Page 233 - Concise Pathology for Exam Preparation ( PDFDrive )

218 SECTION I General Pathology

Sources
Meats (preformed vitamin A) Vegetables (carotenes, provitamin A)
Absorbed as retinol ester and beta carotene by intestinal cells

Transported to the liver as retinol in chylomicrons

Uptake by liver cells through apolipoprotein receptors

Esterification

More than 90% stored in the liver in the Ito cells

Transported to the tissues bound to retinol-binding protein (RBP)
Oxidation
Retinoic acid
Note: The uptake of retinol in the peripheral tissue is dependent on cell surface receptors that are specific
for RBP rather than retinol.
FLOWCHART 9.1. Metabolism of vitamin A.

Functions

1. Visual process: The retina is located at back of the eye. When light passes through the
lens, it is sensed by the retina and converted to a nerve impulse for interpretation by
the brain.
(a) Retinol is transported to the retina via circulation and accumulates in retinal
pigment epithelial cells; retinol is esterified to form a retinyl ester, which can
be stored.
(b) When needed, retinyl esters are broken apart (hydrolysed) and isomerized to form
11-cis-retinol, which can be oxidized to form 11-cis-retinal.
(c) 11-cis-retinal can be shuttled across to rod cells, where it binds to a protein called
opsin to form the visual pigment, rhodopsin (also known as visual purple).
(d) Rod cells with rhodopsin can detect very small amounts of light, making
them important for night vision. Absorption of a photon of light catalyses
isomerization of 11-cis-retinal to all-trans-retinal, and results in its release. This
isomerization triggers a cascade of events, leading to generation of an electrical
signal to optic nerve.
(e) Once released, all-trans-retinal is converted to all-trans-retinol, which can be trans-
ported across retinal epithelial cell, thereby completing the visual cycle.
(f) Inadequate retinol available to the retina results in impaired dark adaptation,
known as ‘night blindness’.
2. Role in orderly differentiation of mucous-secreting epithelium:
(a) All-trans-retinoic acid (ATRA) exerts its effect by binding to retinoic acid receptor
(RAR), which in turn is associated with nuclear receptors for 9-cis-retinoic acid
(RXR) forming RAR/RXR heterodimers. These bind to promoter regions of multiple
genes encoding for growth factors and tumour suppressor genes.
(b) ATRA induces temporary remission of acute promyelocytic leukaemia and the
retinoic acid isomer, 13-cis retinoic acid, has been used in the treatment of neuro-
blastoma.
3. Role in host resistance to infections:
(a) Stimulates the immune system (probably humoral immunity)
(b) Maintains and restores integrity of mucosa

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