Fat soluble Vitamines

2 groups
1. Water soluble
2. Fat soluble-stored in live and fatty tissues
Eliminated more slowly than water soluble
vitamins
Pose greater risk for toxicity when taken n
excess.
VITAMIN A
Ak.a retinol
2 main components in foods are :
a. Retinol
b. Carotenoids
Retinoids include:
a. Retinal(retinaldehyde)
b. Retinoic acid
c. Retinyl esters (retinyl acetate, retinyl
palmitate, retinyl propionate)
Actions

Essential for normal function of retina-visual

adaptation to darkness
Retinol & retinoic acid are necessary for
maintaining :
a. Structural and functional integrity of
epithelial tissue & immune system
b. Cellular differentiation & proliferation
c. Bone growth
d. Testicular and ovarian function
e. Embryonic development
May act as a cofactor in biochemical reactions

Absorptions
Readily absorbed from upper gastrointestinal
tract (duodenum & jejunum)
Requires the presence of:
a. gastric juice,
b. bile salts,
c.
pancreatic and intestinal lipase,
d. protein and dietary fat
Distribution and Elimination
90% stored in the liver
Small amounts are stored in the kidney &
lungs
Transported in the blood with a carries-retinol
binding protein(RBP)
Eliminated in the bile or urine(as metabolites)
Appears in breastmilk.
Bioavailability

Deficiency

Absorption is reduced if the intake of dietary

fat is <5 g daily and by the presence of
peroxidised fat and other oxidizing agents in
food.
Deficiencies of these affects transport, storage&
utilization:
a. Protein
b. Vitamin E
c. Zinc
d. Excess alcohol

Widespread in young children

Assoc. w/ general malnutrition
Xerophthalmia (can be irreversible)
a. Conjunctival & corneal xerosis
b. Ulceration & liquefaction
Ultimately severe visual impairment and
blindness
Night blindness
Dryness of the skin and popular
Metaplasia and keratinization of the cells of
the resp. tract .
Increased susceptibility to respiratory and
urinary tract infections
Occasionally diarrhea and loss of appetite.

Pregnancy & breastfeeding

Excess doses of vit A =teratogenic
Adverse effects
acute toxixity may be nduced by single doses of
300g retinol(1mil.units)
adults 60 mg retinol 200 000 units,
children 30mg retinol 100 000 in infants
a. headache
b. sore mouth
c. bleeding gums
d. dizziness
e. vomiting
f. blurred vision
g. hepatomegaly
h. irritability
i. bulging of the fontanelle
signs of toxicity may appear when daily intake
is >15mg retinol(50,000 units)in adults and 6
mg(20000 units in infants and young children.)
most signs and symptoms disappear w/n a
week but skina dn bone changes may remain
evident fr several months.
Signs
a. dryness of the skin
b. pruritis
c. dermatitis
d. skin desquamation

e.
f.
g.
h.
i.
j.
k.
l.
m.
n.

skin erythema
skin rash
skin scaliness
papilloedema
disturbed hair growth
fissure of the lips
bone and joint pain
hyperostosis
headache
fatigue, irritability, insomnia, nausea weightloss
hypercalsemia.

Interaction
anticoagulants large doses may induce a
hypoprothrombinaemic response.
Colesttyramine and colestipol=reduces
intestinal absorption of vit.A
Colchicine=reduces intestinal absorption.
Neomycin=reduces intestinal absorption of
vit.A
Statins =prolonged therapy with statins
mayincrease serum vit. A levels
Sucralfate=reduces intestinal absorption of
Vit.A
1.
2.
3.
4.
5.
6.

Iron =in vitamin A deficiency, plasma iron level fall

Vit. C = tissue levels of vitamin C may be reduced
and urinary excretion of vitamin C increase,
Vitamin C mmay ameliorate the toxic effect of vit.
A
Vitamin E = large doses of Vit. A increase the need
for vit. E
Vitamin E = protects against the oxidative
destruction of vit. A
Vitamin K = under conditions of hypervitaminosis
A., hypothrombinaemia may occur.it can be
corrected by administration of vit. K.

VITAMIN D
Sterols exhibit the biological activity of
CHOLECALCIFEROL:
a. Vit. D1 (calciferol)
b. Vit. D2 (ergocalciferol)
c. Vit. D3 (colecalciferol)
d. 1 (OH) D3 (1hydroxycholecalciderol;alfacalciferol)
1,25(OH)2D3 (1,25dihydroxycholecalciferol;calcitriol)
25(OH) D3 (25dihydroxycholecalciferol;calcitriol)
24,25(OH)2 D3 (24,25-dihydroxycholecalciferol)
Dihydrotachysterol.
CUTANEOUS SYNTHESIS

Exposure of the skin to UV rays results in:

a. Synthesis of cholecalciferol (vit. D3)
major source of Vit. D
Amount obtained depends on:
a. Length of exposure
b. Area of skin exposed
c. Wavelength of UV light
d. Pollution
e. Skin pigmentation
f. Age

Action

Promotes absorption and utilization of Ca2+

and P2 and normal calcification of skeleton.

