BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which...
Transcript of BIOLOGICAL OXIDATION - Mans · BIOLOGICAL OXIDATION • Biological oxidation is oxidation which...
BIOLOGICAL OXIDATION
Dr. Dalia Shaalan
Lecturer of Medical Biochemistry
Faculty of Medicine – Mansoura University
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.
BIOLOGICAL OXIDATION
Oxidation can occur by:
1. Addition of oxygen (less common)
2. Removal of hydrogen (common)
3. Removal of electrons (most common)
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.
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
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.
Oxido-reductases
• Enzymes catalyze oxidation- reduction reactions
• Classified into:
1. Oxidases,
2. Aerobic dehydrogenases,
3. Anaerobic dehydrogenases,
4. Hydroperoxidases
5. Oxygenases
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
Oxido-reductases
1. Oxidases :
• Cannot use artificial substrate (dye) as hydrogen
acceptor.
• Examples:
• Ascorbic acid oxidase,
• Polyphenol oxidase,
• Cytochrome oxidase.
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.
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
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
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
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.
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
Oxido-reductases
4. Hydroperoxidases
b) Catalases: act on 2 molecules of hydrogen
peroxide other molecule is the hydrogen donor.
Catalase
2H2O2 2H2O + O2
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
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.
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.
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).
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.
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
• +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