Oxidants and vitamin E

What are free radicals ?

 Free radicals are unstable molecules that are
made during normal cell metabolism ( chemical
changes that take place in a cell)
 Free radicals are substances that can act as
antioxidant
 Antioxidants helps protect cells from the
damage caused by free radicals
 Free radicals can build up in cells and can
cause damage to other molecules
 This damage may increase the risk of cancer
and other diseases
 What are antioxidants ?
 Antioxidants are molecules that prevent free
radicals from taking electrons and causing
damage to the cell
 Biological Antioxidants are Amino Acids,
Enzymes, Essential Fatty Acids, Minerals and
Vitamins
 Antioxidants are able to give an electron to
a free radical without becoming destabilized
themselves, thus stopping the free
radical chain reaction
1. During metabolism body produces waste
products with active atoms attached called “
free radicals”
2. Free radical defined as molecular species that
contains an unpaired electron in an atomic
orbital
3. The release of O2 into the environment with O-
lead to the development of toxic free radicals
as by products of oxidative metabolism
4. If unchecked, they produce degenerative
changes like aging
5. Antioxidants are “anti-aging” and reduce cell
mutations, artery damage, skin wrinkles, and
other effects of free radical damage
6. Free radical mechanisms have been
associated with a large number of disease
states including inflammation, induced injury
and ischemia
7. These radicals are unstable and highly
reactive
 Free radicals affect various important biological
molecules such as nucleic acids, lipids, and
proteins, thereby altering the normal redox
status leading to increased oxidative stress
 The free radicals induced oxidative stress has
been reported to be involved in conditions
like diabetes, neurodegenerative disorders
(Parkinson’s disease, Alzheimer’s disease and
Multiple sclerosis), cardiovascular diseases
atherosclerosis and hypertension, respiratory
diseases (asthma), cataract development,
rheumatoid arthritis and in various cancers
(colorectal, prostate, breast, lung, bladder
cancers)
Oxidative stress occurs when an oxygen
molecule splits into single atom with unpaired
electrons, which are called free radicals
 The free radicals, the reactive oxygen species
(ROS) and reactive nitrogen species (RNS), are
derived from both
a) Endogenous sources :
Mitochondria, peroxisomes, ER, phagocytic cells
b) Exogenous sources:
pollution, alcohol, tobacco smoke, heavy metals,
transition metals, industrial solvents, pesticides,
certain drugs like halothane, paracetamol, and
radiation
1) Free radicals (ROS/RNS) are produced during
metabolism and are involved in various
physiological and pathological conditions
2) When there is an imbalance between the
oxidants and antioxidants, the free radicals
accumulate leading to damage to
macromolecules such as nucleic acids,
proteins and lipids.
 Some naturally occurring antioxidants:
1 BIOFLAVONOIDS :
 Bioflavonoids are a group of naturally
occurring plant compounds
 They have unique role in protecting Vitamin C
in the body, against free radical attack
2 LINOLEIC ACID
Linoleic Acid is a polyunsaturated essential
Fatty Acid
3 LYSINE
• Lysine is an essential amino acid
• Needed for growth and to help maintain
nitrogen balance in the body, having anti–aging
properties
4 SELENIUM
 Selenium is an essential trace mineral in the
human body
 It forms an important part of antioxidant
enzymes that protects cells against the effects
of free radicals
5 PEROXIDASE (ENZYME)
 A detoxifying enzyme that eliminates
hydrogen peroxide and is one of the body’s
natural anti-oxidant enzyme
 Protects the cells against H2O2
6 SUPEROXIDE DISMUTASE
Antioxidant enzyme, which detoxifies the
superoxide anion
It is the first line of defence against free radical
damage in red blood cells
7 VITAMIN A ( BETA-CAROTENE )
• Beta-Carotene is found in plants
• Is a precursor of vitamin A
• The body converts Beta-Carotene to vitamin
A which is an antioxidant compound that can
prevent damage to DNA
8 VITAMIN C
• Antioxidant , helps with wound healing and
strengthens resistance to infection , helps in
collagen formation
R· + TOH RH + TO· vitamin E

