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BIOLOGICAL OXIDATION Dr. Dalia Shaalan Lecturer of Medical Biochemistry Faculty of Medicine Mansoura University

BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

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Page 1: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

BIOLOGICAL OXIDATION

Dr. Dalia Shaalan

Lecturer of Medical Biochemistry

Faculty of Medicine – Mansoura University

Page 2: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

BIOLOGICAL OXIDATION

• Biological oxidation is oxidation which occurs in

biological systems to produce energy.

• Energy required to maintain the structure and

function of the living cells.

• Energy is produced by oxidation of food stuffs

e.g. glucose, FA, AA.

Page 3: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

BIOLOGICAL OXIDATION

Oxidation can occur by:

1. Addition of oxygen (less common)

2. Removal of hydrogen (common)

3. Removal of electrons (most common)

Page 4: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

BIOLOGICAL OXIDATION

• Electrons are not stable in the free state.

• Electrons removal (oxidation) should paired with

electron acceptance (reduction) by another

substance.

• Oxidation-reduction reactions or redox reactions

are done by oxido-reductases.

Page 5: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

BIOLOGICAL OXIDATION

Redox potential :

It is the affinity of a substance to accept

electrons (= to be reduced).

Oxygen (+0.82 volt) (highest)

Hydrogen (-0.42 volt) (lowest)

All other substances lie in between

Page 6: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

BIOLOGICAL OXIDATION

Redox potential:

• Electrons are transferred from substances with

low redox potential to substances with higher

redox potential.

• Electrons transfer is an energy yielding process.

• The amount of energy liberated depends on the

redox potential difference between the electron

donor and acceptor.

Page 7: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductases

• Enzymes catalyze oxidation- reduction reactions

• Classified into:

1. Oxidases,

2. Aerobic dehydrogenases,

3. Anaerobic dehydrogenases,

4. Hydroperoxidases

5. Oxygenases

Page 8: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductases

1. Oxidases :

• Conjugated proteins containing copper.

• Catalyze removal of hydrogen from substrates

and use oxygen only as hydrogen acceptor

forming water except uricase and monoamine

oxidase form hydrogen peroxide.

AH2 O2

A H2O2

AH2 ½ O2

A H2O

Oxidase Uricase

Page 9: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductases

1. Oxidases :

• Cannot use artificial substrate (dye) as hydrogen

acceptor.

• Examples:

• Ascorbic acid oxidase,

• Polyphenol oxidase,

• Cytochrome oxidase.

Page 10: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductases

2. Aerobic Dehydrogenases :

• Flavin-linked enzymes (flavoproteins) that need

FAD or FMN as coenzymes.

• The coenzyme of aerobic dehydrogenases:

1. FMN as in L-amino acid oxidase.

2. FAD as in D-amino acid oxidase, xanthine

oxidase, aldehyde dehydrogenase and

glucose oxidase.

Page 11: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductases2. Aerobic Dehydrogenases :

• Catalyze direct transfer of hydrogen from

substrates to oxygen forming hydrogen peroxide

(H2O2).

• Can use artificial substrate (dye) as hydrogen

acceptor.

AH2 Dye

A reduced dye

AH2 O2

A H2O2

Aerobic

dehydrogenase

Aerobic

dehydrogenase

Page 12: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductases

3. Anaerobic Dehydrogenases :

• Catalyze removal of hydrogen from substrate but

cannot transfer hydrogen directly to oxygen.

• Hydrogen is indirectly transferred to oxygen or

to artificial substrate (dye) through more than

one carrier.

Reduced

Carrier 1

H2 O

(or reduced dye)

½ O2

(or dye )

Oxidized

Carrier 2

AH2

A

Aerobic

dehydrogenase

Oxidized

Carrier 1

Reduced

Carrier 2

Oxidized

Carrier 3

Reduced

Carrier 3

Page 13: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductases3. Anaerobic Dehydrogenases (acc. to coenzymes):

a) Cytoplasmic glycerol-3-phosphate dehydrogenase

b) Isocitrate dehydrogenase.

c) Malate dehydrogenase.

d) β- Hydroxy acyl CoA dehydrogenase.

e) β- Hydroxy butyrate dehydrogenase.

NAD+ linked anaerobic

dehydrogenases

a)Glucose-6-phosphate dehydrogenase.

b)Malic enzyme.

c)Cytoplasmic isocitrate dehydrogenase.

