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The biochemistry of cell injury and cell death Dr Stephany Veuger.
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Transcript of The biochemistry of cell injury and cell death Dr Stephany Veuger.
The biochemistry The biochemistry of of
cell injury and cell cell injury and cell deathdeathDr Stephany VeugerDr Stephany Veuger
OverviewOverviewPart APart A Review causes of cellular damageReview causes of cellular damage Types of cellular damageTypes of cellular damage Mechanisms of cell deathMechanisms of cell death Biochemical events that lead to cell Biochemical events that lead to cell
deathdeathPart BPart B Free radicalsFree radicals Diseases associated with free radical Diseases associated with free radical
damagedamage
Learning OutcomesLearning Outcomes
Understand how the basic functions Understand how the basic functions of the cell are affected by injuryof the cell are affected by injury
Discuss morphological and Discuss morphological and biochemical changes in response to biochemical changes in response to injuryinjury
Be able to explain the types of cell Be able to explain the types of cell deathdeath
Describe the biochemical changes in Describe the biochemical changes in response to ischaemiaresponse to ischaemia
Causes of cell injuryCauses of cell injury
PhysicalPhysical Chemical Chemical InfectiousInfectious ImmunologicImmunologic Genetic derangementGenetic derangement Nutritional and Oxygen ImbalancesNutritional and Oxygen Imbalances Metabolic changes Metabolic changes
Cellular damageCellular damage
SUBLETHALSUBLETHAL Damage is minimalDamage is minimal Recovery Recovery
LETHALLETHAL Continued damage Continued damage Damage is massive Damage is massive
Mechanisms of cell Mechanisms of cell injuryinjury
Injurious agents can affect the cell at Injurious agents can affect the cell at a number of levels by damaging :a number of levels by damaging :
Plasma membranePlasma membrane Aerobic respiration and ATP Aerobic respiration and ATP
productionproduction Protein synthesisProtein synthesis Genetic machineryGenetic machinery
Morphological indicators of Morphological indicators of
cell injurycell injury Alterations to plasma membrane Alterations to plasma membrane Cytoskeleton damageCytoskeleton damage Mitochondrial condensationMitochondrial condensation Mitochondrial swellingMitochondrial swelling Dilatation of ERDilatation of ER Ribosome detachmentRibosome detachment Alterations to lysosomesAlterations to lysosomes
Morphological changes Morphological changes following sub-lethal injuryfollowing sub-lethal injury
Mitochondrial swelling (low amplitude Mitochondrial swelling (low amplitude swelling) swelling)
-vacuoles distort cristae-vacuoles distort cristae
-reversible-reversible ER swellingER swelling
-loss of ribosomes-loss of ribosomes High amplitude swellingHigh amplitude swelling
-cristae destroyed-cristae destroyed
--irreversibleirreversible
ATP-dependent ATP-dependent processes affectedprocesses affected
Morphological changes Morphological changes following sub-lethal injuryfollowing sub-lethal injury
Under the microscope, these changes are seen Under the microscope, these changes are seen as;as;
Cellular swellingCellular swelling Pale cytoplasmPale cytoplasm Small intracellular vacuolesSmall intracellular vacuolesCLOUDY SWELLING or HYDROPIC CLOUDY SWELLING or HYDROPIC
DEGENERATIONDEGENERATION
Accumulation of lipidAccumulation of lipidFATTY CHANGEFATTY CHANGE
Fatty ChangeFatty Change
Deficiency in lipid acceptor proteins, Deficiency in lipid acceptor proteins, preventing export of formed triglyceridespreventing export of formed triglycerides-carbon tetrachloride, malnutrition, hypoxis-carbon tetrachloride, malnutrition, hypoxis
Increased mobilisation of free FA into cells Increased mobilisation of free FA into cells - diabetes mellitus and nutritional deprivation- diabetes mellitus and nutritional deprivation
Increased conversion of fatty acids to Increased conversion of fatty acids to triglyceridestriglycerides-alcohol abuse-alcohol abuse
Reduced oxidation of triglycerides to acetyl-Reduced oxidation of triglycerides to acetyl-coAcoA-hypoxia, toxins-hypoxia, toxins
Cell survivalCell survival- Following injury, major cellular Following injury, major cellular
components need to be maintained to components need to be maintained to promote survival ;promote survival ;
Cell membranesCell membranes MitochondriaMitochondria CytoskeletonCytoskeleton Cellular DNACellular DNA
- These systems are not interdependent - These systems are not interdependent - Threshold – death - Threshold – death
Plasma membranePlasma membrane
Integrity following injury is Integrity following injury is ESSENTIALESSENTIAL
