What are Vitamins?

 Organic compounds occurring in small quantities in different natural foods

 Necessary for growth and maintenance of good health in human beings and animals
 Vitamins are essential food factors, which are required for the proper utilization of the proximate
principles of food like carbohydrates, lipids and proteins.

History of Vitamins:
 Discovery of vitamins started from observation of deficiency manifestations, e.g. scurvy, rickets,
beriberi, etc.
 "Vitamine" from "vital" + "amine" "e' was dropped because of lack of amino groups

FREDERICK GOWLAND HOPKINS

 The Vitamin Theory was suggested by Hopkins in 1912 (Nobel Prize, 1929).

GENERAL CHARACTERISTICS & FUNCTIONS OF VITAMINS

1. Vitamins are not synthesized by the body and must come from food
 Except for Vitamin D which can be absorbed from sunlight by our skin
 Other vitamins can be manufactured in small quantities by our own microbiota or intestinal flora

2. Vitamins are vital, organic, dietary substance that is necessary in only very small amounts
 For metabolic functions or to prevent certain deficiencies.

3. Few are single substances; most are families of chemically related substances sharing biological
activities.
 Classified according to their physical properties.

4. Some vitamins are fat soluble; the others are water soluble
 Fat-soluble vitamins (A, D, E, and K) have predominantly aromatic and aliphatic character
 Fat-soluble vitamins (B1, B2, B3, B5, B6, B7, B9, B12, C) have one or more polar or lonizable
groups

5. Vitamins function as antioxidants, affectors of gene transcription, H+/e donors/acceptors, hormones, and
coenzymes

What are Fat Soluble Vitamins?

 Fat-soluble vitamins are vitamins A, D, E, and K. They are present in foods containing fats. The body
absorbs these vitamins as it does dietary fats. They do not dissolve in water.

VITAMIN A
 Vitamin A and carotene can be obtained from either animal or vegetable sources. The animal form is
divided between retinol and dehydroretinol whereas the vegetable carotene can be split into four very
potent groups- alpha- carotene, beta-carotene, gamma carotene and crypto-carotene.
 Fat Soluble: Vision. Reproduction, Bone Health, Immune System, Skin

CHEMISTRY:
 The retinal may be reduced to retinol by retinal reductase
 Retinol -vitamin A
 Alcohol Retinal - vitamin A
 aldehyde Retinoic acid - vitamin A acid
  The side chain contains alternate double bonds, and hence many isomers are possible. The all trans
variety of retinal, Vitamin Al is most common. Vitamin A2 is found in fish oils and has an extra double
bond in the ring. Biologically important compound is 11-cis-retinal

TRANSPORT FROM LIVER TO TISSUES:

 The retinol binding protein, or RBP, transports vitamin A form the liver to peripheral tissues as trans-
retinol. One molecule of RBP binds one molecule of retinol.

DIGESTION AND ABSORPTION:

 Di-oxygenase cleaves Beta carotene to form retinal.
 NADH or NADPH dependent retinal reductase present in the intestinal mucosa reduces retinal into
retinol.
 Intestine- major site of absorption.
 In biliary tract obstruction and steatorrhoea, vitamin A absorption is reduced.
 Mucosal cell- the retinol is re-esterified with fatty acids, incorporated into chylomicrons and transported
to liver. Liver stellate cells- vitamin is stored as retinol palmitate.

UPTAKE BY TISSUES:
 Specific receptors on the retina, skin, gonads, and other tissues bind to the retinol-RBP complex. The
RBP is not able to enter the cell. Vitamin attaches to cellular retinoic acid binding protein (CRBP) and
then to hormone responsive elements (HRE) of DNA in the cytoplasm of cells. Genes are therefore
activated.

BIOCHEMICAL ROLE OF VITAMIN A

1. WALD'S VISUAL CYCLE
A. Generation of Nerve impulse
 Rhodopsin plays the pivotal role in vision. It is a membrane protein found in the photoreceptor cells of
the retina. Rhodopsin is made up of the protein and 11-cis retinal
 When light falls on the retina, the 11-cis-retinal isomerizes to all-trans-retinal
 The unstable intermediates produced are: Rhodopsin -Batho rhodopsin Lumirhodopsin -Metarhodopsin-
I→ Metarhodopsin-II → and finally Opsin + all-trans-retinal.
 Blue color represent reactions in photoreceptor matrix. Green background represents reactions in retinal
pigment epithelium. Red depicts blood. Yellow shows reactions in liver
 Visual pigments are G-protein coupled receptors and 11-cis-retinal locks the receptor protein (opsin) in
its inactive form
 Transducin is the G protein in retina

