Vitamins.

Presented by Disha Mistry

Tutor
Introduction
• Vitamins may be regarded as organic compounds required in the diet in
small amounts to perform specific biological functions for normal
maintenance of optimum growth and health of organism.
• Can be synthesized by by bacterium E.coli and plants, human must obtained
them through diet.
• However the bacteria of the gut (colon region where the absorption is
relatively poor) can produce some of the vitamins, required by man and
animals.
Classification of Vitamins
 Fat Soluble Vitamins vs Water Soluble Vitamins.
Fat soluble Vitamins Water soluble Vitamins
Solubility lipid, oils, fat solvent (alcohol, acetone, Water- soluble
etc.)
Structure Mostly isoprenoid compounds (isoprene Heterogeneous group of compounds
units)
Absorption Similar to fats Similar to polar molecule
Transport Carrier proteins are present No carrier proteins are present
Storage Stored in liver and adipose tissue Not stored in large quantities (except B12) and
hence must be continuously supplied in diet
Excretion Not excreted in urine, & hence excess Readily excreted in urine and hence less likely
intake of these vitamins leads to their to be toxic
accumulation and results in toxic effects
Toxicity Hypervitaminosis may result Unlikely, since excess is excreted
Deficiency Manifests only when stores are depleted Manifests rapidly as there is no storage
Treatment of Single large doses may prevent deficiency Regular dietary supply is required.
deficiency
Terms
• Vitamers : represents the chemically similar substances that possess
qualitatively similar vitamin activity. Examples of vitamers are retinol,
retinal, retinoic acids and β-carotene (vitamers of vitamin A); pyridoxine,
pyridoxal and pyridoxamine (vitamers of vitamin B6)
• Provitamin : biologically inactive compounds which are easily converted
to vitamins in the body (precursor of vitamins). For example, carotenes are
the provitamins of vitamin A. Ergosterol and 7-dehydrocholesterol are the
provitamins of vitamin D.
• Hypervitaminosis : refers to dietary intake of vitamins that exceeds the
ability of body to utilize, store, and excrete it.
 Vitamin A
• Chemistry (Structure)
• Kinetics (Absorption, Transport and Storage)
• Biochemical Functions
• Recommended Dietary Allowance (RDA)
• Dietary Sources
• Deficiency
• Hypervitaminosis
Chemistry.
Fat soluble vitamin A is available in two forms for human needs.
• Retinol : a pre-formed vitamin, occurs only in foods of animal origin – the
liver (stored as retinyl ester with long chain fatty acids) being its richest source.
• β-Carotenes : provitamin found in vegetable foods in plants
The term vitamin A refers to three naturally occurring, structurally similar and
biologically active molecules - Retinol (vitamin A alcohol), Retinal (vitamin A
aldehyde) and Retinoic acid (vitamin A acid)
The term retinoid is often used to includes the natural and synthetic forms with
vitamin A activity.
Structure:
Kinetics (Absorption, Transport and
Storage)
• Absorption :-
A) Retinyl ester are hydrolysed by pancreatic or intestinal brush border
retinyl ester hydrolases in the intestines releasing retinol and free fatty
acids, β-carotenes are hydrolysed by β-carotene 15-15'- dioxygenase of
intestinal cells and is reduced to retinol.
B) After absorption free retinol is re-esterified with long chain fatty acids
within intestinal mucosal cell, further incorporated into chylomicrons and
passed via the lymphatics to the liver to be stored as retinol palmitate.
Transport:-
• The liver holds 90% of vitamin A reserves, and when the need arises retinol
is released from the liver and is transported to peripheral tissues as trans-
retinol by the plasma retinol binding protein (RBP)
• One molecule of RBP binds one molecule of retinol, in case of vitamin A
deficiency the RBP levels in the blood falls.
• The RBP interacts with another protein called as transthyretin (pre-albumin)
to form a trimolecular lipoglycoprotein complex to prevent the loss of
vitamin A by glomerular filteration.
Uptake of cell
• The retinol-RBP complex binds to specific receptor on the retina, skin, gonads, and
other tissues.
• The retinol binds with the cellular retinol binding protein (CRBP) present in
cytoplasm that carries the retinol to the nuclear receptors (RAR and RXR) present
on the nucleus.
• The nuclear receptor when binds with retinol activate the hormone response element
(HRE) which is specific DNA sequence causing their expression (gene transcription)
resulting in the synthesis of specific protein that carry out the ultimate biochemical
functions of vitamin A (normal morphogenesis, growth and cell differentiation).
• The mechanism of action of retinol at the cellular level resembles that of the
steroid hormones.
Biochemical functions