Direct Direct Failure of phospholipid biosynthesisFailure of phospholipid biosynthesis Particularly vulnerable to free Particularly vulnerable to free
radical attackradical attack Degradation of phospholipids by Degradation of phospholipids by
Ca2+ dependent phospholipasesCa2+ dependent phospholipases
Morphological changes Morphological changes following lethal injury following lethal injury
High amplitude swellingHigh amplitude swelling
Morphological changes to the nucleusMorphological changes to the nucleus
Appearance of membrane blebs and holesAppearance of membrane blebs and holes
Dissolution of the nucleusDissolution of the nucleus
Distinct structural changes to cell leading to Distinct structural changes to cell leading to dissolution of cell via release of lysosomal enzymesdissolution of cell via release of lysosomal enzymes
AUTOLYSISAUTOLYSIS
Morphological changes Morphological changes following lethal injury following lethal injury
(nucleus)(nucleus) PYKNOSISPYKNOSIS
-condensation of nuclear chromatin-condensation of nuclear chromatin Loss of nucleolusLoss of nucleolus KARRYORRHEXISKARRYORRHEXIS
-fragmentation of the nucleus-fragmentation of the nucleus KARYOLYSISKARYOLYSIS
-complete dissolution of nuclear -complete dissolution of nuclear materialmaterial
Summary ISummary I Cell have limited capacity to adapt to change Cell have limited capacity to adapt to change
Mild injury can be accommodated by cells but Mild injury can be accommodated by cells but is evident by biochemical and morphological is evident by biochemical and morphological changeschanges
Sub-lethal –reversible Sub-lethal –reversible Injury that is sufficient to cause morpholgical Injury that is sufficient to cause morpholgical
changes to the nucleus is usually lethalchanges to the nucleus is usually lethal Dissolution of nuclear and cytoplasmic contents Dissolution of nuclear and cytoplasmic contents
is caused by the release of lysosomal enzymesis caused by the release of lysosomal enzymes
Cell deathCell death
-Follows irreversible cell damage-Follows irreversible cell damage
-Can be by accident or design-Can be by accident or design
ApoptosisApoptosis NecrosisNecrosis
Different morphological changes Different morphological changes
ApoptosisApoptosis
Routine – repair and cell cycle (p53)Routine – repair and cell cycle (p53)
Programmed – co-ordinated- Programmed – co-ordinated- “shrinkage”“shrinkage”
Stimuli mediated by immune system ; Stimuli mediated by immune system ; cytokinescytokines
Autophagy (self digestion)Autophagy (self digestion)
NecrosisNecrosis
Massive damage to cellular systems Massive damage to cellular systems
Uncontrolled loss of large numbers of Uncontrolled loss of large numbers of cellscells
Extensive organelle and cell “swelling”Extensive organelle and cell “swelling”
Rupture of plasma membrane and Rupture of plasma membrane and dissolution of the celldissolution of the cell
Biochemical determinants Biochemical determinants of necrotic changeof necrotic change
ATP ATP Calcium homeostasisCalcium homeostasis pHpH Reactive Oxygen Species (ROS)Reactive Oxygen Species (ROS) Intracellular antioxidant levelsIntracellular antioxidant levels
ATPATP
Produced by cellular respirationProduced by cellular respiration biosynthesisbiosynthesis Critical for function of many Critical for function of many
transport pumpstransport pumps Critical for cell signalling processesCritical for cell signalling processes Cloudy swelling and fatty change Cloudy swelling and fatty change
CalciumCalcium Normal concentration in cytosol very lowNormal concentration in cytosol very low
-rapidly removed by ATP-dependent pumps-rapidly removed by ATP-dependent pumps
-bound to buffering proteins (calbindin, -bound to buffering proteins (calbindin, parvalbumin)parvalbumin)
Increased intracellular calcium brought about Increased intracellular calcium brought about by;by;
-↑permeability of Ca2+ channel-↑permeability of Ca2+ channel
-direct membrane damage-direct membrane damage
-ATP depletion-ATP depletion
-mitochondrial damage-mitochondrial damage
Cytosolic free calcium is a Cytosolic free calcium is a potent destructive agentpotent destructive agent
CALCIUM STORESMitochondria
ER lumenPumped to extracellular
spaceBound to binding proteins
Released following cell injury
FREE Ca 2+
Activation of ATPases
Activation ofphospholipases
Activation ofproteases
Membranedamage
Destabilising of cytoskeleton
Reduced ATP
Reative Oxygen species Reative Oxygen species (ROS)(ROS)
Most important free radicals in the Most important free radicals in the body are the oxygen-derived free body are the oxygen-derived free radicalsradicals
Attack bio-moleculesAttack bio-molecules
Lipid peroxidation - decreases Lipid peroxidation - decreases membrane fluidity and destabilises membrane fluidity and destabilises membrane receptors.membrane receptors.