NADP linked anaerobic

dehydrogenases

a)Succinate dehydrogenase.

b)Mitochondrial glycerol-3-phosphate dehydrogenase.

c)Acyl CoA dehydrogenase.

FAD linked anaerobic

dehydrogenases

which is present in the respiratory chain.Ubiquinol (coenzyme

Q) dehydrogenase

All cytochromes are anaerobic dehydrogenases except

cytochrome oxidase (cyt a3), which is an oxidase and

cytochrome P450 that is mono-oxygenase (hydroxylase).

Cytochromes

Page 14: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductases

4. Hydroperoxidases

• Use hydrogen peroxide (H2O2) as substrate

changing it into water to get rid of its harmful

effects.

• They are further classified into peroxidases and

catalases.

Page 15: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductases

4. Hydroperoxidases

a) Peroxidases: need a reduced substrate as hydrogen donor.

H2O2 + XH2 2H2O + X

reduced substrate oxidized substrate

• Glutathione peroxidase gets rid of H2O2 from red cells to

protect them from haemolysis.

H2O2 + 2 G-SH 2H2O + G-S-S-G

reduced glutathione oxidized glutathione

Peroxidase

Peroxidase Glutathione

Page 16: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductases

4. Hydroperoxidases

b) Catalases: act on 2 molecules of hydrogen

peroxide other molecule is the hydrogen donor.

Catalase

2H2O2 2H2O + O2

Page 17: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductases

AH2 A

Aerobic

dehydrogenases

and some oxidases

_ _

O2 + O2

Superoxide dismutase

H2 O2

H2O2O2 2H2O

H2O2

Peroxidase

Catalase

O2

XH2 X

Hydrogen peroxide metabolism

Page 18: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductases5. Oxygenases

• Catalyze direct incorporation (addition) of oxygen

into substrate. They are either di- or mono-

oxygenases.

A. Dioxygenases (true oxgenases):

Incorporate two atoms of oxygen molecule into

substrate e.g. tryptophan pyrrolase, homogentisic

acid dioxygenase, carotenase.

Page 19: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductases5. Oxgenases

B. Mono-oxygenases (pseudo-oxygenases;

hydroxylases; mixed function oxygenases)

• Incorporate one oxygen atom into substrate and the

other atom of the oxygen molecule is reduced to

water. e.g. phenylalanine hydroxylase, tyrosinase

and cytochrome P450.

Page 20: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductases

5. Oxgenases: B. Mono-oxygenases

Cytochrome P450

• A group of hydroxylases which are collectively referred to

as cytochrome P450.

• Their reduced forms exhibit an intense absorption band at

wavelength 450 nm when complexed to carbon monoxide.

• They are conjugated protein containing haeme

(haemoproteins).

Page 21: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductasesCytochrome P450

According to their intracellular localization they may be :

1. Microsomal cytochrome P450:

mainly in the microsomes of liver cells (about 14% of the

microsomal fraction of liver cells).

2. Mitochondrial cytochrome P450:

in mitochondria of many tissues but it is particularly

abundant in liver and steroidogenic tissues as adrenal

cortex, testis, ovary, placenta and kidney.

Page 22: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

Oxido-reductases

Functions of microsomal cytochrome P450

1. Detoxication of xenobiotics by hydroxylation. e.g.

insecticides,carcinogens,mutagens and drugs.

2. Metabolism of some drugs by hydroxylation e.g.

morphine, aminopyrine, benzpyrine and aniline.

microsomal

drug-H + O2 + XH2 drug-OH + H2O + X

Cytochrome P450

Page 23: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the

• +OH at C20, C22 (in side chain

cleavage of cholesterol).

• +OH at C11 by 11-hydroxylase.

• +OH at C18 by 18-hydroxylase.

adrenal cortex,

testis, ovary ,

placenta

1. Biosynthesis of

steroid hormones

from cholesterol

• +OH at C26 by 26-hydroxylase.liver

2. Biosynthesis of

bile acids from

cholesterol

• +OH at C25 by 25-hydroxylase .

• +OH at C1 by 1-hydroxylase.

• +OH at C24 by 24-hydroxylase

liver

kidney

kidney

3. Activation of

vitamin D

Function of mitochondrial cytochrome P450

Page 24: BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which occurs in biological systems to produce energy. • Energy required to maintain the