• Vitamin A is necessary for a variety of functions such as vision, proper

growth and differentiation, reproduction, fertility, fetal development,
erythropoiesis, immunity, antioxidant and maintenance of epithelial
cells.
• Infact, specific functions are attributed to different forms of vitamin A
Vitamin A and vision

• The biochemical function of vitamin A in the process of vision was first

elucidated by George Wald and his associates where they studied the
phenomenon of photochemical and biochemical in details and this cyclic
event is hence popularly known as Rhodopsin Cycle or Wald's Visual
Cycle.
• He won the Noble prize in 1968 for it.
Rods and Cones
• The retina of the eyes possess two types of photoreceptor cells- Rods and
Cones
• Rods – 100 millions rods, present in the periphery, extremely sensitive and
respond to low levels of illuminations (dim light vision or perceptions)
• Cones – 5 millions cones, present at the centre of retina, less sensitive and
function only in bright light (daylight vision) and responsible for colour
perception, better suited for rapidly changing visual events because they
responds four times faster than rods.
• The photoreceptor cell contains photosensitive molecule called visual
pigments which is made up of the conjugated integral membrane protein
linked to a prosthetic group.
• Rods – RHODOPSIN ------> opsin + chromophore (11-cis retinal)
• Cones – CONOPSIN ------> conopsin + chromophore (11-cis retinal)
• There are 3 types of cones, each is characterized by the different conopsin
that is maximally sensitive to either --- blue (cyanopsin), green (iodopsin)
or red (porphyropsin).
Dark Adaptation times

• Bright light depletes stores of rhodopsin in rods. Therefore when a person

shifts suddenly from bright light to dimly lit area, there is difficulty in
seeing, for example, entering the cinema theater.
• After few minutes , rhodopsin is resynthesized and vision is improved. This
period is called dark adaptation time.
• The dark adaptation times is increased in vitamin A deficiency.
Other biochemical functions of
vitamin A
• Retinol and retinoic acids acts like a steroid hormones. They regulate the synthesis of
proteins involved in cell growth and differentiation. Vitamin A is required for the normal
reproduction.
• Vitamin A is required for the maintenance of healthy epithelium tissues. It maintains
moist and pliable epithelium by inhibiting the synthesis of excess keratin (responsible
for horny surfaces).
• Retinyl phosphate synthesized from retinoic acids participates in glycoprotein synthesis.
Glycoproteins are important constituents of mucus. In lack of mucus secretion results in
the drying of epithelial tissues.
• Vitamin A is required for the formation of mucopolysaccharides in extracellular matrix.
• Essential for the maintenance of the immune system. Its deficiency causes
keratinisation of mucosal lining of the respiratory, gastrointestinal and
genitourinary tracts, making them susceptible to frequent infections.
• Retinol and retinoic acids are essential for the synthesis of transferrin, the
iron transporting protein. Iron deficiency anemia may occur in vitamin A
deficiency.
Dietary sources

• Vitamin A is widely distributed in animal (retinol) and plant (carotenes)