B. Regeneration of 11-cis- retinal

 Opsin remains in retina; but trans retinal enters the blood circulation. Later cis-retinal is generated,
reaches retina. The re attachment of 11-cis retinal to opsin is critical for shutting off the pigment's
catalytic activity.
 The all-trans-retinal is isomerized to 11 cis-retinal in the retina itself in the dark by the enzyme retinal
isomerase. This reaction is taking place in retinal pigment epithelium. The 11-cis retinal can recombine
with opsin to regenerate rhodopsin.

2. DARK ADAPTATION MECHANISM

 Bright light depletes stores of rhodopsin in rods. Therefore, when a person shifts suddenly from bright
light to a dimly lit area, there is difficulty in seeing
 It is increased in vitamin A deficiency. Red light bleaches rhodopsin to a lesser extent
 Torsten Wiesel
3. RODS ARE FOR VISION IN DIM LIGHT

4. CONES ARE FOR COLOR VISION

 Reduction in number of cones or the cone proteins, will lead to color blindness. One eye contains about
6 million cones
DID YOU KNOW:
 Colors have Profound Influence in Life

3 types of cones:
 blue (cyanopsin), green (iodopsin) or red (porphyropsin).

5. OTHER BIOCHEMICAL FUNCTIONS OF VITAMIN A

 Retinoic acid has a role in the regulation of gene expression and differentiation of tissues
 Retinol is necessary for the reproductive system
 Anti-oxidant property
 Beta carotenes may be useful in preventing heart attacks
 Vitamin A is necessary for the maintenance of normal epithelium and skin.

Deficiency Manifestations of Vitamin A

1. Night Blindness or Nyctalopia
2. Xerophthalmia
3. Bitot's Spots
4. Keratomalacia
5. Preventable Blindness
6. Skin and Mucous Membrane Lesions

Causes for Vitamin A Deficiency

 Decreased intake.
 Obstructive jaundice causing defective absorption.
 Cirrhosis of liver leading to reduced synthesis of RBP,
 Severe malnutrition, where amino acids are not available for RBP synthesis
 Chronic nephrosis, where RBP is excreted through urine.

Assessment of Deficiency
a. Dark adaptation Test - It is the time required to adapt the eye to see objects in dim light. It is increased
in vitamin A deficiency.
b. RBP (retinol-binding protein) level in serum is decreased.
c. Vitamin A in serum is decreased. The colorimetric measurement is based on Carr and Price reaction,
where retinoids are made to react with antimony trichloride to give a blue color. Vitamin A may be
directly measured by spectrophotometry; it has maximum absorption at 325 nm.
d. Normal blood level of vitamin A is 25 to 50 microgram/dl.

Daily Requirement of Vitamin A

The recommended daily allowance (RDA) for;
a. Children = 400-600 microg/day.
b. Men = 750-1000 microg/day
c. Women = 750 microg/day
d. Pregnancy=1000 microg/day
e. One international unit = 0.3 mg of retinol. One retinol equivalent = 1 microgram of retinol or 6 microgram of
beta carotene.
Dietary Sources of Vitamin A
 Animal sources include milk, butter, cream, cheese, egg yolk and liver. Fish liver oils (cod liver oil and
shark liver oil)
 Vegetable sources contain the yellow pigment beta carotene. Carrot contains significant quantity of beta
carotene. Papaya, mango, pumpkins and green leafy vegetables (spinach, amaranth)

OSTEOMALACI
 A deficiency of vitamin D or an inability to utilize vitamin D may lead to a condition called
osteomalacia (rickets in children), a weakening and softening of the bones brought on by extreme
calcium loss

SOURCES OF VITAMIN D
 Milk
 Sun light
 Eggs
 Mushrooms
 Pork
 Ricotta cheese
 Sole or flounder
 Beef lives
 Cereal

VITAMIN E
 was isolated in wheat germ oil
 Name as tocopherol
 tokos-child birth, pheros-to bear, ol-alcohol
 Vitamin E deficiency in animals result infertility.
✓known to be anti-infertility.
Reminder:
 Most potent b:iological anti-oxid

