.


Chapter 4 biological oxidation

(2) regulation by ADP

main regulation factor:ADP/ATP ratio

ADP + Pi  ATP + H2O

Respiratory control ratio

离体线粒体实验,过量底物存在时,加入ADP后的耗氧速率与仅有底物时的耗氧速率之比


Chapter 4 biological oxidation

Na+-K+ ATP enzyme

ATP degradation

ADP/ATP

Oxidative phosphorylation

(3). Thyroid Hormone

Thyroid Hormone

甲状腺激素


Chapter 4 biological oxidation

(4) Mitchondrial DNA mutation

function ofmitochondrium

Mitochondrium diseases

  • all of the 13 peptides (7 peptides in NADHdehydrogenase, 1 in Cytcreducase, 3 in Cyt coxydase,2 in ATP synase coded) by Mitochondrium join in oxidative phosphorylation.

  • Mutation affectoxidative phosphorylation, ATP production decrease.

  • Naked cyclic duble helix DNA, lack of defend system and restoration system.

  • Symptoms are dependent on the degree of mutation and the different organs need for ATP.

  • Maternally inherited diseases (heritage neurosis, heritage diabetes and deafness)

  • Aging related


  • Iv mitochondria entry and exit of molecules

    IV、 Mitochondria Entry and Exit of Molecules

    Mitochondrial porin, the major protein of the outer mitochondrial membrane, allows molecules less than 10 kD to pass

    Inner membrance were controled by differnet transporter.


    Chapter 4 biological oxidation

    Oxidation of NADH in cytosol

    • α-glycerophosphate shuttle

      (α-磷酸甘油穿梭)

    • malate-asparate shuttle

      (苹果酸-天冬氨酸穿梭)


    Chapter 4 biological oxidation

    Comparison of the two ways of NADH oxidation


    Chapter 4 biological oxidation

    -磷酸甘油脱氢酶

    -磷酸甘油脱氢酶

    -glycerol phosphate shuttle

    呼吸链

    NADH+H+

    FADH2

    NAD+

    FAD


    Chapter 4 biological oxidation

    3ATP

    malate-asparate shuttle


    Aerobic dehydrogenase and oxydase

    Ⅰ. aerobic dehydrogenase and oxydase

    Section 3. other oxidationsystem


    Chapter 4 biological oxidation

    Ⅱ. Erzymes in peroxisome

    过氧化酶体中的酶类

    (1).catalase 过氧化氢酶

    • catalytic reaction: one molecule H2O2offer electron;another molecule H2O2accept electron.

    • prosthetic group: 4 heme

    • Function: wide distribution, wipe out toxical H2O2


    Chapter 4 biological oxidation

    (2). peroxidase (过氧化物酶)

    • Catalytic reaction:catalyze H2O2 straight oxidize phenols and amines

    • prosthetic group:1 heme

      Protect body. glutathione peroxidase

      Clinical diachorema occult blood test:


    Superoxide dimutase sod

    Ⅲ . superoxide dimutase, ( SOD,超氧化物歧化酶)

    呼吸链电子传递过程中产生超氧离子(O2-.)

    • O2-. H2O2 + .OH

    • 损伤生物膜、生成脂褐素

    SOD

    2O2-. + 2H+ H2O2 + O2

    H2O + O2

    过氧化氢酶

    SOD辅基含Cu、Zn(胞液)

    或Mn(线粒体)。


    1 monooxygenase

    RH+NADPH+H++O2 ROH+NADP++H2O

    (1). monooxygenase (加单氧酶)

    Ⅳ. Oxidases inmicrosome

    mixedfunction oxidase(混合功能氧化酶)

    or Hydroxylase(羟化酶).

    Catalytic reaction:

    composition: NADPH-Cytc reducase, flavoprotein(FAD), ironsulfur protein(Fe2S2)、CytP450。

    function:hydroxylation羟化。胆汁酸、胆固醇的生成;药物、毒物的转化;肾上腺皮质、类固醇激素的生物合成。


    Chapter 4 biological oxidation

    • mechanism

    RH.P450.Fe3+

    RH

    H2O

    ROH


    2 dioxygenases

    色氨酸吡咯酶 O2

    (2). dioxygenases (双加氧酶)

    incorporate both oxygen atoms into the substrate.


    Chapter 4 biological oxidation

    提要

    • ATP的生成主要通过氧化磷酸化。

    • 呼吸链是线粒体内膜中的一系列递氢和递电子酶及其辅酶按照一定顺序排列成的连锁性氧化还原体系。主要有两条:NADHFMN(FeS)Qbc1c aa3  O2

      琥珀酸FADH(FeS)Qbc1caa3O2

    • 呼吸链的电子传递与氧化磷酸化有三处偶联:NADHQ;CtybCytc;Cytaa3O2

    • 化学渗透假说

    • 影响氧化磷酸化的因素

    • 需氧脱氢酶、氧化酶、过氧化氢酶、过氧化物酶、SOD、羟化酶及加双氧酶的作用。


    Chapter 4 biological oxidation

    选择题练习

    生物氧化


    Chapter 4 biological oxidation

    1. 呼吸链存在于( )

    A 细胞膜

    B 线粒体外膜

    C 线粒体内膜

    D 微粒体

    E 过氧化物酶体


    Chapter 4 biological oxidation

    2. 下列哪种物质不是NADH氧化呼吸链的组分?

