Vitamin A (Retinol)

liver and kidney
November 14, 2013

Vitamin A is actually a family of similar compounds, the retinoids, that are related to retinol. Apparently, retinoic acid performs most of the functions of vitamin A, binding to DNA receptors in target cells. You can see the diagram of this and it might make more sense.

There are 4 biologically important retinoids:

  • Retinol– the alcohol form. Retinol esters are packaged into chylomicrons and transported to the liver for storage. When retinol is released from the liver, it complexes with retinol binding protein (RBP) and is delivered to target tissues throughout the body (except heart and skeletal muscle). In the cytosol, retinol is irreversibly oxidized to retinoic acid (similar to steroid hormones) which binds to nuclear receptors forming a complex which activates gene transcription of protein products .
  • Retinal– the oxidized form of retinol. The two are readily convertable. Retinal is a component of the visual pigments within rod and cone cells of the retina (see below).
  • Retinoic Acid– the oxidized form of retinal. It cannot be reduced in the body. Thus, it cannot give rise to retinol or retinal. It has wide pharmacologic therapies in dermatology.
  • b-carotene– plant form of vitamin A. Oxidatively cleaved (via thyroid hormone) in the intestine to 2 molecules of retinal. Unfortunately, this conversion process is inefficient and the vitamin A activity of b-carotene is only about 1/6 that of retinol.

RDA: for adults- 1000 retinol equivalents (RE) for males and 800 RE for females. One RE=1 mg of retinol; 6 mg of b-carotene; or 12 mg of other carotenoids.

Good sources of Vitamin A: liver, kidney, cream, butter, and egg yolks have pre-formed vitamin A. Yellow and dark green vegetables and fruits are good sources of carotenes.

Functions of Vitamin A: The functions of vitamin A can be divided into four categories.

  • Visual Cycle- see this in the diagram below.
  • Growth- Absence of vitamin A prevents bone growth from keeping up with the growth of nervous tissue and can lead to CNS damage. Also, there is a hyper-keratinization of the taste buds on the tongue which decreases the person’s appetite (at first anyway).
  • Reproduction- prevents fetal resorption in the female and supports spermatogenesis in the male. Retinoic acid doesn’t help here or with the visual cycle. Therefore, if anyone has only had retinoic acid since birth, they are blind and sterile.
  • Maintenance of Epithelial Cells- you gotta have this stuff for epithelial differentiation and mucous secretion.
  • active forms of vitamin A are used in the treatment of skin disorders and acute progranulocytic leukemia (M3)
    • • topical tretinoin (all-trans-retinoic acid) is used in the treatment of psoriasis and mild acne
    • • oral isotretinoin is used to treat severe acne, however, it is teratogenic, so women must have a pregnancy test before it is prescribed and must be placed on birth control pills for the full duration of therapy 0 is used to treat acute progranulocytic (promyelocytic) leu emia (M3) and is thought to induce maturation of the leukemic cells
    • Retinoic acid as a pharmacotherapeutic- effective treatment of acne and psoriasis. Everything I have seen states that you have to use an all trans retinoic acid (tretinoin) which is too toxic for systemic use and must only be applied topically. However, if the pt doesn’t respond to this therapy, and if they have a severe case, you can use isotretinoin (13-cis retinoic acid) orally.
  • b-carotene- Populations that consume increased amounts of b-carotene also have a reduction in heart disease and lung and skin cancer. These effects are independent of b-carotene being a precursor to vitamin A and probably due to its antioxidant effects (see oxidative damage). b-carotene, unlike vitamin A, is not toxic even at high doses.

Toxicity: Some would argue that this can be the most toxic of the vitamins. You shouldn’t exceed 7.5 m. An excess of b-carotenes in the diet turns the skin yellow, however, the sclera remain white and signs of vitamin A toxicity do not occur

Deficiency Symptoms: Night blindness (nyctalopia), xerophthalmia (dryness of the cornea & conjunctiva – can lead to blindness), dry-rough skin, follicular keratosis, bronchogenic carcinoma (squamous metaplasia may progress to dysplasia & cancer), poor wound healing, & impaired bone growth. Vitamin A deficiency is the most common deficiency in the world and the 2nd leading cause of blindness (second only to Chlamydia trachomatis).

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