Retinoid

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The retinoids are a class of chemical compounds that are related chemically to vitamin A. Retinoids are used in medicine, primarily due to the way they regulate epithelial cell growth.

Retinoids have many important and diverse functions throughout the body including roles in vision, regulation of cell proliferation and differentiation, growth of bone tissue, immune function, and activation of tumor suppressor genes.

Research is also being done into their ability to treat skin cancers. Currently 9-cis retinoic acid may be used topically to help treat skin lesions from Kaposi's sarcoma.

Contents 1 Types 2 Structure 3 Absorption 4 Uses 5 Toxicity 6 References 7 See also 8 External links

[edit] Types

There are three generations of Retinoids:

• First generation retinoids: which include retinol, retinal, tretinoin (retinoic acid, Retin-A), isotretinoin and alitretinoin.

• Second generation retinoids: which include etretinate and its metabolite acitretin.

• Third generation retinoids: which include tazarotene , bexarotene and Adapalene.

[edit] Structure

The basic structure of the retinoid molecule consist of a cyclic end group, a polyene side chain and a polar end group. The conjugated system formed by alternating C=C double bonds in the polyene side chain are responsible for the color of retinoids (typically yellow, orange, or red). Hence, many retinoids are chromophores. Alternation of side chains and end groups creates the various classes of retinoids.

First and Second generation retinoids are able to bind with several retinoid receptors due to the flexibility imparted by their alternating single and double bonds.

Third generation retinoids are less flexible than First and Second generation retinoids and therefore, interact with fewer retinoid receptors.

[edit] Absorption

The major source of retinoids from the diet are retinyl esters derived from animal sources. Retinyl esters are hydrolyzed in the intestinal lumen to yield free retinol and the corresponding fatty acid (i.e. palmitate or stearate). After hydrolysis, retinol is taken up by the enterocytes. Retinyl ester hydrolysis requires the presence of bile salts that serve to solubilize the retinyl esters in mixed micelles and to activate the hydrolyzing enzymes ^[1]

Several enzymes that are present in the intestinal lumen may be involved in the hydrolysis of dietary retinyl esters. Cholesterol esterase is secreted into the intestinal lumen from the pancreas and has been shown in vitro to display retinyl ester hydrolase activity. In addition, a retinyl ester hydrolase that is intrinsic to the brush-border membrane of the small intestine has been characterized in the rat as well as in the human. The different hydrolyzing enzymes are activated by different types of bile salts and have distinct substrate specificites. For example, whereas the pancreatic estrase is selective for short-chain retinyl esters, the brush-border membrane enzyme preferentially hydrolyzes retinyl esters containing a long-chain fatty acid such as palmitate or stearate. Retinol enters the absorptive cells of the small intestine, preferentially in the all-trans-retinol form .

[edit] Uses

Retinoids are used in the treatment of many diverse diseases and are effective in the treatment of a number of dermatological conditions such as inflammatory skin disorders^{[citation needed]}, skin cancers^{[citation needed]}, disorders of increased cell turnover (e.g. psoriasis)^{[citation needed]}, and photoaging^{[citation needed]}.

Common skin conditions treated by retinoids include acne and psoriasis^{[citation needed]}.

[edit] Toxicity

Toxic effects occur with prolonged high intake (in children 25,000-500,000 IU daily[citation needed]). A medical sign of chronic poisoning is the presence of painful tender swellings on the long bones. Anorexia, skin lesions, hair loss, hepatosplenomegaly, papilloedema, bleeding, general malaise, pseudotumor cerebri, and death may also occur.

Chronic overdose also causes an increased liability of biological membranes and of the outer layer of the skin to peel.[citation needed]

Recent research [citation needed] has suggested a role for retinoids in cutaneous adverse effects for a variety of drugs including the Antimalarial drug proguanil. It is proposed that drugs such as proguanil act to disrupt retinoid homeostasis.

[edit] References

1. ^ Noy, N. (2006) "Vitamin A", "Biochemical, Physiological, & Molecular Aspects of Human Nutrition", M. H. Stipanuk 2nd Ed.

• The Pharmacological Basis of Therapeutics -Goodman & Gilman 10th EDT.

• Clinical Pharmacology -P.N. Bennett & M.J. Brown

[edit] See also

• Adapalene
• Hypervitaminosis A syndrome
• Biotinylated retinoids

[edit] External links

• MeSH Retinoids

v • d • e Carotenoids Carotenes: Carotene (Alpha-carotene · Beta-carotene)  · Lycopene · Phytoene • Phytofluene · Neurosporene Retinoids: Acitretin · Alitretinoin · Bexarotene · Etretinate · Fenretinide · Isotretinoin · Retinaldehyde · Tazarotene · Vitamin A (Retinol, Tretinoin) Xanthophylls: Antheraxanthin · Astaxanthin · Canthaxanthin · Citranaxanthin · Cryptoxanthin · Diadinoxanthin · Diatoxanthin · Dinoxanthin  · Flavoxanthin · Fucoxanthin · Lutein · Neoxanthin · Rhodoxanthin · Rubixanthin · Violaxanthin · Zeaxanthin

v • d • e Acne-treating agents (D10) Topical agents Azelaic acid • Benzoyl peroxide • Glycolic acid • Light therapy • Salicylic acid • Tea tree oil Antibiotics Clindamycin • Erythromycin • Sulfacetamide • Tetracyclines • Trimethoprim Hormonal Antiandrogens • Contraceptives Retinoids Adapalene • Isotretinoin • Tazarotene • Tretinoin

v • d • e Antipsoriatics (D05) Topical: tars Tar Topical: antracens Dithranol Topical: psoralens Trioxysalen - Methoxsalen Topical: other Fumaric acid - vitamin D (Calcipotriol, Calcitriol, Tacalcitol) - Tazarotene Systemic: psoralens Trioxysalen - Methoxsalen - Bergapten Systemic: retinoids Etretinate - Acitretin