VITAMIN A

Retinol

Biologically active forms – retinoids: retinol, retinal, retinoic acid.
Cyclohexane ring and isoprenoid chain
Major vit. A precursor (provitamins) → plants carotenoids.
The foodstuff of animals origin contains most of vit. A in the form of esters (retinylpalmitates) – retinol and long fatty acid

Vitamin A transport and Metabolism

Retinol esters → hydrolysis by pancreatic enzymes to retinol.
b-carotene is cleaved to retinal by b-carotene 15,15´ dioxygenase (cofactors iron and bile salts).
Intestinal cells → esterification of retinol → transported in chylomicrons.
Remnants of chylomicrons → liver→ esterification (if the concentration exceeds 100 mg, esters are stored ).
Transport of retinol to target organs tightly bound to retinol-binding protein, RBP.

A derivative of Vitamin A plays a crucial role in vision when it is bound to a protein called opsin.
The cone cells in the retina of the eye contain several types of opsin and are responsible for vision in bright light and for the color vision.
The rod cells in the retina contain only one type of opsin; they are responsible for vision in dim light.
The aldehyde group of retinal forms a mine with the side chain amino acid group of a lysine residue in the rod cell opsin.
The product is called rhodopsin which occupies 60% of the membrane in rod cells

A is necessary to form rhodopsin (in rodes, night vision) and iodopsins (photopsins, in cones – color vision) – visual pigment.
Retinaldehyde is a prosthetic group of light-sensitive opsin protein.
In the retina, all-trans-retinol is isomerized to 11-cis-retinol → oxidized to 11-cis-retinaldehyde, this reacts with opsin (Lys) → to form the holoprotein rhodopsin.
Absorption of light → conformation changes of opsin → photorhodopsin.
The following is a series of isomerization→ initiation of a nerve impulse.
The final step is hydrolysis to release all-trans-retinaldehyde and opsin.
Deficiency of vit. A leads to night blindness.
Vitamin A is an important antioxidant.

Transcription and cell differentiation

Retinoic acid regulates the transcription of genes – acts through nuclear receptors (steroid-like receptors).
By binding to various nuclear receptors, vit. A stimulates (RAR – retinoic acid receptor) or inhibits (RXR- retinoid „X“ receptor) transcription of genes transcription. All-trans-retinoic acid binds to RAR and 9-cis-retinoic acid binds to RXR.
Retinoic acid is necessary for the function and maintenance of epithelial tissues.

Vitamin A Deficiency

The early sign → a loss of sensitivity to green light,
- prolonged deficiency → impairment to adapt to dim light
- more prolonged deficiency leads to night blindness
- Ever escalated deficiency leads to squamous metaplasia – columnar epithelia are transformed into heavily keratinized squamous epithelia.
The conjunctiva loses mucus-secreting cells → glycoprotein content of the tears is reduced → xerophthalmia (“dry eyes”)
- Often complication – a bacterial or chlamydial infection which results in perforation of the cornea and blindness
Transformation of respiratory epithelium – loss of protective airway function (antibacterial properties) → bronchitis.
Conversion of the urinary tract epithelium → higher frequency of urinary stone formation
Immunosuppression
Impairment of reproductive function (both in men and women).
Worldwide deficiency of vit. A
3 – 10 mil. children become xerophthalmic every year
- 250 000 to 500 000 go to blindness
- 1 million dies from infections

Toxic dose:
- a single dose of more than 200 mg
- more than 40 mg per day
- Acute symptoms – headache, vomiting, impaired consciousness.
Chronic intoxication – weight loss, vomiting, pain in joints, muscles, blurred vision, hair loss, excessive bone growth.
Both vit. A Excess and deficiency in pregnancy are teratogenic – retinoic acid is a gene regulator during early fetal development
Carotenoids are nontoxic – accumulation in tissues rich in lipids (the skin of babies overdosed with carrot juice maybe orange).