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Nur Permatasari
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A vitamin may be broadly defined as a substance that is essential for the maintenance of normal metabolic functions but which is not synthesized by the body in sufficient quantity and, therefore, must be supplied from an exogenous source
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Antioxidants
Gastro intestinal
Hepatitis Liver injury
Eye
Cataractogenesis Retinal damage
Skin
Dermatitis Age pigment
Heart
Heart attack
Teeth
Periodontis
Joints
Arthritis
Vessels
Atherosclerosis
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Brain
Trauma Stroke
Lung
Asthma
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BIOMOLECULES
activated/reactive biomolecules
ANTIOXIDANTS
membrane damage
protein damage
DNA damage
cancer
Hydroxyl radical Peroxyl radical Hydrogen peroxide Singlet oxygen Nitric oxide Peroxynitrite Hypochlorous acid
- Fenton reaction
H2O2 + Fe2+ OH + OH- + Fe3+ - is an extremely reactive oxidising radical that will react to most biomolecules
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Of the molecules that undergo autoxidation come catecholamines, haemoglobin, myoglobin, reduced cytochrome C and thiol
- Enzymatic oxidation
a term used to describe the process by which phagocytic cells consume large amounts of oxygen during phagocytosis ; between 70 and 90% of this oxygen consumption can be accounted for in farm1 11 terms of superoxide production
- Subcellular organelles Organelles such as mitochondria, chloroplasts, microsomes, peroxisomes and nuclei have been shown to generate O2* Mitochondria are the main cellular organelle for cellular oxidation reactions and the main source of reduced oxygen species in the cell.
The leaks in mitochondrial electron transport system allow O2 to accept a single electron forming O2* .
Superoxide production by the mitochondria increases in two conditions; either when the oxygen concentration is greatly increased or when the respiratory chain becomes fully reduced (as happens during ischemia). farm1 12
Iron and copper play a major role in the generation of free radicals injury and the facilitation of lipid peroxidation.
- Ischemia reperfusion injury
During ischemia two factors occur, first the production of xanthine and xanthine oxidase are greatly enhanced. Second, there is a loss of both antioxidants superoxide dismutase and glutathione peroxidase.
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Antioxidants
Enzymes Antioxidant Superoxide dismutase (SOD) Mitochondrial Cytoplasmic Extracellular Catalase Role Dismutates O2 to H2O2 Remarks Contains Manganese (Mn.SOD) Contains Copper & Zinc (CuZnSOD) Contains Copper (CuSOD)
Dismutates H2O2 to H2O Removes H2O2 and lipid peroxides Selenoproteins (contains Se2+) Primarily in the cytosol also mitochondria 16 Uses GSH
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Vitamins
Alpha tocopherol
Beta carotene
Scavenges OH, O2 and peroxy radicals Prevents oxidation of vitamin A Binds to transition metals Directly scavenges O2, OH, and H2O2 Neutralizes oxidants from stimulated neutrophils Contributes to regeneration of vitamin E
Ascorbic acid
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Vitamin E
Family of related compounds tocopherols & tocotrienols tocotrienols less widely distributed than tocopherols - considered of less nutritional importance 4 major forms based on # & position of methyl groups on ring - , , , all-rac -tocopherol
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CH 3 HO
2
H 3C CH 3 O CH 3
H 3C
H 3C
CH 3 CH 3
-Tocopherol
4'
8'
Absorption &Transport
Absorbed in the lumen intestine Tocopherol in chylomicrons equilibrates with other lipoproteins Transport in lipoproteins Uptake in chylomicron remnants by liver Secreted in VLDL from liver (via tocopherol transfer protein) site of enrichment: vs , , distributes to tissues
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Excretion
major - feces not absorbed, secreted from enterocytes, lost with enterocytes, biliary secretion
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Biochemical Function
Deficiency
in animals many symptoms species specific other compounds (e.g. Se, methionine) sometimes effective in relieving deficiency signs maintenance of membrane integrity lipid solubility -> direct protection of cell membranes
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is:
a tripeptide (-glutamyl-cysteinyl-glycine) explanation for amelioration of vitamin E deficiency by sulfur amino acids
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ROH
GSSG
NADPH
