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Catalysts of Lipid Oxidation

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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- + H2 O2 + Fe -----> .OH (Iron-catalyzed Haber-Weiss reaction)

Lipid peroxides (ROOH) -----> ROO., RO., cytotoxic aldehydes (4- hydroxyl-2,3-trans-nonenal, malondialdehyde)

Thiols (RSH) + Fe/Cu + O2 -----> O2-, H2 O2 , .OH, thiyl (RS.) + O2 ----->

thiyl peroxyl (RSO2.), RSO. (sulfenyl)

NAD(P)H + Fe/Cu + O2 -----> NAD(P)., H2 O2 , O2-, .OH

Ascorbic acid + Fe/Cu -----> semidehydroxy ascorbate radical, H2 O2 , .OH

Catecholamines, related autoxidazable molecules Fe/Cu + O2 -----> H2 O2 , 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 pigmentFerric heme pigmentFerryl complexesHematinHeating or addition of H2 O2 caused the release of heme

iron due to oxidative cleavage of porphyrin ring of heme

Formation of reactive species by interaction of Hb with H2 O2

Hemoglobin

access H2 O2

(Ferryl?) heme degradation

Stimulation of iron ion release lipid peroxidation

H2 O2

.OH other tissue damage

Hematin

Is released from myoglobin before the release of free ionic iron in the presence of H2 O2

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 chelators2.4~3.9% of total ironDepending on animal species and muscle typesConcentration can be influenced by heating, the presence

of ascorbic acid and H2 O2 and storage Organic phosphate esters (e.g. NAD(P)H, AMP, ADP, and ATP)Inorganic phosphatesAmino acidsOrganic acids (e.g. citrate)

Free Ionic Iron

Plays an important role in the catalysis of lipid peroxidationFe(III) catalyzed lipid peroxidation only in the presence of

ascorbic acid Hydrogen peroxide (H2 O2 ) and ascorbate can release free

iron from heme pigments and ferritinTransferrin- 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

Decomposition of lipid Hydroxyl radical peroxides to form alkoxyl formation by

Type of iron complexes and peroxyl radicals Fenton chemistryLoosely bound iron

Iron ion attached to phosphate Yes YesEsters (ATP etc.)Carbohydrates and organic acids Yes Yes(e.g., citrate, deoxiribose)

DNA Probably yes YesMembrane lipids Yes YesMineral ores (asbestos, silicates) Yes Yes

Iron tightly bound to proteinsNonheme iron

Ferritin (4500 mol Fe/mol protein) Yes Yes (when iron is released)Hemosiderin Weakly (when iron is released) Weakly (whe iron is released)Lactoferrin (2 mol Fe3+/mol protein) No No Transferrin (2 mol Fe2+/mol protein) No No

Heme ironHemoglobin Yes (when iron is released) Yes (when iron is released) Myoglobin Yes (when iron is released) Yes (when iron is released)Cytochrome c Yes (when iron is released) Yes (when iron is released)Catalase Weakly Not observed

Products of Lipid Oxidation

Products of Lipid Oxidation

Oxidation of diene lipids

Oxidation of triene lipids

Autoxidation Photo-oxidation9-OOH D10,12,15 (37%) 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

Homolysis

Homolytic beta-scission of a carbon bond on either side of the O-containing carbon atom

Addition

C8-OOH oleate

Alkanes, Alkenes

C8-hydroperoxide of oleic acid (8-OOH oleate): 1-deceneC9-hydroperoxide of oleic acid (9-OOH oleate): 1-noneneC10-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

CH3 (CH2 )7 CH=CH-CH-(CH2 )6 -COOHO.

From C8-OOH oleateA

Aldehydes from n-6 fatty acids

Peroxidation of n-6 fatty acids (linoleic and arachidonic acid):

9-hydroperoxy linoleate: 2,4-decadienal, and 3-nonenal13-hydroperoxy linoleate: hexanal and pentanal10-hydroperoxy linoleate: 2-heptenal

Other volatile aldehydes formed: 2-hexenal, 2-octenal, 2,4- nonadienal, 4,5-hydroxydecenal, 4-hydroxy-2,3-trans- nonenal

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-nonadienal12-OOH linolenate: 2,4-heptadienal, 3-hexenal 13-OOH linolenate: 3-hexenal and 2-pentenal16-OOH linolenate: propanal

Other volatile aldehydes formed: butanal, 4,5-epoxy hepta- 2-enal, 4-hydroperoxy hexenal, 4,5-hydroxydecenal, 4- hydroxy-2,3-trans-hexenal

Malonaldehyde

Formed by further degradation of hydroperoxy aldehydesThe main precursor: monocyclic peroxides formed from

fatty acids with 3 or more double bondsIntroduces 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 acid1-PentenePentane1-Methoxy-2-methyl-1-propene2-Methyl pentane3-Methyl pentane2,2-Dimethyl pentane2,3-Dimethyl pentane3,3-Dimethyl pentane1-HexeneHexane2-Methyl hexane3-Methyl hexane3-Ethyl hexane2,4-Dimethyl hexane1-OcteneOctane2-Octene3-Octene3-Methyl octane2,6-Dimethyl octane1-HepteneHeptane2,6-Dimethyl heptane1,2,4-Trimethyl heptaneEthyl benzene1,3-Dimethyl benzene2,2,3-Trimethyl butane3-Nonen-1-olUndecanenitrileOctahydro-1H-indene1,3-Cyclopentadiene4-Methyl cyclopentene3-Methyl cyclopenteneMethyl cyclopentane1,1,3-Trimethyl cyclopentaneCyclohexaneCyclohexeneMethyl cyclohexane1,3-Dimethyl cylohexaneEthyl cyclohexane1,1,3-Trimethyl cyclohexane1,2,4-Trimethyl cyclohexane1,2,3,5-Tetramethyl cyclohexane1-Ethyl-3-methyl cyclohexanePropyl cyclohexane1-Ethyl-2,3-dimethyl cyclohexaneButyl cyclohexane1,1,2,3-Tetramethyl cyclohexane1-Methyl-4-(1-methylethyl)-cyclohexane1,1,4-Trimethyl cyclohexane1,2-Dimethyl cyclooctane