Vitamins

  • 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)

    • II.  Absorption

    1. Carotene
      1. Absorbed by humans, cattle, sheep, and chickens, but not by pig and rat.
      2. Requires normal fat absorption
      3. In humans absorption of beta carotene is 40-60% efficient and decreases rapidly with dosage.
    2. Vitamin A
      1. Esters are hydrolyzed in the lumen or at the brush border of small intestines
      2. Retinol in the intestinal cell is esterified primarily with palmitate
      3. Retinyl esters are transported to the systemic circulation by the lymphatic system
      4. Vitamin A is absorbed at 80-90% efficiency

    III.  Metabolism

    1. Most of the beta carotene not converted to retinal is stored in adipocytes
    2. Greater than 90% of vitamin A is stored in liver as retinal esters (acetate, palmitate, etc)
    3. Vitamin A mobilized by hydrolysis of the ester
    4. Bound by retinol binding protein (RBP)
      1. Synthesized by the liver
      2. Binds one mole of retinol
      3. 3Functions to solubilize and stabilize retinol
      4. Complexes with prealbumin, preventing loss of vitamin A via glumerular filtration
      5. Zinc and adequate protein are required for normal production of RBP
      6. RBP is degraded by the kidney
        1. Kidney disease results in urinary excretion
        2. Liver disease results in no synthesis of RBP

    IV.  Metabolic Role

    1. The visual cycle in rod cells
      1. Absorption of light energy by a pigment in the photoreceptor cells in the retina (rhodopsin) to yield a specific photochemical product (all trans retinal)
        1. Rhodopsin is the light absorbing conjugated protein consisting of a protein opsin and tightly bound 11-cis-retinal
        2. When rhodopsin is exposed to light, the bound 11-cis-retinal is transformed to all trans retinal (change in configuration of the retinal molecule).
        3. A series of other molecular changes ends in dissociation of the bleached rhodopsin to free opsin and all trans retinal.
        4. Permeability of vesicle membrane in the rod cells is changed allowing Ca+2 to flow out of the vesicles.
        5. 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.
        6. All trans retinal undergoes isomerization back to 11-cis-retinal.
          1. All trans retinal + NADH + H+  retinal reductase>  all trans retinol + NAD+
          2. All trans retinol  retinol isomerase>  11-cis-retinol
          3. 11-cis-retinol + NAD+  retinol reductase>  11-cis retinal +NADH +H+
        7. 11-cis-retinal recombines with opsin to yield rhodopsin

    V.  Vitamin A Deficiency

    1. Eyes are most conspicuously affected
      1. Xerophthalmia (dry eyes) in children
      2. Abnormal bone development in children (can pinch off optic nerve causing blindness).
      3. Night blindness in adults.
      4. Children are more susceptible than adults because adults have greater liver stores which can last for months or even years.

    VI.  Toxicity

    1. Usually arises from abusive vitamin supplementation or therapy
      1. Single large doses
      2. Chronic long term intake
      3. Symptoms
        1. Anorexia
        2. Dry itchy, desquamating skin
        3. Coarse hair
        4. Conical bone thickening
        5. Enlarged liver, spleen
        6. Double vision
        7. Headaches

    Vitamins




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