electron transport chain

25
Department of Biochemistry, NGMC, Chisapani, Nepal Thursday, September 15, 2016 Rajesh Chaudhary 1 http://www.slideshare.net/RajeshChaudhary10 Note / Remember

Upload: nepalgunj-medical-college-and-teaching-hospital

Post on 14-Apr-2017

223 views

Category:

Science


1 download

TRANSCRIPT

Department of Biochemistry, NGMC, Chisapani, Nepal

Thursday,

September 15,

2016Rajesh Chaudhary

1

http://www.slideshare.net/RajeshChaudhary10

Note / Remember

Biomedical importance

Oxidative phosphorylation (OXPHOS) is essential for

generation of high energy intermediate – ATP.

Inhibition of OXPHOS results into fatal consequences –

myopathy, encephalopathy and lactic acidosis.

Drugs and poisons that inhibits OXPHOS: amobarbital,

cyanide, carbon monoxide.

Thursday,

September 15,

2016Rajesh Chaudhary

2

The system in mitochondria that couples respiration to

generation of high energy intermediate, ATP, is termed as

Oxidative Phosphorylation (OXPHOS).

Thursday,

September 15,

2016Rajesh Chaudhary

3

— Harper’s Biochemistry, 25th. Edition

Respiratory chain collects & oxidizes

reducing equivalents

Thursday,

September 15,

2016Rajesh Chaudhary

4

Phases of metabolism

Thursday,

September 15,

2016Rajesh Chaudhary

5

Phases

metabolism

1. Primary

2. Secondary /

Intermediate

3. Tertiary

Electron transfer reaction in

mitochondria

6

Mitochondria and Oxidative

phosphorylation

The transfer of electron is done by the set of protein

complexes.

Thursday,

September 15,

2016Rajesh Chaudhary

7

Outer mitochondrial membrane

Mitochondrial matrix

The mitochondrial matrix enclosed by the inner membrane,

contains the pyruvate dehydrogenase complex and the

enzymes of the citric acid cycle, the fatty acid b-oxidation

pathway, and the pathways of amino acid oxidation – all

the pathways of fuel oxidation except glycolysis, which takes

place in cytosol.

Thursday,

September 15,

2016Rajesh Chaudhary

8

— Lehninger’s Principle of Biochemistry, 5th. Edition

Mitochondria and Oxidative

phosphorylation

Mitochondria is the site of oxidative phosphorylation.

Oxidative phosphorylation (OXPHOS): metabolic pathways in

which cells use enzymes to oxidize nutrients thereby releasing

energy which is used to reform ATP.

Takes place inside mitochondria.

During OXPHOS, electrons are transferred from donor to acceptor.

Thursday,

September 15,

2016Rajesh Chaudhary

9

Electrons are funneled to universal electron

acceptor

Oxidative phosphorylation beings with the entry of electrons

into the respiratory chain.

Most of these electrons arise from the action of

dehydrogenases that collect electrons from catabolic

pathways and funnel them into universal electron

acceptors – nicotinamide nucleotide (NAD+ or NADP+) of

Flavin nucleotides (FMN or FAD).

Thursday,

September 15,

2016Rajesh Chaudhary

10

Malate-Aspartate shuttle

Thursday,

September 15,

2016Rajesh Chaudhary

11

Requirements for ATP generation from

OXPHOS

1. An electron donor: NADH and/or FAD(2H)

2. An electron acceptor: O2

3. Intact inner mitochondrial membrane that is impermeable to

protons.

4. All components of electron transport chain.

5. ATP synthase

Thursday,

September 15,

2016Rajesh Chaudhary

12

Oxidative phosphorylation is regulated by the rate of ATP utilization !

1. Complex I / NADH

dehydrogenase

2. Complex II / Succinate

dehydrogenase

3. Complex III / Cytochrome b-C1

4. Complex IV / Cytochrome C

oxidase

5. Complex V / ATP synthase

Components of Electron Transport

Chain (ETC)

Thursday,

September 15,

2016Rajesh Chaudhary

13

Components of ETC

Major components of ETC

Thursday,

September 15,

2016Rajesh Chaudhary

14

Complex III

ETC also contains:

1. Coenzyme Q

2. Cytochrome C

With the exception of Coenzyme Q

(CoQ) rest are proteins in ETC !

Thursday,

September 15,

2016Rajesh Chaudhary

15

Electron Transport Chain (ETC)

Thursday,

September 15,

2016Rajesh Chaudhary

16

Chemiosmotic model of ATP generation

Thursday,

September 15,

2016Rajesh Chaudhary

17

Components of ETC

Thursday,

September 15,

2016Rajesh Chaudhary

18

Coenzyme Q

The only component of ETC that is not protein bound.

Large hydrophobic side chain of 10 isoprenoid units (50

carbons) confers lipid solubility.

It is also called Ubiquinone.

Thursday,

September 15,

2016Rajesh Chaudhary

19

Adenosine Triphosphate Synthase

(ATP synthase)

Thursday,

September 15,

2016Rajesh Chaudhary

20

Also known as

F0F1 ATPase

Stalk

Binding-change mechanism for ATP

synthesis

Thursday,

September 15,

2016Rajesh Chaudhary

21

Link for the video down below: https://www.youtube.com/watch?v=3y1dO4nNaKY

Electrons pass through series of membrane-

bound carriers

Usually carrier molecules are integral proteins with prosthetic

group capable of accepting and donating one or two

electrons.

Types of electron transfer in OXPHOS

1. Direct transfer of electrons, as in the reduction of Fe3+ to Fe2+.

2. Transfer as a hydrogen atom (H+ + e-).

3. Transfer as hydride ion which bears two electrons (:H-).

Thursday,

September 15,

2016Rajesh Chaudhary

22

Summary of flow of electrons and protons

through four complexes of the respiratory

chain

Thursday,

September 15,

2016Rajesh Chaudhary

23

Proposed sites of inhibition

Thursday,

September 15,

2016Rajesh Chaudhary

24

References

Thursday,

September 15,

2016

Rajesh Chaudhary

25