Biochemistry of Vitamin A and Vitamin D

1. Ahmad Guelleh
BScN, MSN, B.Eng.
Ahmad Guelleh

2. Vitamin A and D
Ahmad Guelleh

3.  Vitamin A (e.g, retinol, retinaldehyde, retinoic acid) is
found in fish oils, meats, dairy
products, and eggs.
β-Carotene, a precursor of vitamin A, which is
metabolized by intestinal mucosal cells into
retinaldehyde, is found in green vegetables.
Ahmad Guelleh

4.  Vitamin A in the form of retinol is absorbed into the
intestinal mucosal cells and is transported to the liver
via chylomicrons.
In the liver, vitamin A is stored in Ito cells, which are
located in the space of Disse.
Ito cells contribute to cirrhosis by secreting transforming
growth factor beta (TGF-β) and promoting fibrosis.
Vitamin A is delivered to the rest of the body via
prealbumin and retinol-binding protein.
Ahmad Guelleh

5.  Vitamin A combines with opsin in the eye to form
rhodopsin in the rod cells of the
retina.
A similar reaction produces iodopsin in cone cells. These
proteins play a crucial role in sensing light in the retina
and are essential for vision.
Vitamin A also has a role in the differentiation and
proliferation of epithelial cells in the respiratory tract,
skin, cornea, conjunctiva, and other tissues.
Ahmad Guelleh

6.  Deficiency of vitamin A, therefore, causes vision
problems, disorders of epithelial cell
differentiation and proliferation, and impaired immune
response.
Visual symptoms are usually the first sign of vitamin A
deficiency, which include loss of green light sensitivity,
poor adaptation to dim light, and night blindness (loss
of retinol in rod cells).
Ahmad Guelleh

7.  Xerophthalmia (squamous epithelial
thickening), Bitot spots (squamous
metaplasia) and keratomalacia also
occur in vitamin A deficiency.
Ahmad Guelleh

8.  Keratomalacia is metaplasia of the conjunctival
lining, which leads to a change from a thin squamous
lining to a keratinized, stratified squamous epithelium.
Metaplasia of respiratory epithelia is seen
(often common in cystic fibrosis due to failure of fat-
soluble vitamin absorption), as well as frequent
respiratory infections (secondary to respiratory
epithelial defects).
Ahmad Guelleh

9. Because vitamin A is stored in the liver and is lipophilic, the
body can store large amounts of the vitamin. Toxicity can
occur acutely, chronically, or as a teratogenic effect.
Acute toxicity can be caused from a large, single dose of
vitamin A and results in nausea, vertigo, and blurry vision.
Chronic toxicity can manifest as ataxia, alopecia,
hyperlipidemia, edema, or hepatotoxicity. Excess vitamin A
also can turn the skin yellow, but this can be distinguished
from jaundice because the sclera remain white.
Ahmad Guelleh

10.  Vitamin D plays an important role in bone metabolism
by regulating plasma calcium concentrations.
 Vitamin D is absorbed from dietary sources (saltwater
fish and egg yolks) and is also synthesized in the skin.
 Vitamin D absorption is regulated by serum calcium
concentrations.
Ahmad Guelleh

11.  In the presence of UV light, 7dehydrocholesterol
present in the skin is converted to previtamin D.
 Once previtamin D is formed, it is converted to
cholecalciferol, which enters the circulation.
 Activation of cholecalciferol takes place in the liver
and the kidney.
Ahmad Guelleh

12.  The liver converts cholecalciferol to 25
hydroxycholecalciferol. The kidney converts 25-
hydroxycholecalciferol into 1,25-
hydroxycholecalciferol (1,25 OHD, calcitriol), its
active metabolite.
The kidney also converts 25-hydroxycholecalciferol into
24,25-hydroxycholecalciferol, an inactive metabolite
(Figure 2-80).
 Vitamin D–binding globulin stores vitamin D and is
also responsible for its transport in the circulation.
Ahmad Guelleh

13. Ahmad Guelleh

14.  negative feedback effect on its own production and
PTH production. In excess, 1,25-
hydroxycholecalciferol also promotes the production of
24,25-dihydroxyvitamin D.
Ahmad Guelleh

15.  In the presence of excess calcitriol and thus calcium from
either bone or intestinal absorption, high levels of calcium
act to decrease PTH production, and high levels of
phosphate act to decrease conversion of 25
hydroxycholecalciferol to 1,25-hydroxycholecalciferol
by blocking the 1α-hydroxylase enzyme (found in the kidney)
involved in the activation of the 25-hydroxy derivative
(Figures 2-81 and 2-82).
Ahmad Guelleh

16.  Deficiency of vitamin D leads to rickets in children
and osteomalacia in adults, with the differences being
open (in children) and closed (in adults) epiphyseal
plates.
Rickets results from not receiving enough calcium and
phosphate at the sites where bone mineralization is
taking place.
Ahmad Guelleh

17.  Clinically, children with rickets show signs of
hypocalcemia, bowing of the lower
extremities, and poor dentition. Other signs
include pigeon breast deformity, frontal
bossing, rachitic rosary (knobs of bone at
costochondral joints), and bowing of the legs.
 The treatment for vitamin D–deficient rickets
and osteomalacia is vitamin D therapy.
Ahmad Guelleh

18.  CalciTRIol works on the TRIad of
intestines, kidneys, and bone to maintain
plasma calcium levels.
Ahmad Guelleh

19.  Vitamin D maintains the plasma calcium concentration
by increasing intestinal absorption of calcium,
minimizing calcium excretion in the distal renal
tubules, and mobilizing bone mineral in bones.
 It also stimulates osteoblasts and improves
calcification of bone matrix (and, hence, bone
formation).
Ahmad Guelleh

20.  Activated vitamin D binds to a nuclear receptor in cells
(intestinal cells, renal cells, and osteoblasts) and induces
gene expression.
 It is regulated by a series of feedback mechanisms
involving parathyroid hormone (PTH), calcium, and
phosphate.
 Low levels of calcium stimulate PTH synthesis and
secretion, which in turn prompt the conversion of 25-
hydroxycholecalciferol
to 1,25-hydroxycholecalciferol.
Ahmad Guelleh

21.  In turn, 1,25-hydroxycholecalciferol has a negative
feedback effect on its own production and PTH
production.
 In excess, 1,25-hydroxycholecalciferol also promotes
the production of 24,25-dihydroxyvitamin D.
Ahmad Guelleh

22. Ahmad Guelleh

23. Thank you
Ahmad Guelleh