Along w/ parathyroid hormone and

calcitonin, it regulates serum ca2+

concentration by altering serum ca2+ and
phosphate blood levels as needed and
mobilizing ca2+ fr. Bone
Maintains neuromuscular function and various
other cellular processes, including the immune
system and insulin production.

Absorption

Absorbed with the aid of bile salts from the

small intestine via the lymphatic system and
its associated chylomicrons

Efficiency is about 50%

Distribution
Vitamin D is converted by hydroxylation to 25
(OH)D3major circulating form of Vit. D.
From the liver, 25(OH)D3 is transported to
kidney and converted by further hydroxylation
to 1,25 (OH) D3 by the metablically active form
and to 24,25)OH)2D3.
Synthesis is regulated mainly by circulating
levels of 1,25(OH)2D3.

Synthesis is also stimulated by :

a. Hypocalcaemia
b. Hypophosphataemia
c. Parathyroid hormone(PTH)

Inhibited by:
a. Hyper-calcaemia
24,25 (OH)2D3-=produced in the kidney,
second metabolite of Vit.D.
Both 1, 25(OH)2D3 & 24,25(OH)2D3 may be
required for biological activity of vitamin D.
Transported in the plasma bound to a specific
vitamin D-binding protein= w/c is its main
storage form.
Small amounts are stored in the liver and
adipose tissue, which may cause a relative
deficiency in obese people.


Deficiency

Some are excreted in breastmilk.

Results in adequate intestinal absorption of

calcium and phosphate:
a. hypocalcaemia and
b. hypophospataemia and
c. increase serum alkaline phosphatase
activity and
d. hyperparathyroidism.
Demineralization of bone leads to rickets in
children and osteomalacia in adults
Infants may develop convulsions and tetany.

VITAMIN E
Family of eight naturally occurring homologues
that are synthesized by plants fr. Homogentisic
acid.
All are derivative of 6-chromanol and differ in
the number and position of methyl groups on
the ring structure.
An example of a phenolic antioxidant.

Early diagnostic signs of deficiency:

a. Leakage of muscle enzymes such as creatine kinase
& pyruvate kinase into plasma
b. Increased levels of lipid peroxidation products in
plasma
c. Increased erythrocyte haemolysis
VITAMIN K
Biological role of vit.K is to act as a cofactor for
a specific carboxylation reaction that
transforms selective glutamate residues to gg
carboxyglutamate(Gla) residues (1,2)Catalyzed by:
a. Microsomal enzyme
b. Gg-glutamyl
c. Vitamin K dependent carboxylase
w/c in turn linked to salvage pathway known as
vit.K epoxide xycle.

Major biologic role of vit E is to protect PUFAs

and ther components of cell membranes and
low-density lipprotein fr. Oxidation by free
radicals.
Located primarily w/n the phospholipid bilayer
of cell membranes
Effective in oreventing lipid peroxidation, a
series of chemical reactions involving the
oxidative deterioration of PUFAs
Absorption depends from the:
a. Adequate pancreatic function
b. Biliary secretion
c. Micelle formation
Condition for absorption are like those for
dietary lipids:
a. Efficient emulsification
b. Solubilisation w/n mixed bile salts micelle
c. Uptake by enterocytes
d. Secretion into the circulation via lymphatic
system.

Transported in the blood by plasma

lipoproteins and erythrocytes
Chylomicrons carry tocopherol from the
enterocyte to the liver, where they are
incorporated into parenchymal cells as
chylomicron remnants.

Muscle and neurological problems are also a

consequence of human vit. E deficiency.

PHYLLOQUINONE= absorbed chemically

unchanged from the proximal intestine after
solubilisation into mixed micelles composed of
bile salts and the products of pancreatic
lipolysis.

In healthy adults, efficiency of absorption is

80%.
w/n intestinal mucosa the vitamin s
incorporated into chylomicrons, secreted into
lymph and enters the blood via the lacteals.

Phylloquinonethe major circulating form of

vit.K but MK-7 is present in plasma at lower
concentrations and has a lipoprotein
distribution similar t phylloquione.
Human liver stores
a. 90% menaquinones
b. 10% phylloquinone(very labile)
Other sites of storage
a. Adipose tissue
b. Bone
Extensively metabolized in liver

Excreted in kidney and bile.

60-70% are absorbed from each meal
Best sourcegreen leafy veg.& veg oil.
Intestinal microflora synthesize amounts of
menaquinone w/c are potentially available as a
source of vit.K.

Menaquinones are present in distal colon

Major forms produced

MK-10
MK-11

Bacteroides

MK-8

Enterobacter

MK-6

Eubacterium lentum

MLK-7

Veillonella

When taken orally natural vit K seem free of excess side

effects.