Catalysts of Lipid Oxidation
Iron
The most important nonenzymic catalyst for initiation of
lipid peroxidation
The most abundant transitional metal in biological systems
Possibility of various oxidation states (from –II to +VI),
the forms of Fe(II) and Fe(III) is dominated in biological
systems
Role of iron and other metal ions in converting less
reactive to more reactive species
O2- + H2O2 + Fe -----> .OH
(Iron-catalyzed Haber-Weiss reaction)
Lipid peroxides (ROOH) -----> ROO., RO., cytotoxic aldehydes (4hydroxyl-2,3-trans-nonenal, malondialdehyde)
Thiols (RSH) + Fe/Cu + O2 -----> O2-, H2O2, .OH, thiyl (RS.) + O2 ----->
thiyl peroxyl (RSO2.), RSO. (sulfenyl)
NAD(P)H + Fe/Cu + O2 -----> NAD(P)., H2O2, O2-, .OH
Ascorbic acid + Fe/Cu -----> semidehydroxy ascorbate radical, H2O2,
.OH
Catecholamines, related autoxidazable molecules Fe/Cu + O2 ----->
H2O2, O2-, .OH, semiquinones
Structural Iron
Hb: 2/3 of total body iron
Mb: muscle pigment. Most abundant heme pigment in
meat
Cytochrome c: electron transport chain
Catalase: antioxidant enzyme
Heme Irons
Ferrous heme pigment
Ferric heme pigment
Ferryl complexes
Hematin
Heating or addition of H2O2 caused the release of heme
iron due to oxidative cleavage of porphyrin ring of heme
Formation of reactive species by interaction
of Hb with H2O2
Hemoglobin
access H2O2
(Ferryl?)
Stimulation of
lipid peroxidation
heme degradation
iron ion release
H2O2
.OH
other tissue damage
Hematin
Is released from myoglobin before the release of free ionic
iron in the presence of H2O2
Hematin can catalyze lipid peroxidation more efficiently
than ionic iron because hematin is more reactive than
hemeproteins and ferrous ion
Is hydrophobicity allows it to permeate into membrane
easily.
Hematin monomer and hematin with hypervalent iron
(FeIV=O) can initiate lipid oxidation.
Storage and Transport iron
- Tightly bound iron
- Ovotransferrin
- Ferritin
- Homosiderin
Loosely Bound Iron
low molecular weight chelators
2.4~3.9% of total iron
Depending on animal species and muscle types
Concentration can be influenced by heating, the presence
of ascorbic acid and H2O2 and storage
Organic phosphate esters (e.g. NAD(P)H, AMP, ADP, and
ATP)
Inorganic phosphates
Amino acids
Organic acids (e.g. citrate)
Free Ionic Iron
Plays an important role in the catalysis of lipid peroxidation
Fe(III) catalyzed lipid peroxidation only in the presence of
ascorbic acid
Hydrogen peroxide (H2O2) and ascorbate can release free
iron from heme pigments and ferritin
Transferrin- and ferritin-bound irons nor heme pigments
had any catalytic effect in raw muscle.
Biological iron complexes and their possible
participation in oxygen radical reactions
Type of iron complexes
Loosely bound iron
Iron ion attached to phosphate
Esters (ATP etc.)
Carbohydrates and organic acids
(e.g., citrate, deoxiribose)
DNA
Membrane lipids
Mineral ores (asbestos, silicates)
Decomposition of lipid
peroxides to form alkoxyl
and peroxyl radicals
Hydroxyl radical
formation by
Fenton chemistry
Yes
Yes
Yes
Yes
Probably yes
Yes
Yes
Yes
Yes
Yes
Iron tightly bound to proteins
Nonheme iron
Ferritin (4500 mol Fe/mol protein)
Hemosiderin
Lactoferrin (2 mol Fe3+/mol protein)
Transferrin (2 mol Fe2+/mol protein)
Yes
Yes (when iron is released)
Weakly (when iron is released) Weakly (whe iron is released)
No
No
No
No
Heme iron
Hemoglobin
Myoglobin
Cytochrome c
Catalase
Yes (when iron is released)
Yes (when iron is released)
Yes (when iron is released)
Weakly
Yes
Yes
Yes
Not
(when iron is released)
(when iron is released)
(when iron is released)
observed
Products of Lipid Oxidation
Products of Lipid Oxidation
Oxidation of diene lipids
Oxidation of triene lipids
Autoxidation
9-OOH D10,12,15 (37%)
Photo-oxidation
9-OOH D10,12,15 (23%)
10-OOH D8,12,15 (13%)
12-OOH D9,13,15 (8%)
12-OOH D9,13,15 (12%)
13-OOH D9,11,15 (10%)
13-OOH D9,11,15 (14%)
15-OOH D9,12,16 (13%)
16-OOH D9,12,14 (45%)
16-OOH D9,12,14 (25%)
Oxidation of triene lipids
Oxidation of highly unsaturated lipids
Oxidation of highly unsaturated lipids
Secondary Peroxidation Products from
Fatty Acids
Hydrocarbons: Alkanes and Alkenes
C8-OOH oleate
Homolysis
Homolytic beta-scission of a carbon bond on either
side of the O-containing carbon atom
Addition
Alkanes, Alkenes
C8-hydroperoxide of oleic acid (8-OOH oleate): 1-decene
C9-hydroperoxide of oleic acid (9-OOH oleate): 1-nonene
C10-hydroperoxide of oleic acid (10-OOH oleate): 1-octene
C13-hydroperoxide of linoleic and arachidonic acid:
pentane produce pentane
C13-hydroperoxide of linoleic acid produces ethane and
ethylene
Aldehydes
From C8-OOH oleate
A
CH3(CH2)7CH=CH-CH-(CH2)6-COOH
O.