Changes in metabolismChanges in metabolism
Accumulation of materials as a Accumulation of materials as a result of changes in metabolism may result of changes in metabolism may compromise normal function of cellcompromise normal function of cell
Lipid (fatty change already covered)Lipid (fatty change already covered) Protein –kidneys, reversibleProtein –kidneys, reversible Carbohydrate-diabetes, glycogen Carbohydrate-diabetes, glycogen
storage disordersstorage disorders pigmentspigments
ISCHAEMIAISCHAEMIA
Excellent example of the cellular Excellent example of the cellular response to a damaging stimulusresponse to a damaging stimulus
ISCHAEMIA = LACK OF OXYGEN ISCHAEMIA = LACK OF OXYGEN SUPPLYSUPPLY
HYPOXIA =LACK OF OXYGENHYPOXIA =LACK OF OXYGEN
DefinitionsDefinitions
HYPOXIAHYPOXIA
-decrease in oxygen in arterial blood or -decrease in oxygen in arterial blood or tissuestissues
ISCHAEMIAISCHAEMIA
-local anaemia, leading to hypoxia eg. -local anaemia, leading to hypoxia eg. Obstruction to blood flow to organ/tissueObstruction to blood flow to organ/tissue
INFARCTIONINFARCTION
-sudden insufficiency of blood supply -sudden insufficiency of blood supply producing macroscopic areas of necrosis producing macroscopic areas of necrosis (eg. MI)(eg. MI)
Biochemical and Biochemical and morphological changes due morphological changes due
to Ischaemia (I)to Ischaemia (I) Shift from aerobic to anaerobic respirationShift from aerobic to anaerobic respiration Reduction in ATPReduction in ATP Failure of ATP-dependent pumps (Na+/K+, Failure of ATP-dependent pumps (Na+/K+,
ATPase and Ca2+)ATPase and Ca2+) Failure to maintain intracellular ionic Failure to maintain intracellular ionic
balancebalance Accumulation of Na+ in cytoplasmAccumulation of Na+ in cytoplasm Ingress of calcium and water and outflow Ingress of calcium and water and outflow
of potassium ionsof potassium ions
Cloudy Swelling and disruption of Cloudy Swelling and disruption of internal membrane systemsinternal membrane systems
Biochemical and Biochemical and morphological changes due morphological changes due
to Ischaemia (II)to Ischaemia (II)Integrity of RER relies on Na+ pumpIntegrity of RER relies on Na+ pump
ribosomes detachribosomes detach Protein synthesis ceasesProtein synthesis ceases Calcium – activation of several Calcium – activation of several
destructive enzyme systems destructive enzyme systems Phospholipid synthesis ceasesPhospholipid synthesis ceases
Further disruption of membranesFurther disruption of membranes
Biochemical and Biochemical and morphological changes due morphological changes due
to Ischaemia; pH (III)to Ischaemia; pH (III) Anaerobic respiration results in Anaerobic respiration results in
lactic acid productionlactic acid production Intracellular pH decreasesIntracellular pH decreases Membranes under acid attackMembranes under acid attack pH further augmented via phosphate pH further augmented via phosphate
ions produced by Ca2+ activated ions produced by Ca2+ activated phosphatasesphosphatases
Fall in pH stimulates pyknosisFall in pH stimulates pyknosis
Biochemical and Biochemical and morphological changes due morphological changes due
to Ischaemia; pH (IV)to Ischaemia; pH (IV) LysosomesLysosomes Release of destructive enzymes leads to Release of destructive enzymes leads to
karryhrrexis and karyolyisskarryhrrexis and karyolyiss Cell deathCell death Neighbouring cells injuredNeighbouring cells injured
Initial changes in ischaemia reversible Initial changes in ischaemia reversible but nuclear changes catastrophic for but nuclear changes catastrophic for cellcell
ISCHAEMIAISCHAEMIA
Reduced oxidative phosphorylation
Anaerobic respiration
Potassium
Water
Calcium
?ATPDecrease in sodium pump
Lactic acid
?lysosomes
Cell death
? pHribosomes detach
? Protein synthesis
??
