vitamin a, sources, functions, deficiency

2.  Vitamin A is a fat soluble vitamin
 It’s active form is found only in animal
tissues
 RETINOIDS-include vit.A and natural
and synthetic chemicals that are
structurally related to it
 Those with Vit.A activity are
retinol,retinal and retinoic acid
 CAROTENOIDS(30%)-are provitamins
of plant origin that can be metabolised
to active Vit.A

3.  Metabolism of vit.A-
 Absorption-bile,pancreatic enzymes.
 Both retinol& β-carotene(later converted to
retinol)is absorbed in intestine and carried in
chylomicrons to liver
 Receptor in liver-apoprotein-E
 90% stored in liver as retinol ester in
perisinusoidal stellate cells(Ito)
 In healthy persons – 6 month reserves

4.  mobilisation of retinol ester –retinol binds to
specific RBP synthesized in liver
 Uptake by peripheral tissuesdepends upon
specific RBP receptors;retinol binds to
cellular RBP and RBP released into blood
 Retinol stored as retinol ester or converted to
retinoic acid

6.  Maintenance of normal vision
 Cell growth and differentiation
 Metabolic effects of retinoids
 Host resistance to infections

7.  Vision involves vitamin A containing
rhodopsin and 3 iodopsin
 SYNTHESIS OF RHODOPSIN
o Oxidation of retinol to all-trans-retinal
o Isomerisation to-11-cis-retinal
o Covalent association with 7-transmembrane
rod protein opsin to form rhodopsin

8.  MECHANISM OF VISION
o Photoexcitation causes splitting of rhodopsin
and isomerization of 11-cis-retinal to all-trans-
retinal
o Conformational change in opsinseries of
eventsnerve impulse from retina to brain
o In Dark adaptation,all-trans-retinal converted to
11-cis-retinal which is reduced to retinol and lost
in retina continuous supply

9.  Orderly differentiation of mucus-secreting
epithelium
 Deficiency-squamous metaplasia-
keratinizing epithelium
 Activation of retinoic acid recerptos by their
ligands causes release of corepressors and
formation of heterodimers with retinoic x
receptor

10.  RAR/RXR heterodimers bind to retinoic acid
response elements located in regulatory
gene regions that encode receptors for
GFs,tumor suppresor genes and secreted
proteins
 Thus retinoids(all-trans-retinoic acid- highest
affinity for RARs)control cell
growth,differentiation,cell cycle control and
other biologic responses

11.  RXR(activated by 9-cis retinoic acid) form
heterodimers with nuclear receptors involved in
drug metabolism,PPARS,and vitamin D
receptors
 Peroxisome proliferator-activated receptors
regulate fatty acid oxidation in fat tissue and
muscle,adipogenesis,and lipoprotein
metabolism
 Association b/w RXR and PPARγ-explanation for
matabolic effects of retinoids on adipogenesis

12.  Diarrhea-maintenance and restoration of
integrity of epithelium of gut
 Measles-stimulation of immune system
 Infections inhibit RBP synthesis in liver
through acute phase response,causing a
decrease in circulating retinol leadind to
reduced bioavailability of Vit.A

13.  Retinoids and carotenoids are photoprotective
and antioxidant agents
 Retinoids used for treatment of severe
acne,psoriasis,acute promyelocytic leukemia
 All-trans-retinoic acid induces differentiation and
apopotosis if apl cells by binding to PML-RARβ
fusion protein that characterises this form of cancer
 13-cis retinoic acid –treatment of childhood
neuroblastoma

14.  Vitamin deficiency may be primary or
secondary
 Primary- due to dietary deficiency of the
vitamin
 Secondary-due to disturbances in intestinal
absorption,transport in blood,tissue
storage,or metabolic conversion

15.  In children stores of vit.A are depleted by
infection
 In adults malabsorption syndromes such as
celiac disease,Crohn disease,colitis,may
develop vit.A deficiency
 Bariatric surgery and continuous use of
mineral oil as laxative lead to deficiency

16.  Impaired vision in reduced light-night blindness
 Persistant deficiency leads to epithelial
metaplasia and keratinisation
 Effects on EYE:
 Xerophthalmia(dry eye)-it is due to replacement
of normal lacrimal and mucus secreting
epithelium by keratinized epithelium
 Bitots spot-devolopment of keratin debris in
small opaque plaques
 Keratomalacia-bitots spot progresses to erosion
of corneal surface,softening and destruction of
cornea and blindness

18.  Loss of mucociliary epithelium of the airways
predisposes to secondary pulmonary infection
 Devolopment of keratin debris in urinary tract
predisposes to renal and bladder stones
 Hyperkeratinisation of epidermis with plugging
of ducts of adnexal glands produce follicular or
papular dermatosis
 Vit.A deficiency also produce immune
deficiency,making the individual susceptible to
infections measles,pneumonia,and infectious
diarrhea

19.  Symptoms of acute Vit.A toxicity(similar to
brain tumor) include:
Headache
Dizziness
Vomiting
Stupor and
Blurred vision

20.  Chronic toxicity produces:
Weight loss
Anorexia
Nausea
Vomiting
Bone and joint pain
• Retinoic acid stimulates osteoclast
production and activity leading to bone
resorption and risk of fractures
• Synthetic retinoids have teratogenic effects

21. THANKYO
U