17. biological oxidation

BIOLOGICAL

OXIDATION

Biological oxidation is the process in which

substances (carbohydrate, Lipid, AAs)

are oxidized in living organism.

Oxidation types:

Dehydrogenation

Electron lost

Oxygenation

Nature of biological oxidation ：

1. 37℃, pH 7.4, enzymatic reaction.

2. Energy released gradually.

3. Formation of H2O.

4. Formation of CO2 by decarboxylation.

CO2

ATP ADP + Pi1/2 O2

H2O

acetyl CoA CoASH

G glycerol, FAs AAs

glycogen lipids proteinsfirst

phase

secondphase

thirdphaseoxidative

phosphorylation

Pyr

TCAC

cytosol

Mit.

2H

2H

General situation of biological oxidation

§1 Respiratory Chain

§2 Oxidative

Phosphorylation

§3 ATP

§4 Shuttle Systems

§ 1 Respiratory Chain

A chain in the mitochondria consists of a number of redox carriers for transferring hydrogens removed from the substrate to oxygen to form water. The chain is termed a respiratory chain, also called electron transport chain (ETC).

COMPOSITION OF RESPIRATORY CHAIN COMPLEXES

Complexes NameProsthetic Groups

Complex I NADH-CoQ Reductase

FMN, Fe-S

Complex II Succinate-CoQ Reductase

FAD, Fe-S

Complex III CoQ-Cyt c Reductase

iron-porphyrine

Fe-S

Complex IV Cytochrome Oxidase

iron-porphyrine Cu

Position of Respiratory Chain Complexes

Order of Respiratory Chain Complexes

NADH

succinate

FMN£¨Fe-S£©

FAD£¨Fe-S£©

Cyt b, £¨Fe-S£©CoQ Cyt aa3 O2Cyt ccompex I

compex II

compex III compex IV

c1

Composition of ETC

　　 Hydrogen carrier ： NAD + 　　　　　　　 FMN　　　　　　　 FAD　　　　　　　 CoQ

　　 electron carrier ： Fe-S 　　　

　　　　　　　　　　 Cyt

NAD+/NADH (Nicotinamide Adenine Dinucleotide, CoⅠ)

NADP+/NADPH (Nicotinamide Adenine Dinucleotide Phosphate, CoⅡ)

The nicotinamide is the vitamin Niacin B3

1. Nicotinamide coenzymes

NAD+

O

H H

OH OH

H H

CH2 O O

OHOH

HHH

CH2

H

OP

OH

O

N

N

N

N

NH2

N

CONH2

O P

OH

O

NADP+

O

H H

OH OH

H H

CH2 O O

OOH

HHH

CH2

H

OP

OH

O

N

N

N

N

NH2

N

CONH2

O P

OH

O

PO

OH

OH

N

H

CONH2

R

+ H + H + + e

N

H

CONH2

R

H

+ H +

NAD +/NADP + NADH/NADPH

FMN: Flavin Mononucleotide

FAD: Flavin Adenine Dinucleotide

They contain the riboflavin

(Vit B2).

2. Flavin prosthetic groups

FMN

CH2 OHO P

OH

OC

C

H OH

C

H OH

H OH

CH H

NH

N

N

N O

O

H3C

H3C1

45

8 9

10Isoalloxazine

ribitol

FAD

CH2 O O

OHOH

HHH

CH2

H

OP

OH

O

N

N

N

N

NH2

O P

OH

OC

C

H OH

C

H OH

H OH

CH H

NH

N

N

N O

O

H3C

H3C1

45

8 9

10

R

NH

N

N

N O

O

H3C

H3C

FMN/FAD

1

45

8 9

10

R

NH

NH

HN

N O

O

H3C

H3C1

45

8 9

10+ 2H

FMNH2/FADH2

NAD+ is a coenzyme, that reversibly binds to enzymes.

FAD is a prosthetic group, that remains tightly bound at the active site of an enzyme.

Iron-sulfur centers (Iron-sulfur protein, Fe-S) are prosthetic groups containing 2, 3, 4 or 8 nonheme iron atoms complexed to elemental and cysteine S.

3. Fe-S

Fe

Fe

S

S

S

Fe

Fe

S

S

S

SS

Cys

Cys

Cys

Cys

S

Fe

S

Fe

S

S

S

S

Cys

CysCys

Cys

Iron-sulfur centers

2 Fe iron-sulfur center of ferredoxin.

2 Fe colored orange; elemental & Cys S yellow.

Different types of iron-sulfur centers

Iron-sulfur centers transfer only one electron.

Fe3+ + e- Fe2+

Coenzyme Q (CoQ, ubiquinone) is very hydrophobic. It dissolves in the membrane.

Coenzyme Q functions as a mobile e- carrier within the mitochondrial inner membrane.

4. CoQ

isoprene

H2C C C CH2

CH3

H

O

O

H3CO

H3CO

CH3

(CH2 CH

C

CH3

CH2)nH

CoQ

O

O

CH3O

CH3CH3O

R

OH

OH

CH3O

CH3CH3O

R

+ 2H

ubiquinone ubiquinol

Cytochromes (Cyt) are proteins with heme prosthetic groups. They absorb light at characteristic wavelengths.

Hemes in the 3 classes of cytochrome (a, b, c) differ slightly in substituents on the porphyrin ring system.

5. Cytochromes

Hemes a & a3 are often referred to as cytochromes aa3.

Cytochrome c is a small, water-soluble protein with a single heme group.

N

N

N

N

CH3 CH

CH2

CH3

CH CH2

CH2

CH2

COO

CH3

HC

CH2CH2 OOC

Fe

O

Heme b

N

N

N

N

CH3 HC

CH3

S CH2

CH3

CH S CH2

CH3

CH2

CH2

COO

CH3

H3C

CH2CH2 OOC

protein

protein

Fe

Heme c

Heme c

Cytochrome c

Lys13 Lys 72

heme

complex IV

cyt. c

N

N

N

N

CH3 HC

CH2

CH3

CH CH2

CH2

CH2

COO

CH3

HC

CH2CH2 OOC

Fe

OH

CH2 CH C CH2

CH3

3 H

O

Heme a

The heme iron can undergo an electron transition between ferric and ferrous states:

Fe3+ + e- Fe2+

The sequence of the components in the respiratory chain has been deduced in several ways.

1. Inhibitor.

2. O2 is suddenly introduced into the system.

3. Standard redox potential.

INHIBITOR

NADH FMN£¨Fe-S£©

c1 c aa3 O2

FAD£¨Fe-S£©

succinate¦Á-glycerophosphate

CoQ Cyt b

malate¦Â-hydroxy fatty acyl CoA¦Â-hydroxybutyrateisocitriteGlu

FAD

lipoic acid

pyruvate¦Á-ketoglutarate

FAD

fatty acyl CoA

17. biological oxidation

Technology

Transcript of 17. biological oxidation