Aldehydes from n-6 fatty acids
Peroxidation of n-6 fatty acids (linoleic and arachidonic
acid):
9-hydroperoxy linoleate: 2,4-decadienal, and 3-nonenal
13-hydroperoxy linoleate: hexanal and pentanal
10-hydroperoxy linoleate: 2-heptenal
Other volatile aldehydes formed: 2-hexenal, 2-octenal, 2,4nonadienal, 4,5-hydroxydecenal, 4-hydroxy-2,3-transnonenal
4-HNE formation
13-hydroperoxy
linoleic acid (13-HPODE)
Reduction
H-abstraction
isomerization
oxidation
cleavage
4-Hydroxy-2,3-trans nonenal (4HNE)
Formed by linoleate, arachidonic acid oxidation
Have high cytotoxicity at high concentrations
Inhibits DNA and protein synthesis and generate
oxidative stress
Act in defense against fungi in plants
At low concentrations, have chemotactic effect, stimulate
guanylate cyclase and phospholipase C activities
Aldehydes from n-3 fatty acids
Peroxidation of n-3 fatty acids (linolenic and EPA, DHA):
Various compounds depending upon the location of
hydroperoxy group
9-OOH linolenate: 2,4,7-decatrienal, 3,6-nonadienal
12-OOH linolenate: 2,4-heptadienal, 3-hexenal
13-OOH linolenate: 3-hexenal and 2-pentenal
16-OOH linolenate: propanal
Other volatile aldehydes formed: butanal, 4,5-epoxy hepta2-enal, 4-hydroperoxy hexenal, 4,5-hydroxydecenal, 4hydroxy-2,3-trans-hexenal
Malonaldehyde
Formed by further degradation of hydroperoxy aldehydes
The main precursor: monocyclic peroxides formed from
fatty acids with 3 or more double bonds
Introduces cross-links in proteins and induces profound
alteration in their biochemical properties
Epoxides (or Oxirane oxygen)
Linoleic epoxides
Epoxides
Generated by the attack of any double bonds present in
fatty acid chain by a lipid peroxyl radical (ROO.)
Toxic
Some of them (epoxyeicosatrienoic acid) affects blood flow,
mitogenesis, platelate aggregation, anti-inflamatory,
vasoregulation (relax renal arteries)
Volatile compounds produced from arachidonic acid
1-Pentene
Pentane
1-Methoxy-2-methyl-1-propene
2-Methyl pentane
3-Methyl pentane
2,2-Dimethyl pentane
2,3-Dimethyl pentane
3,3-Dimethyl pentane
1-Hexene
Hexane
2-Methyl hexane
3-Methyl hexane
3-Ethyl hexane
2,4-Dimethyl hexane
1-Octene
Octane
2-Octene
3-Octene
3-Methyl octane
2,6-Dimethyl octane
1-Heptene
Heptane
2,6-Dimethyl heptane
1,2,4-Trimethyl heptane
Ethyl benzene
1,3-Dimethyl benzene
2,2,3-Trimethyl butane
3-Nonen-1-ol
Undecanenitrile
Octahydro-1H-indene
1,3-Cyclopentadiene
4-Methyl cyclopentene
3-Methyl cyclopentene
Methyl cyclopentane
1,1,3-Trimethyl cyclopentane
Cyclohexane
Cyclohexene
Methyl cyclohexane
1,3-Dimethyl cylohexane
Ethyl cyclohexane
1,1,3-Trimethyl cyclohexane
1,2,4-Trimethyl cyclohexane
1,2,3,5-Tetramethyl cyclohexane
1-Ethyl-3-methyl cyclohexane
Propyl cyclohexane
1-Ethyl-2,3-dimethyl cyclohexane
Butyl cyclohexane
1,1,2,3-Tetramethyl cyclohexane
1-Methyl-4-(1-methylethyl)-cyclohexane
1,1,4-Trimethyl cyclohexane
1,2-Dimethyl cyclooctane