Which of the following form of Vitamin A has maximum effects on DNA?
Correct Answer: Isoretinoic acid
Description: Ans. B. Isoretinoic acid. (Ref Harrison 18th/Ch. 74; 17th/pg. 446-447; Guyton Physiology 11thtpg. 629)In pregnancy, the daily dose of vitamin A should not exceed 3 mg. Commercially available retinoid derivatives are also toxic, including 13-cis-retinoic acid, which has been associated with birth defects. As a result, contraception should be continued for a least 1 year, and possibly longer, in women who have taken 13-cis retinoic acid.Vitamin A# In the strictest sense, refers to retinol.# However, the oxidized metabolites, retinaldehyde and retinoic acid, are also biologically active compounds. The term retinoids includes all molecules (including synthetic molecules) that are chemically related to retinol.# Retinaldehyde (11-cis) is the essential form of vitamin A that is required for normal vision, whereas retinoic acid is necessary for normal morphogenesis, growth, and cell differentiation. Retinoic acid does not function in vision and, in contrast to retinol, is not involved in reproduction.# Vitamin A also plays a role in iron utilization, humoral immunity, T cell-mediated immunity, natural killer cell activity, and phagocytosis. Vitamin A is commercially available in esterified forms (e.g., acetate, palmitate) since it is more stable as an ester.# ?-Carotene is the most prevalent carotenoid in the food supply that has provitamin A activity. It is now estimated that 12 ?g or greater of dietary ?-carotene is equivalent to 1 ?g of retinol, whereas 24 ?g or greater of other dietary provitamin A carotenoids (e.g., cryptoxanthin, ?-carotene) is equivalent to 1 ?g of retinol.# Retinoic acid is a ligand for certain nuclear receptors that act as transcription factors. Two families of receptors (RAR and RXR receptors) are active in retinoid-mediated gene transcription.# Vitamin A is needed to form the visual pigments and, therefore, to prevent night blindness.# Vitamin A is also necessary for normal growth of most cells of the body and especially for normal growth and proliferation of the different types of epithelial cells. When vitamin A is lacking, the epithelial structures of the body tend to become stratified and keratinized.# Vitamin A deficiency manifests itself bx:(1) scaliness of the skin and sometimes acne;(2) failure of growth of young animals, including cessation of skeletal growth;(3) failure of reproduction, associated especially with atrophy of the germinal epithelium of the testes and sometimes with interruption of the female sexual cycle; and(4) keratinization of the cornea, with resultant corneal opacity and blindness.# In vitamin A deficiency, the damaged epithelial structures often become infected, for example, the conjunctivae of the eyes, the linings of the urinary tract, and the respiratory passages. Vitamin A has been called an "anti-infection" vitamin.# Toxicity# Acute toxicity of vitamin A was first noted in Arctic explorers who ate polar bear liver and has also been seen after administration of 150 mg in adults or 100 mg in children.# Acute toxicity is manifested by increased intracranial pressure, vertigo, diplopia, bulging fontanels in children, seizures, and exfoliative dermatitis; it may result in death. In children being treated for vitamin A deficiency according to the protocols outlined above, transient bulging of fontanels occurs in 2% of infants, and transient nausea, vomiting, and headache occur in 5% of preschoolers.# Chronic vitamin A intoxication is largely a concern in industrialized countries and has been seen in normal adults who ingest 15 mg/d and children who ingest 6 mg/d of vitamin A over a period of several months. Manifestations include dry skin, cheilosis, glossitis, vomiting, alopecia, bone demineralization and pain, hypercalcemia, lymph node enlargement, hyperlipidemia, amenorrhea, and features of pseudotumor cerebri with increased intracranial pressure and papilledema. Liver fibrosis with portal hypertension and bone demineralization may result from chronic vitamin A intoxication. When vitamin A is provided in excess to pregnant women, congenital mal- formations have included spontaneous abortions, craniofacial abnormalities, and valvular heart disease.# High doses of carotenoids do not result in toxic symptoms but should be avoided in smokers due to an increased risk of lung cancer. Carotenemia, which is characterized by a yellowing of the skin (creases of the palms and soles) but not the sclerae, may be present after ingestion of >30 mg of ?-carotene daily. Hypothyroid patients are particularly susceptible to the development of carotenemia due to impaired breakdown of carotene to vitamin A. Reduction of carotenes from the diet results in the disappearance of skin yellowing and carotenemia over a period of 30-60 days.Human teratogenic drugsDrugAbnormalityThalidomidePhocomelia, Multiple defectsAnticancer drugs (methotrexate)Cleft palate, hydrocephalus, multiple defects, foetal deathAndrogensVirilization; limb, esophageal, cardiac defectsProgestinsVirilization of female foetusStiboestrolVaginal carcinoma in teenage female offspringTetracyclinesDiscoloured and deformed teeth, retarded bone growthWarfarinDepressed nose; eye and hand defects, growth retardationPhenytoinHypoplastic phalanges, sleft lip/palate, microcephalyPheenobarbitoneVariousmalformationsCarbamazepineNeural tube defects, other abnormalitiesValproate sodSpina bifida and other neural tube defectsAlcoholLow IQ baby, growth retardation, foetal alcohol syndromeACE inhibitorsHypoplasia of organs, growth retardation, foetal lossLithiumFoetal goiter, cardiac and other abnormalitiesAntithyroid drugsFoetal goiter and hypothyroidismIndomethacin/aspirinPremature closure of ductus arteriosusIsotretinoinCraniofacial, heart and CNS defects.
Category:
Biochemistry
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