VITAMIN A

Retinol

• 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
• 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

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

• Vision
• Gene transcription
• Immune function
• Embryonic development and reproduction
• Bone metabolism
• Hematopoiesis
• Skin health
• Antioxidant activity

Sources of Vitamin A

• Cod liver oil
• Meat
• Egg
• Milk
• Dairy products
• Carrot
• Broccoli
• Spinach
• Papaya
• Apricots