Transcript antioxidants

Antioxidants & Free radicals
What are Reactive Oxygen
Species?
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ROS also known as Free oxygen radicals
Any molecule with an unpaired electron
Extremely chemically reactive
Damage cell membranes
Responsible for more than 100 human diseases
Aging, cancer, heart attacks, stroke and arthritis
Some beneficial effects
How are ROS Formed?
 Primary source is our body during energy
production
 Environmental contaminants
 Ionizing and ultraviolet radiation
 Prolonged low blood flow states
(atherosclerosis, heart attacks and stroke)
 Diet (fatty and processed foods)
 Low levels of antioxidants
Protection from ROS
Damage
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Superoxide dismutase
Catalase
Glutathion
Antioxidants in diet
Supplementation
Aging and Effect on Antioxidant
Enzymes
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Significant decline in SOD
Significant decline in catalase and glutathione
Significant decline in energy production
Cellular, tissue and system aging and failure
Scientific Support for
Antioxidants
 Animals with longer life spans have higher
antioxidant levels
 Dietary increase in antioxidants increase
life span
 Caloric restriction (reduces ROS
formation) leads to significantly increased
life span
Questions asked
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What are free radicals?
Types of free radicals
Sources of free radicals
Oxygen metabolism
 Discussion on oxidative damage and
oxidative stress
 What is antioxidant?
 Natural free radical defense systems
 What are Phytochemicals?
Food
Nutrients
Energy, building
materials
Lipid
EFA &
non-EFA
Protein
EAA &
non-EAA
Cys
Carbohydrate
Non-nutrients
Factors regulating
metabolism
Water Vitamins Minerals
C, E, b-Car
Glucose
GSH
Phytochemicals
•pigments
•Antioxidants
Zn, Se
Fibers
Other food
components
Functional food
or Neutraceuticals
Free radical-Mediated
Diseases
 Diseases of the old Chronic and degenerative diseases
(diabetes, cataracts, Alzheimer’s disease, cancers,
cardiovascular disease, and aging)
 Diseases of the young and innocent Acute and immature diseases
(Eyes: retinopathy of prematurity, Lung:
bronchopulmonary displasia, Brain: cerebral pulsy,
Pancreas: Type 1 diabetes)
What are free radicals?
 Any molecule containing one or
more unpaired electrons
Types of Free Radicals
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Reactive Oxygen Species (ROS) -
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Reactive Nitrogen Species (RNS) - NO.
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Reactive Metabolites or Intermediates
- metabolic activation of drugs, toxins,
pollutants, cigarette smokes, etc.
Reactive Oxygen Species (ROS)
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 Superoxide (O2 -)
 Hydrogen Peroxide (H2O2)
 Hydroxyl Radical (OH.) - product of
Fenton reaction catalyzed by free Fe and Cu
 Singlet Oxygen (1DgO2) - oxygen at an
excited state, requiring photosensitizers and
photons
Sources of oxygen free radicals
 In mitochondria:
- generation of energy - ATP
- glucose, fatty acids, amino acids
- O2
2H2O
4e- leakage of O2-. (superoxide)
H2O2 (hydrogen peroxide)
 In Smooth Endoplasmic Reticulum
(microsome)
- detoxification (cytochrome P-450s)
- toxins, drugs and xenobiotics
- O2 + RH
R-OH and H2O
- leakage of O2-.
- metabolic activation - X.
 In Peroxisomes
- containing oxidases for degradation of
various substrates
- glucose, amino acids, xanthine, etc.
- requires O2
- byproduct is H2O2
 In Cytoplasm
- nitric oxide (NO.) production from
Arginine
- functions as a biological messenger
- in brain, vascular endothelial cells, and
macrophages
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- NO + O2
ONOO (peroxynitrite)
NO: a Biological Messenger
 NO is a neurotransmitter (brain- bNOS)
 NO regulates blood pressure (vascular
endothelial cells- eNOS)
 NO is a cytotoxic agent (macrophagesiNOS)
 Production of Singlet Oxygen
- photosensitizers in the biological system
(bilirubin, riboflavin, retinal, porphyrin)
- requires light , O2 and photosensitizers
- chlorophyll in photosynthesis
- photodynamic therapy
Antioxidants
 Prevents the transfer of electron from O2
to organic molecules
 Stabilizes free radicals
 Terminates free radical reactions
Free Radical Defense System
 Antioxidant Enzymes
 Antioxidant Quenchers
 Antioxidant from
Foods – nutrients/nonnutrients
Antioxidant Enzymes
 Superoxide Dismutase (SOD) – to get rid
of superoxide produced from electron
transport chain, the product is hydrogen
peroxide.
 MnSOD (mitochondria).
 CuZn SOD (cytosol).
Oxygen Radical Defense
Enzymes
GSH
Peroxidase
CuZnSOD
O2•¯
H2O2
H2O + O2
Fe2+
Mn SOD
Catalase
OH•
Antioxidant Enzymes - 2
 Glutathione Peroxidase (GSH PX) – to
get rid of hydrogen peroxide (H2O2) and
some lipid peroxide. It requires reduced
glutathione (GSH) as substrate and
produces oxidized glutathione (GSSG)
as product. A cytosolic enzyme.
Functions of GSH-dependent
Enzymes
L-OH
H 2O
GSSG
GSH Px
L-OOH
H 2O 2
NADPH
GSH--Rx
GSH
NADP+
X.
GSH-TR
GSX
X-Mercapturic Acid
Glutathione
 GSH is a tripeptide, g-glutamylcysteinyl-glycine
 The sulfur atom of the cysteine
moiety is the reactive site which
provides electrons
 GSH is stable because the g bond
in glutamyl-cysteine (not the a
peptide bond) is resistant to cellular
peptidases
Glutathione
 GSH is the most abundant non-protein thiol in
mammalian cells
 GSH is a substrate for two enzymes that are
responsible for detoxification and
antioxidation.
 Other physiological roles including cysteine
storage and transport, prostaglandin
metabolism, immune function, cell
proliferation and redox balance
Glutathione Synthesis
Protein
Methionine
Cysteine
Glutamate
g-Glutamylcysteine
Glycine
Antioxidant Enzymes - 3
 Catalase –to get rid of hydrogen peroxide
produced in peroxisome.
Antioxidant Quenchers
 Cellular proteins which chelate pro-oxidant
minerals (iron and copper or others)
 Transferrin – iron transport protein
 Ferritin – iron storage protein
 Metallothionein – minerals and heavy
metals (Zn/Cu/Cd/Hg)
 Ceruloplasmin – copper transport and
storage
Antioxidants From Food
 Antioxidant nutrients – vitamin E, vitamin C,
(vitamin A?), beta-carotene
 Phytochemicals – antioxidants from plants
Discovery of Other Functions
of Phytochemicals
 Anti-oxidant
 Antiinflammatory
 Anti-estrogenic
 Anti-allergic
 Anticholesterolemic
 Anti-hemorrhagic
 Anti-mutagenic
 Anti-neoplastic