antioxidants.ppt

What are Reactive Oxygen
Species?
 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
 Superoxide dismutase
 Catalase
 Glutathion
 Antioxidants in diet
 Supplementation

Aging and Effect on Antioxidant
Enzymes
 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
 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?

Nutrients Non-nutrients
Energy, building
materials
Factors regulating
metabolism
Lipid Protein Carbo-
hydrate
Vitamins Minerals
EFA &
non-EFA Glucose
Water
Phyto-
chemicals
•pigments
•Antioxidants
Fibers
Other food
components
Food
GSH
Cys
Functional food
or Neutraceuticals
C, E, b-Car
Zn, Se
EAA &
non-EAA

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
 Reactive Oxygen Species (ROS) -
 Reactive Nitrogen Species (RNS) - NO.
 Reactive Metabolites or Intermediates
- metabolic activation of drugs, toxins,
pollutants, cigarette smokes, etc.

Reactive Oxygen Species (ROS)
 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
- 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 (macrophages-
iNOS)

 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/non-
nutrients

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
O2•¯ H2O2 H2O + O2
Mn SOD Catalase
GSH
Peroxidase
CuZnSOD
OH•
Fe2+

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
H2O GSSG NADPH
L-OOH
H2O2
GSH NADP+
X.
GSX
X-Mercapturic Acid
GSH Px
GSH-TR
GSH--Rx

Glutathione
 GSH is a tripeptide, g-glutamyl-
cysteinyl-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

antioxidants.ppt

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