GSH Peroxidase Vitamin E PUFA (RH) Peroxidation with free radical damage ROOH (Se) GSH
Deficiency
Rare in humans Fat malabsorption disorders can lead to deficiency adults: celiac disease, pancreatitis, biliary cirrhosis genetic diseases: cystic fibrosis, others
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Deficiency - 2
Deficiency signs neuropathological changes, esp. spinal cord degeneration swollen, distrophic axons accumulation of organelles, esp. mitochondria, neurofilaments reason unknown Incr risk for athersclerosis, cancer & cataract formation? Oral administration of vit E perday,the adult RDA :10mg/day (men), 8mg/day (women)
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Deficiency - 3
Premature infants susceptible to deficiency poor status hemolytic anemia: decreased RBC survival without increased production hypothesis: low vit. E increased hemolysis due to oxidative damage results of supplementation controversial
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Toxicity
one of least toxic vitamins known at extremely high levels, vitamin E may potentiate anticoagulation effect of drugs (Coumadin) & may decr platelet adhesion pro-oxidant
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Carotenoids
About 600 identified so far Most familiar is yellow-orange pigments of carrots, -carotene Two major groups: carotenes and xanthophylls
Carotene Groups
Caroteniods
carotenes
-carotene -carotene
xanthophylls
cryptoxanthin lutein zeaxanthin
Absorption &Transport
Absorbed in the lumen intestine depend on the presence of bile acid and absorbale fat Transported via lymphatics to the liver and circulate in association with lipoprotein
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Biochemical Function
To be metabolized to retinoids (-carotene carotene , cryptoxanthine) To acts as antioxidant ( protective against light-induced skin damage in patient with porphyria) Anti cancer effects? (in vitro yes, in vivo uncertain)
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Toxicity
Megadosage treatment formation of kydney stone and rebound scurvy Pro oxidant / acts as reductant to the iron (be aggravated in disease and traumatic injury)?
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Antioxidative Nutraceuticals
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Nutraceuticals are naturally derived, bioactive compounds that have health promoting, disease preventing or medicinal properties. Nutraceuticals can be delivered in the form of food (functional foods) or as a dietary supplement or in both forms. Nutraceutical industry is a fast growing industry.
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Carcinogens
Initiation Tumor Promotion
Steroid Hormones
Sulfides, isoflavones
Prostaglandin (PGS)
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Antioxidative Nutraceuticals
Vitamin A, C, and E
Plant phenols (OH / two OH group attached to benzene ring) flavanol (epicatechin, catechin), flavanones (naringin, taxifolin), flavonols (kaempferol, quercetin), flavones/isoflavons (genistein, daidzein), anthocyanidins , phenylpropanoids (caffeic acis, p-coumaric acid) Thiol molecules Lipoic acid
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Nutraceuticals in Orange
Hesperidin
CH3O
OCH3
8 7 6
O
1
OCH3
Tangeretin
CH3O
A
5
C
4
OCH3 O
OCH3
Nobiletin
CH3O
7 6
OCH3
8
3'
OCH3
4'
O
1
1'
A
5
C
4
CH3O
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OCH3 O
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Anthocyanin
Quercetin
Beta-Carotene
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Lycopene
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Quercetin Resveratrol
Lycopene
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Hesperidin
Broccoli
Contains
Beta-Carotene
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Lycopene
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Soybean
R2
R1
OH
Isoflavone
Genistein Genistin
R1
OH OH
R2
OH O-glucose
Daidzein
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H
H
OH
O-glucose
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Daidzin
H3C
Carnosoic Acid
HOOC O OH
Carnosol
OH
O
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HO
OH
Rosemarinic Acid
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Tea
OH OH OH
HO
O OH
HO
OH
OH OH OH
OH
Epicatechin
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Epigallocatechin
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Wine
Red wine decreases coronary heart disease mortality in some part of France. Please drink up to two glasses !!! The coumaric, cinnamic, caffeic, and ferulic acids catechin, epicatechin and quercetin in are good antioxidants.
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