Which vitamin in large doses is teratogenic?
Correct Answer: Vitamin A
Description: Ans. is 'a' i.e., Vitamin A* Vitamin A is absorbed along intestine and is stored as retinyl esters. Retinyl esters are hydrolysed in liver and is released as retinol (ol - alcohol) into circulation* Retinol is transported as retinol bound to retinol binding protein and is taken up by tissues and is converted by alcohol dehydrogenase and by aldehyde dehydrogenase to form retinal (al - aldehyde) and then retinoic acid (acid)* Retnoic acid then binds to two classes of retinoic acid receptors - RAR (Retinoic acid A receptor) and RXR (Retinoic acid X receptor)* RAR and RXR are transcription factors* They bind to specific regions and regulate expression of various genes related to growth and development of tissues* Retinoids contribute to expression of Hox gene. Hox gene is involved in axial skeleton development* Hence excess retinoids disrupt the genetic control of axial patterning in developing embryo - affecting spinal cord (spinabifida) and brain (microcephaly, anencephaly)* It has been found that exposure of embryos during gestational age 2 through 6 days present with more abnormalities* Use of certain artificial derivatives of retinoic acid prove to be more dangerous than natural forms. Intake of 13-cis-retinoic acid by women during pregnancy for example, results in developmental irregularities in fetuses and children, such as cleft palates, absent or abnormally small ears, heart defects, and thymus abnormalities. For children whose mother were exposed to Etretinate, which is similar to 13-cis-retinoic acid, they exhibit limb defects as well as cardiac and thymus abnormalities. The risk of fetal malformations from exposure to etretinate persists for a longer period of time after the pregnant women's exposure to the substance ends because etretinate stores in her deep body compartments, especially fat depots, and has an extremely long half life (120 days) in the human body. 13-cis-retinoic acid has a shorter half life than etretinate.
Category:
Biochemistry
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