?
ISCHAEMIAISCHAEMIA
Reduced oxidative phosphorylation
Anaerobic respiration
Potassium
Water
Calcium
?ATPDecrease in sodium pump
Lactic acid
?lysosomes
Cell death
? pHribosomes detach
? Protein synthesis
??
?
ISCHAEMIAISCHAEMIA
Reduced oxidative phosphorylation
Anaerobic respiration
Potassium
Water
Calcium
ATPDecrease in sodium pump
Lactic acid
lysosomes
Cell death
pHribosomes detach
Protein synthesis
pyknosis
karyorrhexis
karyolysis
Summary IISummary II
Cells die by two main pathwaysCells die by two main pathways
Biochemical determinants of injury Biochemical determinants of injury and death ATP, Ca2+, pH, ROS and death ATP, Ca2+, pH, ROS
Ischaemia most common injury in Ischaemia most common injury in clinical medicineclinical medicine
OverviewOverview
What are free radicals?What are free radicals? Sources of free radicalsSources of free radicals Types of free radicals (ROS)Types of free radicals (ROS) Types of free radical damageTypes of free radical damage Diseases associated with free Diseases associated with free
radicalsradicals Anti-oxidant mechanismsAnti-oxidant mechanisms
Learning OutcomesLearning Outcomes
Define the terms free radical and reactive Define the terms free radical and reactive oxygen speciesoxygen species
Characterise the major reactive oxygen Characterise the major reactive oxygen species and their sourcesspecies and their sources
Discuss the negative effects of ROS on bio-Discuss the negative effects of ROS on bio-molecules molecules
Describe the cellular defence mechanisms Describe the cellular defence mechanisms against free radicalsagainst free radicals
What is a free radical?What is a free radical?
A radical is an atom or molecule A radical is an atom or molecule with one or more unpaired electronswith one or more unpaired electrons
A radical that can move freely within A radical that can move freely within cell and across membranes is a free cell and across membranes is a free radicalradical
Highly unstable and extremely Highly unstable and extremely reactivereactive
Free radicalsFree radicals
Most molecules found in the body Most molecules found in the body are not radicals. are not radicals.
Any reactive FR generated will often Any reactive FR generated will often react with such non-radicals i.e. react with such non-radicals i.e. sugars, amino acids, phospholipids, sugars, amino acids, phospholipids, nucleotides, polysaccharides, nucleotides, polysaccharides, proteins, nucleic acids etc.proteins, nucleic acids etc.
When this happens, a When this happens, a free radical free radical chain reactionchain reaction resultsresults
Sources of free radicalsSources of free radicals
Ionising radiationIonising radiation Chemicals Chemicals Exposure to excess oxygenExposure to excess oxygen
Cell respirationCell respiration InflammationInflammation
GB.UNN.10GB.UNN.10
Reactive oxygen species (ROS)
OO22-•-•
HH22OO22
OHOH••
RORO••
RCOORCOO••
HOClHOCl
SuperoxideSuperoxide leakage from the electron transport leakage from the electron transport chain is the main sourcechain is the main source
Hydrogen Hydrogen peroxideperoxide
Not a free radical itself, but is Not a free radical itself, but is dangerous because in the presence of dangerous because in the presence of a transition metal it quickly produces a transition metal it quickly produces OHOH••
Hydroxyl Hydroxyl radicalradical
Generated from HGenerated from H22OO2 2 by Fenton by Fenton reactionreaction
Organic radicalOrganic radical Usually produced from C=C bondsUsually produced from C=C bonds
Peroxyl radicalPeroxyl radical Generated when radicals attack lipidsGenerated when radicals attack lipids
Hypochlorous Hypochlorous acidacid
Generated on purpose as part of Generated on purpose as part of immune “respiratory burst”immune “respiratory burst”
AbstractionAbstraction
Stripping of electrons from other atoms Stripping of electrons from other atoms or moleculesor molecules
R• + HB RH + B•
Propogation
H abstraction on sugars such as deoxyribose yields many products, some of which are mutagenic.
H abstraction on unsaturated membrane lipids is one of the most important aspects of damage to cells by FRs.
