Fat-Soluble Vitamins Vitamin A
The active forms of vitamin A are retinol, retinaldehyde, and retinoic acid. These substances are synthesized by plants as the more complex carotenoids which is cleaved to retinol by most animals and stored in the liver as retinol palmitate. Biochemical functions promoted:
Only in the case of vision is the biochemistry well understood. Vitamin A becomes reversibly associated with the visual pigments in the D11-cis-retinal form. When light strikes the retina, a number of biochemical changes take place, resulting in a nerve impulse, conversion of the retinal to the all-trans form, and dissociation from the visual pigment. Regeneration of more visual pigment requires isomerization back to the D11-cis-form. Some of this material can be regenerated in a slow process in the retina and by other pathways involving retinal reductase in the eye and retinal isomerase in the liver. Other important metabolic roles have been identified to require vitamin A; they are bone development and cell growth, reproduction, health of epithelial cells, and maintaining stability of cell membranes. Carotenoids appear to lower the risk of getting cancer. Deficiency: http://bob.usuhs.mil/biochem/nutriti...-6-1-icon.jpeg http://bob.usuhs.mil/biochem/nutriti...sis-1-icon.jpg
Since vitamin A is stored in the liver, deficiencies of this vitamin can develop only over prolonged periods of inadequate uptake. Mild vitamin A deficiencies are characterized by follicular hyperkeratosis (rough keratinized skin resembling "goosebumps"), anemia and increased susceptibility to infection. http://bob.usuhs.mil/biochem/nutriti...ind-1-icon.jpg http://bob.usuhs.mil/biochem/nutriti...ind-2-icon.jpg
Night blindness is also an early symptom. http://bob.usuhs.mil/biochem/nutriti...cia-1-icon.jpg
Severe vitamin A deficiency leads to progressive keratinization of the cornea of the eye. This condition is known as Bitot's spots in its mildest form (localized spots), xerosis conjunctivae in moderately severe form and xerophthalmia in its most advanced stages. In final stages, infection usually sets in, with resulting hemorrhaging of the eye and permanent loss of vision. Absorption and Metabolism:
Both vitamin A and carotenoids are fat soluble. Preformed vitamin A in food is usually present as retinyl palmitate which has to be hydrolyzed by pancreatic enzymes before absorption by the intestinal mucosa cell as retinol. The carotenoids are absorbed intact in the presence of bile salts and are converted to retinol by a cleavage enzyme in the intestinal mucosa cell. The retinol is then esterified with palmitic acid in the intestinal mucosa cells, and the retinyl palmitate is then incorporated in chylomicrons and carried into the blood stream via the thoracic duct. Retinyl palmitate is stored in the liver. Figure below - Mechanism of vitamin A absorption and hormone action.
Key: RBP, retinol binding protein; CRBP, cellular retinol binding protein; CRABP, cellular retinoic acid binding protein; Rx, retinoid receptor; RAR, retinol (or retinoid) receptor; IBRP, retinoid binding protein in retina; CM, chylomicrons; RApoE, receptor for CM remnants; TTR, transthyretin; +, stimulates transcription. Sources and requirement:
Preformed vitamin A is available only in animal products which include liver, kidney, cream, butter, and egg yolk. The major dietary sources of the provitamin is yellow and green vegetables and fruits.
Recommended allowance for vitamin A is 1000 retinol equivalents for adult males and 800 retinol units for adult females. One retinol equivalent is defined to be equal to 1 mg of retinol or 6 mg of b- carotene or 12 mg of other provitamin A carotenoids. Requirements are different for infants, children, pregnant and lactating women.
Doses of 15,000 to 50,000 retinol equivalents per day of preformed vitamin A over a period of months or a single dose of 350,000 IU have been proved to be toxic for children and adults. The usual symptoms include headache, dizziness, nausea, vomiting, diarrhea, scaly dermatitis, enlargement of liver and spleen, and hydrocephalus (abnormal accumulation of fluid in the cranial cavity, results in enlargement of the head, atrophy of the brain and convulsion). Excessive intake of carotenes (carotenoids) does not appear to be harmful even though it may result in deposition of yellow pigments in the soles of the feet, palms of the hands, and nasolabial folds.
Because of the toxicity that can be induced by high concentrations of vitamin A, the FDA has imposed a ceiling of 2000 retinol equivalents or l0,000 IU (international units) on the amount of vitamin A that can be included in a multivitamin preparation available without prescription.