foods
• Animal foods rich in vitamin A are- liver, whole milk, eggs, butter, cheese,
fish, and meat. Fish liver oil (cod or shark)
• Plant foods are good source of vitamin A- leafy green vegetables such as
spinach, amaranthus available in all seasons and carrots. The darker the
green leaves the higher the carotene contents. Fruits such as papaya,
pumpkin and mango.
RDA
• RDA of Vitamin A is expressed in retinol equivalents (RE). Earlier units was
international units (IU).
• Men – 1000 RE (3500IU)
• Women – 800 RE (2800IU)
• 1RE = 1µg retinol = 6µg carotene
• 1IU = 0.3µg retinol
• The daily requirement of vitamin A is high in growing children, women in
pregnancy and lactation.
• Under normal conditions, a well-nourished person has enough vitamin a
reserves to meet the needs for 6-9 months.
Deficiency manifestation of vitamin A
1) Night blindness or Nyctalopia:
Visual acuity us diminished in dim light. The
patients cannot read or drive car in poor light. The
dark adaptation time is increased.
2) Bitot's spots:
These are seen as grayish- white triangular
plaques firmly adherent to the conjunctiva on
either side of the cornea. This is due to the
thickness of conjunctiva in certain areas. All the
ocular changes mentioned so far are completely
reversible when vitamin is supplemented.
3) Xerophthalmia:
Night blindness, if left untreated causes dryness of
conjunctiva and cornea. The conjunctiva becomes dry,
thick and wrinkled. The conjunctiva gets keratinized and
loses its normal transparency. Dryness spreads to cornea
loses its mucosal cells and become dull, glazy and
lusterless due to keratinization of corneal epithelium.
Infection may supercede.
4) Keratomalacia:
When xeropthalmia persist for a longer periods of time, it
progress to keratomalacia which is ulceration and necrosis
of cornea, which results into total night blindness.
Keratomalacia is one of the major cause of blindness in
developing countries and is usually associated with
protein energy malnutrition.
• Other deficiency manifestation of vitamin A
• Skin lesion occur due to hyperkeratosis, wherein mucus secretion is
decreased, epithelieum is atrophied, increased respiratory, intestima and
genitourinary infections are seen.
• The patients has stunted growth due to defective skeletal formation.
Hypervitaminosis or toxicity
• Consumption of high dose of vitamin A supplementation, often without medical
advice.
• Artic explorers who eat polar bear liver often suffer from acute toxicity of vitamin A
• Symptoms- anorexia, irritability, headaches, drowsiness, vomitting, dry and peeling
of skin, partial hair loss and joint pain.
• Hypercarotenemia can result from persistent excessive consumption of foods rich in
carotenoids. The skin becomes yellow but no staining of sclera as in jaundice is
observed.
• Very high dose of vitamin A during pregnancy are teratogenic and lead to
congenital effects.
 Vitamin D
• Chemistry (Structure)
• Kinetics (Absorption, Transport and Storage)
• Biochemical Functions
• Recommended Dietary Allowance (RDA)
• Dietary Sources
• Deficiency
• Hypervitaminosis
Chemistry
The nutritionally important forms of Vitamin D are -
1) Ergocalciferol (Vitamin D2):- formed from ergosterol present in plants by sunlight.
2) Cholecalciferol (Vitamin D3):- synthesized from 7-dehydrocholesterol (an
intermediate of cholesterol biosynthetic pathway) in the skin (Malpighian layer of
epidermis) on exposure of UV rays from sunlight (photolysis reaction); also found in
animal tissues.
- are provitamins from which active form of vitamin D (Calcitriol) is synthesized.
- undergo the same metabolic changes in the body and have identical biochemical
functions.
-The production of vitamin D in the skin proportional to the exposure to sunlight.
-The pigment melanin which acts as a sunscreen, adversely affects the synthesis of
cholecalciferol.
 Structure
• Represent sterol in structure.
• Both sterols are similar in
structure except that
ergocalciferol has additional
methyl group and a double
bond.
Kinetics
• Dietary sources of vitamin D are absorbed in the small intestine with
the help of bile and enter into circulation through the lymph bound to α 2
globulin and are distributed to the entire body.
• It is stored in small amount in the liver, adipose tissue and muscle.
• Ergocalciferol and cholecalciferol are not biologically active. However
they are further metabolized by the addition of hydroxyl groups, first in
the liver then in the kidney, and are converted to active form of vitamin D.
A) Activation of vitamin D in liver.
• Vitamin D – binding protein (DBP) binds to cholecalciferol and moves it
from the skin and intestine to liver where it gets hydroxylated at the 25th
position to form 25-hydroxycholecalciferol [25(OH)D3].
• Liver enzymes- 25-hydroxylase (microsomal monooxygenase-cytochrome
P450) and requires NADPH and molecular oxygen.
• Major storage form of vitamin D in liver.
• The half-life of 25(OH)D3 in circulation is 2-3 weeks.
25-hydroxylase
Cholecalciferol 25 Hydroxycholecalciferol
A) Activation of vitamin D in Kidney.
• 25-hydroxycholecalciferol binds to DBP and transported to kidney where it
gets hydroxylated at the 1st position to form 1,25-dihydroxycholecalciferol
[1,25(OH2)D3] or [1,25-DHCC] or Calcitriol; which is most potent form of
vitamin D.
• Kidney enzymes- 1α-hydroxylase (mitochondrial monooxygenase-
cytochrome P450) and requires NADPH and molecular oxygen.
• The half-life of 1,25(OH)D3 in circulation is about 4 – 6 hours.

1α-hydroxylase
25(OH)Vitamin D3 1,25 (OH2) vitamin D3
Regulation of synthesis of calcitriol.
• Regulated by the concentration of calcium and phosphate level in blood.
• Low plasma calcium (hypocalcemia) ---> stimulate the parathyroid gland
---> secretion of PTH hormone ---> acts on kidney enhancing calcitriol
synthesis by increasing the 1α-hydrolase activity.
• Low plasma phosphate (hypophosphatemia) ---> increases the activity of
1α-hydrolase enzyme.
• Hypercalcemia and Hyperphosphatemia reduce the activity of 1α-hydrolase
enzyme and lower the level of calcitriol.
• Negative feedback mechanism of calcitriol (homeostasis)