- Biologically active forms – retinoids: retinol, retinal, retinoic acid.
- 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.
Cone cells vs Rod Cells
- 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
Vitamin A and Vision
- 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.
Vitamin A and other Functions
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
- 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
Vitamin A Toxicity
- 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).
Metabolic Function of Vitamin A
- Gene transcription
- Immune function
- Embryonic development and reproduction
- Bone metabolism
- Skin health
- Antioxidant activity
Sources of Vitamin A
- Cod liver oil
- Dairy products