WHAT IS AN ANTIOXIDANT?
 Antioxidants are substances (chemical compounds) that work in a number of different ways to protect
our cells from 'free radical damage.
 Our skin is constantly under attack from free radicals which damage cells and contribute to ageing and
disease. They are formed from;
 Sunlight
 Lack of sleep
 Pollution
 Chemicals
 Stress
 Cigarette smoke
 Illness
 Bad Diet
 Wishtrend
Free radicals "the threat"
 Natural byproduct of our bodies process (inevitable). However, there are external factors that lead to
more free radicals:

Antioxidant "the guard"

 Help protect cells from the damage by neutralizing the free radicals

Chemical Nature:
 Alpha tocopherol- a chromane ring (tocol) system, with an isoprenoid side chain is present in all the
eight naturally occurring tocopherols. (5,7,8 trimetyl tocol) has greatest biological

ALPHA TOCOPHEROL
 Structure of vitamin E was elucidated by PAUL KARRER, and awareded nobel prize in 1937.

Metabolism of Vitamin E
 Normal blood level is -0.5-1mg/dl.
 Absorbed along with other fats and needs the help of bile salt.
 tocopherol is absorbed and transported as CHYLOMICRONS
 And stored in ADIPOSE TISSUE catabolism, the chromane ring and side chain may be oxidized and
excreted in bile after conjugation with glucuronic acid.
 Metabolism of vitamin E is equally unclear. Excess alpha-tocopherol is converted into alpha CEHC and
excreted in the urine. Other tocopherols, like gamma- and delta tocopherol, are almost quantitatively
degraded and excreted in the urine as the corresponding CEHCS.

Biochemical role of Vitamin E:

 Vitamin E most powerful natural anti-oxidant -free radicals are continuously being generated in living
system
 Ageing process is due to the cumulative effects of free radicals.
 Vitamin E protects RBC from hemolysis. By preventing the peroxidation, it keeps the structural and
functional integrity of all cells.
 Vitamin E also boost immune response
 Reduces the risk of atherosclerosis by reducing oxidation of LDL.
 Vitamin E can depress leukocyte oxidative bacterial activity
 The buildup of fats, cholesterol and other substances in and on your artery walls.

Preventive anti-oxidants: They wil inhibit the initial production of free radicals.

Chain breaking anti-oxidants: They can inhibit propagative phase

SELENIUM
 It is present in glutathione peroxidase; an important enzyme that oxidizes and destroys the free radicals.

SELENIUM
 It has been found to decrease the requirement of vitamin e and vice versa

Generation of free
i. They are constantly produced during the normal oxidation of foodstuffs, due to leaks in the electron transport
chain in mitochondria. About 1-4% of oxygen taken up in the body is converted to free radicals.

II. Some enzymes such as xanthine oxidase and aldehyde oxidase form super oxide anion radical or hydrogen
peroxide.
iii.NADPH oxidase in the inflammatory cells (neutrophils, eosinophils, monocytes and macrophages) produces
superoxide anion by a process of respiratory burst during phago cytosis.

iv.The superoxide and hypochlorous ions are the final effectors of bactericidal action

v. chronic granulomatous disease (CGD), the NADPH oxidase is absent in macrophages and neutrophils

✓They are constantly produced during the normal oxidation of foodstuffs, due to leaks in the electron transport
chain in mitochondria. About 1-4% of oxygen taken up in the body is converted to free radicals.

Generation of free radicals

 Macrophages also produce NO from arginine by the enzyme nitric oxide synthase
 Peroxidation is also catalyzed by lipo oxygenase in platelets and leukocytes.
 lonizing radiation damages tissues by produ cing hydroxyl radicals, hydrogen peroxide and superoxide
anion.
 Light of appropriate wavelengths can cause photolysis of oxygen to produce singlet oxygen.
 The capacity to produce tissue damage by H₂O₂ is minimal

a. Cigarette smoke contains high concentrations of various free radicals.

b. Inhalation of air pollutants will increase the production of free radicals
c. Under hypoxic conditions, the mitochondrial respiratory chain also produce nitric oxide
d. Vitamin E (Alpha tocopherol) acts as the most effective naturally occurring chain breaking anti oxidant
in tissues.

ANTI-OXIDANTS:
1. Vitamin E is the lipid phase antioxidant.
2. Vitamin C is the aqueous phase antioxidant.
3. Ceruloplasmin can act as an antioxidant in extracellular fluid
4. Caffeine is another effective anti-oxidant.
5. Cysteine, glutathione and vitamin A are minor anti oxidants. Beta carotene can act as a chain breaking
antioxidant, but is less effective than alpha tocopherol