AdditionAddition
Attack of hydroxyl radical on DNA Attack of hydroxyl radical on DNA bases bases
Thymine + OH● Thymine + OH● Thymine-OH●Hydroxythymine radical
Thymine-OH● + OH● Thymine glycol
Effect on lipidEffect on lipid Peroxidation of membrane lipids is the Peroxidation of membrane lipids is the
most important cause of serious acute most important cause of serious acute damage to cells damage to cells Malondialdehyde = marker for oxidative Malondialdehyde = marker for oxidative
stressstress
chain reaction of lipid peroxidationchain reaction of lipid peroxidation- H abstraction from a polyunsaturated H abstraction from a polyunsaturated
fatty acid in a membrane or lipoproteinfatty acid in a membrane or lipoprotein- Introduction of a polar group –OOH Introduction of a polar group –OOH
into hydrophobic regioninto hydrophobic region- Attack of one reactive FR can oxidise Attack of one reactive FR can oxidise
multiple fatty acid side chains to multiple fatty acid side chains to lipid lipid peroxidesperoxides
Effect on DNAEffect on DNA
Reactive FRs such as the hydroxyl radical Reactive FRs such as the hydroxyl radical can react with both the deoxyribose and can react with both the deoxyribose and the bases of DNAthe bases of DNA
TheThe sugar component will be affected by sugar component will be affected by H abstractionH abstraction, resulting in many , resulting in many products, many of which are products, many of which are mutagenicmutagenic..
Bases can be affected by Bases can be affected by additionaddition reactions, ultimately leading to reactions, ultimately leading to mutationmutation and and cellularcellular derangementderangement
Depletion of NADH poolsDepletion of NADH pools
Effect on proteinsEffect on proteins
Formation of disulphide bridges by Formation of disulphide bridges by oxidation of the thiol groups (-SH) of oxidation of the thiol groups (-SH) of cysteine residuescysteine residues
Attack metal binding sites leading to Attack metal binding sites leading to degradation by proteasesdegradation by proteases
Loss of biological activity eg enzymesLoss of biological activity eg enzymes Malondialdehyde - protein adducts or Malondialdehyde - protein adducts or
advanced lipoxidation end products advanced lipoxidation end products (APE)(APE)
Effect on carbohydratesEffect on carbohydrates
Hydroxyl radical - H abstractionHydroxyl radical - H abstraction
Depolymerisation of hyaluronic acid Depolymerisation of hyaluronic acid -Synovial fluid viscosity-Synovial fluid viscosity
ROS as a protective ROS as a protective mechanismmechanism
Peroxisome has highest concentration of Peroxisome has highest concentration of FRsFRs
Phagocytes use the generation of FRs in Phagocytes use the generation of FRs in phagosome to attack and destroy bacteriaphagosome to attack and destroy bacteria
RESPIRATORY BURST –rapid use of RESPIRATORY BURST –rapid use of oxygen to generate FRsoxygen to generate FRs
Problem during e.g. MI. Designed to Problem during e.g. MI. Designed to remove dead cells but causes local remove dead cells but causes local inflammationinflammation
The superoxide radicalThe superoxide radicalO2●-O2●-
Generated during electron transport Generated during electron transport chain chain
Oxidase enzymesOxidase enzymes
O2 O2●-O2 O2●-oxidase
The hydroxyl radicalThe hydroxyl radical OH● OH●
An extremely reactive species An extremely reactive species Reacts with great speed with Reacts with great speed with
whatever molecules are in its whatever molecules are in its vicinityvicinity
Responsible for many of the effects Responsible for many of the effects of high level radiation in the human of high level radiation in the human bodybody
Can be formed by fenton reaction Can be formed by fenton reaction
Promoters of free radical Promoters of free radical damage : Metal ionsdamage : Metal ions
Iron and copper Iron and copper Encourage formation of hydroxyl radicalEncourage formation of hydroxyl radical
FeFe2+2+ + H + H22O O
Iron conjugated to protein and stored as Iron conjugated to protein and stored as ferritin/ transported as transferrinferritin/ transported as transferrin
Copper is transported as caeruloplasminCopper is transported as caeruloplasmin
Free ions = Free ions = pro-oxidantspro-oxidants
Fe3+ + OH● + OH
Free Radicals and Free Radicals and diseasedisease
Accumulation of damaged proteins, Accumulation of damaged proteins, carbohydrates, lipids andcarbohydrates, lipids and
nucleic acids contributes to a wide range of nucleic acids contributes to a wide range of human diseaseshuman diseases
FR damage Cell injury
Apoptosis Necrosis Ageing CancersAthero-sclerosis
Degenerativediseases
Cell death
FRs and cardiovascular FRs and cardiovascular diseasedisease
There is growing evidence that lipid There is growing evidence that lipid peroxidation occurs in blood vessel peroxidation occurs in blood vessel wallswalls
Contributes to the development of Contributes to the development of atherosclerosisatherosclerosis raising the risk of raising the risk of stroke and myocardial infarction.stroke and myocardial infarction.
