This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Structuresfarm1
*
Degenerative Diseases
cell growth & maintenance
membrane damage
protein damage
Lipid peroxidation
Cell membranes are a rich resource of PUFA, which are readily
attacked by oxidising agents; a process that is called lipid
peroxidation disruption of hydrophobic nature of membranes
fragmentation and loss of membrane-bound enzymatic activities
Protein damage
Proteins & nucleic acids seem to be less susceptible than PUFAs
to free radicals affect enzyme, receptor
DNA damage
*
Reactive Oxygen Species
Superoxide (O2·*)
- formed when oxygen is reduced by the transfer of a single
electron to its outer shells
- the major source of superoxide in-vivo is the electron leakage
that results from the electron transfer chain of the
mitochondria
*
2O2·*+ 2H* H2O2 + O2
not a free radical but falls in the category of reactive oxygen
species.
*
- Fenton reaction
H2O2 + Fe2+ ·OH + OH- + Fe3+
*
Enzymatic oxidation
Respiratory burst
*
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·* .
*
Transition metals ions
Iron and copper play a major role in the generation of free
radicals injury and the facilitation of lipid peroxidation.
Ischemia reperfusion injury
*
2. Minimize the avaibility of pro oxidant ( transferin, metal
chelation)
3. Protect biomolecules against ROS (heat shock
protein)
4. Low-molecular-mass agents that scavenge ROS (gluthatione,
uric acid,bilirubin ,vitamin)
*
Dismutates O2· to H2O2
Catalase
Removes H2O2 and lipid peroxides
*
Breaks lipid peroxidation Lipid peroxide and O2· and ·OH
scavenger
Fat soluble vitamin
Beta carotene
Scavenges ·OH, O2· and peroxy radicals Prevents oxidation of
vitamin A Binds to transition metals
Fat soluble vitamin
Directly scavenges O2·, ·OH, and H2O2 Neutralizes oxidants from
stimulated neutrophils Contributes to regeneration of vitamin
E
Water soluble vitamin
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
H
O
C
H
3
C
H
3
O
C
H
3
H
3
C
H
H
H
3
C
H
3
C
C
H
3
C
H
3
Tocopherol in chylomicrons equilibrates with other
lipoproteins
Transport in lipoproteins
Secreted in VLDL from liver (via tocopherol transfer protein)
site of enrichment: vs , ,
other mechanisims?
*
*
species specific
maintenance of membrane integrity
*
Selenium is part of glutathione peroxidase
metabolizes lipid hydroperoxides
Glutathione is:
a tripeptide (g-glutamyl-cysteinyl-glycine)
*
adults: celiac disease, pancreatitis, biliary cirrhosis
genetic diseases: cystic fibrosis, others
*
swollen, distrophic axons
reason unknown
Incr risk for athersclerosis, cancer & cataract
formation?
*
poor status
hypothesis: low vit. E increased hemolysis due to oxidative
damage
results of supplementation controversial
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
Most familiar is yellow-orange pigments of carrots, -carotene
Two major groups: carotenes and xanthophylls
*
Absorption &Transport
Absorbed in the lumen intestine depend on the presence of bile acid
and absorbale fat
*
To be metabolized to retinoids (-carotene Β-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)
*
Biochemical function: cofactor for at least eight enzymes
At the tissue level, a major function collagen synthesis ( vit C
deficiency can lead scurvy)
The antioxidant properties protect NO, protect against age-related
cataract
*
Absorption & Excretion
Absorbed in the lumen intestine via an energy dependent process
(saturable)
The daily intake > 100mg excreted, in adult RDA: 60
mg/daily
*
Megadosage treatment formation of kydney stone and rebound
scurvy
*
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.
*
Initiation
Tumor
Promotion
Tumor
Promotion
Tumor
Promotion
Tumor
Promotion
Oxidative
Damage
Carcinogens
Steroid
Hormones
Prostaglandin
(PGS)
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
Chelation of metals
*
Hesperidin
Beta-Carotene
Lycopene
farm1
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.
3.psd
O
O
C
H
3
O
C
H
3
O
O
C
H
3
O
C
H
3
1
O
C
H
3
5
6
7
8
1