R1 R2 R3
 CH 3 CH 3 CH 3
 CH 3 H CH 3
 H CH 3 CH 3
 H H CH 3
 Sources
 The richest dietary sources of vitamin E are
vegetable oils (primarily soy, sunflower and
corn oils), sunflower seeds and nuts
 An average daily intake of vitamin E is
 10 mg ( 15 I.U ) for men
 7.6 mg ( 11.4 I.U ) for women
 Optimal vitamin E intakes may be 100-400 I.U.
per day
 Vitamin E
1. The principal role of vitamin E is that of a free
radical scavenging antioxidant
2. Is a fat-soluble vitamin
3. Classifications of vitamin E includeds a group
of eight compounds – alpha-, beta-, gamma-
and delta-tocopherols and alpha-, beta-,
gamma- and delta tocotrienols
4. There are 2R stereoisomers of alpha-
tocopherol
5. The naturally occurring d-alpha-tocopherol has
the highest biological activity
 Functions of Vitamin E :
1. Chain-breaking antioxidant
2. Protects cell membranes
3. Enhances immune response
4. Regulates platelet aggregation
5. Inhibits PG synthesis (ref Harrisons)
6. Regulates protein kinase C activation
1. Vitamin E is the major chain-breaking
antioxidant in body tissues
2. It is the first line of defense against lipid
peroxidation, protecting cell membranes from
free radical attack
3. It protects LDLs and polyunsaturated fats in
membranes from oxidation
4. A number of antioxidants like vitamin C,
glutathione, and oxidase enzymes maintain
vitamin E in reduced state
5. Increased intake of vitamin E enhances
immune response
6. Vitamin E regulates platelet aggregation by
inhibiting platelet cyclooxygenase activity
and thus decreases prostaglandin production
7. It also has a role in regulation of protein
kinase C activation
 Absorption , Transport and Metabolism
 After absorption vitamin E is taken from
chylomicrons by the liver, and a hepatic α –
tocopherol transport protein mediates
intracellular vitamin E transport and
incorporation into very low density lipoprotein
(VLDL)
 The transport protein has particular affinity for
the RR isomeric form of α-tocopherol
 α- tocopherol having RR isomeric form is
most potent form of vitamin E
 Absorption , Transport and Metabolism (sum)
1. Absorption depends on ability of fat
2. Absorbed into lymphatic system
3. Forms a component of chylomicrons
4. Alpha-tocopherol is major tocopherol in
plasma
5. Positive association between serum lipid and
tocopherol levels
6. Normal range is 0.5-1.6 mg/dl
7. Vitamin concentrations in body tissues vary
considerably
8. Adipose tissue and adrenal glands have the
highest levels
9. Vitamin E is absorbed into the lymphatic
system from the intestine and
10. Enters the blood as a component of the
chylomicrons
11. Majority of vitamin E in plasma is in low-
density lipoproteins bound form
12. Alpha-tocopherol is the major tocopherol in
adult plasma
13. There is a positive association between
serum lipid levels and tocopherol levels
 Clinical Deficiency States :
1. Patients with malabsorption syndromes
2. Premature infants
3. Patients on TPN

 Deficiency is Characterized by :
1. Progressive neurological syndrome
2. Gait disturbances
3. Absent or altered reflexes
4. Limb weakness
5. Sensory loss in arms and legs
 Treatment :
1. Improved neurological function with
vitamin E therapy
 Newborn infants
• Newborn infants, especially those that are
premature, are susceptible to vitamin E
deficiency
• Due to inadequate body stores
• Impaired absorption
• Reduced transport capacity in the blood due
to low LDL levels at birth
Patients on TPN (Total Parenteral Nutrition)
1. Plasma vitamin E levels are frequently low in
patients on TPN
2. Major source of vitamin E in the parenteral
solution is the fat emulsion, which provides
primarily - and -tocopherols that are less
biologically active forms of tocopherol
3. So alpha-tocopherol supplementation is
required for patients on TPN
 The End
&
Thank You
Dated= 15-4-2019