LipofushinLipofushin
Free radicals in cancerFree radicals in cancer
FRs can severely damage DNA of FRs can severely damage DNA of cells which can lead to abnormal cells which can lead to abnormal cells & cancer growth cells & cancer growth
FRs can convert certain chemicals FRs can convert certain chemicals into carcinogensinto carcinogens
DNA repair / apoptois DNA repair / apoptois
-Hydroxyguanine -Hydroxyguanine
Summary ISummary IFree radicalsFree radicals
Extremely reactive chemical species with an unpaired electronExtremely reactive chemical species with an unpaired electron
Produced in cells as metabolic by-productsProduced in cells as metabolic by-products
Produced by phagocytic cells as part of inflammatory defencesProduced by phagocytic cells as part of inflammatory defences
Produced by the action of toxic compoundsProduced by the action of toxic compounds
Cause cell injuryCause cell injury
Caused by cell injuryCaused by cell injury
Summary IISummary IIFree radicalsFree radicals
Free radicals can cause oxidative damage Free radicals can cause oxidative damage to cells componentsto cells components
The most dangerous free radical is the The most dangerous free radical is the hydroxyl ionhydroxyl ion
Damage by free radicals is believed to Damage by free radicals is believed to contribute to the pathogenesis of many contribute to the pathogenesis of many chronic diseaseschronic diseases
AntioxidantsAntioxidants
Defence systems Defence systems
1) Directly – blocking formation or 1) Directly – blocking formation or scavengingscavenging
2) Binding metals that catalyse ROS 2) Binding metals that catalyse ROS formationformation
3) Enzyme activity 3) Enzyme activity
Intracellular Intracellular antioxidantsantioxidants
Glutathione Glutathione peroxidaseperoxidase
Removes hydrogen Removes hydrogen peroxideperoxide
Selenium dependentSelenium dependent
Cytosol and Cytosol and mitochondriamitochondria
GlutathioneGlutathione Scavenger of hydroxyl Scavenger of hydroxyl radicalradical
Superoxide Superoxide dismutasedismutase
Catalyses conversion of Catalyses conversion of superoxide to hydrogen superoxide to hydrogen peroxideperoxide
CatalaseCatalase Removes hydrogen Removes hydrogen peroxideperoxide
Dietary antioxidantsDietary antioxidants
Vitamin E (Vitamin E (αα--tocopherol)tocopherol)
Inhibits lipid Inhibits lipid peroxidationperoxidation
Vitamin C (ascorbic Vitamin C (ascorbic acid)acid)
Inhibits pro-oxidantsInhibits pro-oxidants
Vitamin A (Vitamin A (ββ--carotene)carotene)
Lipid soluble radical Lipid soluble radical scavengerscavenger
ZincZinc Component of Component of superoxide dismutasesuperoxide dismutase
ManganeseManganese Component of Component of superoxide dismutasesuperoxide dismutase
Copper Copper Component of Component of superoxide dismutasesuperoxide dismutase
SeleniumSelenium Component of Component of glutathione peroxidaseglutathione peroxidase
Antioxidant enzymesAntioxidant enzymes
Superoxide dismutase converts superoxide Superoxide dismutase converts superoxide to hydrogen peroxide and oxygento hydrogen peroxide and oxygen
OO22●- + O●- + O22●- + 2H ●- + 2H
catalase and glutathione peroxidase convert catalase and glutathione peroxidase convert hydrogen peroxide to water and oxygen hydrogen peroxide to water and oxygen
2H2H22OO22
H2O2 + O2
O2 + H2O
Summary IIISummary IIIAntioxidantsAntioxidants
Maintenance of cell integrity Maintenance of cell integrity depends on a balance between FR depends on a balance between FR activity and antioxidant statusactivity and antioxidant status
Fat-soluble antioxidant vitamins are Fat-soluble antioxidant vitamins are essential for controlling lipid essential for controlling lipid peroxidationperoxidation
Diet rich in fruit and vege may Diet rich in fruit and vege may prevent diseaseprevent disease