    A. FMN

    B. FAD

    C. 泛醌

    D. 铁硫蛋白

    E. 细胞色素c


    Chapter 4 biological oxidation

    3. ATP生成的主要方式是( )

    A 肌酸磷酸化

    B 氧化磷酸化

    C 糖的磷酸化

    D 底物水平磷酸化

    E 高能化合物之间的转化


    Chapter 4 biological oxidation

    4 由琥珀酸脱下的一对氢,经呼吸链氧化可产生( )分子ATP

    A 1

    B 2

    C 3

    D 4

    E 0


    Chapter 4 biological oxidation

    5 下例关于高能磷酸键的叙述,正确的是( )

    A 所有高能键都是磷酸键

    B 高能磷酸键只存在于ATP

    C 高能磷酸键仅在呼吸链中偶联

    D 有ATP参与的反应也可逆向进行

    E 所有的生化转变都需要ATP参与


    Chapter 4 biological oxidation

    6. 下列哪种酶以氧为受氢体催化底物氧化生成水?

    A 丙酮酸脱氢酶

    B 琥珀酸脱氢酶

    C 黄嘌呤氧化酶

    D 细胞色素c氧化酶

    E SOD


    Chapter 4 biological oxidation

    7. 关于线粒体内膜外H+浓度叙述正确的是( )

    A 浓度高于线粒体内

    B 浓度低于线粒体内

    C 可自由进入线粒体

    D 进入线粒体需主动转运

    E 进入线粒体需载体转运


    Chapter 4 biological oxidation

    8. 参与呼吸链电子传递的金属离子是( )

    A 铁离子

    B 钴离子

    C 镁离子

    D 锌离子

    E 以上都不是


    Chapter 4 biological oxidation

    9. 呼吸链中,不具有质子泵功能的是( )

    A 复合体Ⅰ

    B 复合体Ⅱ

    C 复合体Ⅲ

    D 复合体Ⅳ

    E 以上都不是


    Chapter 4 biological oxidation

    10. 关于超氧化物歧化酶,哪项是不正确的( )

    A 可催化产生超氧离子

    B 可消除超氧离子

    C 可催化产生过氧花氢

    D 含金属离子辅基

    E 存在于胞液和线粒体中


    Chapter 4 biological oxidation

    11. Except iron, Cyt aa3 contain ( ) ion.

    A Zn

    B Mg

    C Cu

    D Mn

    E K


    Chapter 4 biological oxidation

    12. Which one can be inhibited by CO in

    respiratory chain ?

    A FAD

    B FMN

    C Fe-S

    D Cyt aa3

    E Cyt c


    Chapter 4 biological oxidation

    13. Which one is uncoupler?

    A CO

    B piericidin A

    C KCN

    D 2,4-dinitrophenol

    E H2S


    Chapter 4 biological oxidation

    14. The right electron tansferation sequence is ( )

    A b→c→c1→aa3→O2

    B c1→c→b→aa3→O2

    C c→c1→b→aa3→O2

    D c→b→c1→aa3→O2

    E b→c1→c→aa3→O2


    Chapter 4 biological oxidation

    15. 关于ATP合成酶,叙述正确的是( )

    A 位于线粒体内膜,又称复合体Ⅴ

    B 由F1和F0两部分组成

    C F0是质子通道

    D 生成ATP的催化部位在F1的亚基上

    E F1呈疏水性,嵌在线粒体内膜中


    Chapter 4 biological oxidation

    16. 关于辅酶Q, 哪些叙述是正确的?

    A 是一种水溶性化合物

    B 其属醌类化合物

    C 可在线粒体内膜中迅速扩散

    D 不参与呼吸链复合体

    E 是NADH呼吸链与琥珀酸呼吸链的交汇点


    Chapter 4 biological oxidation

    17. 关于细胞色素,叙述正确的是( )

    A 均以铁卟啉为辅基

    B 有色

    C 均为电子传递体

    D 均可被氰化物抑制

    E 本质是蛋白质


    Chapter 4 biological oxidation

    18. 下列物质属于高能化合物的是( )

    A 乙酰辅酶A

    B GTP

    C 磷酸肌酸

    D 磷酸二羟丙酮

    E 磷酸烯醇式丙酮酸


    Chapter 4 biological oxidation

    19. Which make Fe-S as prosthetic group in the respiratory chain?

    A Complex Ⅰ

    B Complex Ⅱ

    C Complex Ⅲ

    D Complex Ⅳ

    E Cyt c


    Chapter 4 biological oxidation

    20. Where does the phosphorylation couple with the oxidation and can produce ATP?

    A NADH→CoQ

    B CoQ→Cyt b

    C CoQ→Cyt c

    D FADH2→CoQ

    E Cyt aa3→O2


    Chapter 4 biological oxidation

    论述题:

    1 试述生物氧化与体外物质氧化的异同。

    2 试述影响氧化磷酸化的因素及其作用机制。


    Chapter 4 biological oxidation

    名词解释:

    呼吸链

    氧化磷酸化。


    Chapter 4 biological oxidation

    谢谢!


  • Login