catalysts of lipid oxidation - iowa state universityduahn/teaching/lipid oxidation/catalysts...
TRANSCRIPT
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.
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
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%)
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 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
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