||Vitamin A & Carotenes
Vitamin A Deficiency
- Vitamin A includes all ?ß-ione derivatives, other than provitamin A carotenoids, exhibiting qualitatively the biological activity of all trans retinal. (J Nutr. 109:8-15, 1979)
- Vitamin A, all transretinol (R=CH2OH)
- Retinal, R=CHO
- Retinoic acid, R=COOH
- Retinal esters, R=COOR
- Vitamin A2, dehydroretin(ol)(al)(oic acid)
- Carotenoids (provitamin A)
- All carotenoids exhibiting qualitatively the biological activity of ß-carotene.
- Alpha, Beta, and Gamma
- Relative biological potency (S.L. Ames, 1962, Feedstuffs)
- All trans vitamin A......100
- Beta carotene.............trans....100 cis.....38
- Alpha carotene...........trans.....53 cis.....13
- Gamma carotene.......trans.....42 cis.....19
- Cryptoxanthin.............trans.....57 cis......27
- Carotenoids are usually cleaved at the 15-15' double bond.
- This forms 2 all trans retinaldehydes.
- Activity of the enzyme 15-15' carotenoid dioxygenase is decreased by low protein intake (protein deficiency contributes to vitamin A deficiency)
- Absorbed by humans, cattle, sheep, and chickens, but not by pig and rat.
- Requires normal fat absorption
- In humans absorption of beta carotene is 40-60% efficient and decreases rapidly with dosage.
- Vitamin A
- Esters are hydrolyzed in the lumen or at the brush border of small intestines
- Retinol in the intestinal cell is esterified primarily with palmitate
- Retinyl esters are transported to the systemic circulation by the lymphatic system
- Vitamin A is absorbed at 80-90% efficiency
- Most of the beta carotene not converted to retinal is stored in adipocytes
- Greater than 90% of vitamin A is stored in liver as retinal esters (acetate, palmitate, etc)
- Vitamin A mobilized by hydrolysis of the ester
- Bound by retinol binding protein (RBP)
- Synthesized by the liver
- Binds one mole of retinol
- 3Functions to solubilize and stabilize retinol
- Complexes with prealbumin, preventing loss of vitamin A via glumerular filtration
- Zinc and adequate protein are required for normal production of RBP
- RBP is degraded by the kidney
- Kidney disease results in urinary excretion
- Liver disease results in no synthesis of RBP
IV. Metabolic Role
- The visual cycle in rod cells
- Absorption of light energy by a pigment in the photoreceptor cells in the retina (rhodopsin) to yield a specific photochemical product (all trans retinal)
- Rhodopsin is the light absorbing conjugated protein consisting of a protein opsin and tightly bound 11-cis-retinal
- When rhodopsin is exposed to light, the bound 11-cis-retinal is transformed to all trans retinal (change in configuration of the retinal molecule).
- A series of other molecular changes ends in dissociation of the bleached rhodopsin to free opsin and all trans retinal.
- Permeability of vesicle membrane in the rod cells is changed allowing Ca+2 to flow out of the vesicles.
- Ca+2 serves as a messenger for coupling the exciting stimulus (conformation change) to the function of the receptor system. The nerve impulse is triggered.
- All trans retinal undergoes isomerization back to 11-cis-retinal.
- All trans retinal + NADH + H+ retinal reductase> all trans retinol + NAD+
- All trans retinol retinol isomerase> 11-cis-retinol
- 11-cis-retinol + NAD+ retinol reductase> 11-cis retinal +NADH +H+
- 11-cis-retinal recombines with opsin to yield rhodopsin
V. Vitamin A Deficiency
- Eyes are most conspicuously affected
- Xerophthalmia (dry eyes) in children
- Abnormal bone development in children (can pinch off optic nerve causing blindness).
- Night blindness in adults.
- Children are more susceptible than adults because adults have greater liver stores which can last for months or even years.
- Usually arises from abusive vitamin supplementation or therapy
- Single large doses
- Chronic long term intake
- Dry itchy, desquamating skin
- Coarse hair
- Conical bone thickening
- Enlarged liver, spleen
- Double vision
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