3VITAMIN AVITAMIN A :- Is widely distributed inanimal and plant foodsanimals –pre-formed – Retinol.plants – pro-formed - carotene
VITAMIN A Exits in 3 forms:all trans-retinollong chain fatty acyl ester of retinol (mainstorage form)retinal (the active form in the retina) retinoic acid is also considered to bephysiologically active provitamin A or carotene can be converted toretinol in vivo
CH3CH3H3CCH3H3C CH3H3CCH3CH3CH3β-caroteneCH3CH3H3CCH3CH3OHCH3CH3H3CCH3CH3OHliverO2retinal (active form in vision)CH3CH3H3CCH3CH3OCOOHCH3CH3H3CCH3CH3retinoic acid ("hormonally-activeform")ROvitamin A acetate (R = CH3)vitamin A palmitate (R = C16H33retinol (from diet)
Vitamin A6Lots of double bonds, good anti-oxidant
VITAMIN A & CAROTENOIDSDigestion & absorptionVitamin A requires digestionRetinol bound to fatty acid estersRetinyl esters & carotenes oftencomplexed with protein2009 Cengage-Wadsworth
Emulsification of fat globulesRetinol absorbed via proteincarrierCarotenoids absorbed viatransporters & passive diffusion
VITAMIN A & CAROTENOIDSCarotenoids & retinoids metabolizedin enterocytes to some extentRetinol esterified & incorporated intochylomicrons for transportCellular retinol-binding protein(CRBP) II2009 Cengage-Wadsworth
Transport, metabolism, &storageChylomicrons carry to liverAdditional metabolism in liver
Carotenoids transported as partof lipoproteinsCarotenoids stored in liver &adipose
VITAMIN A & CAROTENOIDSRetinol that is esterified may bestored in the liver Stellate cells & parenchymal cellsTransported in blood via 2proteins Retinol-binding protein (RBP) Tranthyretin (TTR)2009 Cengage-Wadsworth
19 Approximately 80% is absorbed. It is passed along with fat through thelymphatic system into blood stream. absorption is poor in case of diarrhea,jaundice and abdominal disorder.
absorption increases if taken withfat. vitamin A which is not absorbed isexcreted within 1 or 2 days in feces .
21ABSORPTION & STORAGE The liver has enoromous capacity tostore – in the form of retinolpalmitate. under normal conditions a well-fedperson has sufficient Vitamin Areserves to meet his need for 6 to 9months or more. Free retinol is highly active buttoxic & therefore transported inblood stream in combination withretinol binding protein (liver)
VITAMIN A & CAROTENOIDSFunctions & mechanisms of actionVitamin A Vision - rhodopsin Cellular differentiation Gene expression Growth Other functions - reproduction, bonemetabolism2009 Cengage-Wadsworth
ADDITIONAL ROLE OF RETINOLretinol also functions in the synthesis ofcertain glycoproteins andmucopolysaccharides necessary formucous production and normal growthregulationthis is accomplished by phosphorylationof retinol to retinyl phosphate whichthen functions similarly to dolicholphosphate
BIOLOGICAL ROLE OF VITAMIN-A1. Retinol and retinoic acid have rolein normal reproduction2. Retinal has a role in visual cycle3. Retinoic acid has a role inglycoprotein synthesis4. Roll in MPS synthesis
5. Vitamin-A is needed formitochondrial membrane function6. Anti cancer role: β-carotene is anantioxidant and trap peroxy free radicalsin tissues at low partial pressure of O27. Bone and teeth formation
27DAILY REQUIRMENT Men and women – 600 mcg. Pregnancy and lactation – 950 mcg. Infants – 350mcg. Children – 600mcg.(RECOMMENDE BY ICMR – 1989)
31VISION Retinal is a necessarystructural component ofrhodopsin or visual purple,the light sensitive pigmentwithin rod and cone cells ofthe retina. If inadequatequantities of vitamin A arepresent, vision is impaired.
32EPITHELIAL CELL "INTEGRITY Many epithelial cells appear to require vitaminA for proper differentiation and maintenance. Lack of vitamin A leads to dysfunction of manyepithelia - the skin becomes keratinized andscaly, and mucus secretion is suppressed. Itseems likely that many of these effects are dueto impaired transcriptional regulation due todeficits in retinoic acid signalling.
Fig. 11-4, p. 372Vitamin A maintainshealthy cells in themucous membranes.Without vitamin A, thenormal structure andfunction of the cells inthe mucous membranesare impaired.Mucus Goblet cellsStepped Art
34Reproduction: Normal levels of vitamin A is required for spermproduction, Normal reproductive cycles in females require adequateavailability of vitamin A.Bone remodeling: Normal functioning of osteoblasts and osteoclasts isdependent upon vitamin A.
40RESISTANCE TO INFECTIOUS DISEASE In almost every infectious disease studied,vitamin A deficiency has been shown toincrease the frequency and severity ofdisease.
Several large trials with malnourishedchildren have demonstrated dramaticreductions in mortality from diseases such asmeasles by the simple and inexpensiveprocedure of providing vitamin Asupplementation.
42THE SIGNS OF VITAMIN A DEFICIENCYOcular Night blindness. Conjunctival xerosis bitot’s spot Corneal xerosis keratomalaciaExtra ocular Retarded growth Skin disorders Effect onreproductive organs. Effect on bone
43NIGHT BLINDNESS Lack of vitamin A causes nightblindness or inability to see indim light. night blindness occurs as a resultof inadequate pigment in theretina. It also called tunnel vision. Night blindness is also found inpregnant women in someinstances, especially during thelast trimester of pregnancy whenthe vitamin A needs areincreased.
50KERATOMALACIA One of the major causefor blindness in India. cornea becomes soft andmay burst open . The process is rapid If the eye collapsesvision is lost.
51INCREASED RISK OF MORTALITYFROM INFECTIOUS DISEASEIt has been best studied in malnourished children,but also is seen in animals. In such cases,supplementation with vitamin A has beenshown to substantially reduce mortality fromdiseases such as measles and gastrointestinalinfections.
HYPERVITAMINOSIS AExcess of vitamin A induce series of toxiceffects known as hypervitaminosis Asyndrome. Seen usually amongEskimos who consume livers of polarbear and arctic foxes.
53HYPRRVITAMINOSIS AIf the daily dose > 30,000mcgtoxic symptoms:- painful joint thickening of long bones.
anorexia low grade fever rashes irregular menstruation fatigue. loss of hair
55CAROTENEMIA A condition in which conversionof carotene to vitamin A isimpaired by inborn metabolic erroror hepatic diseases generalized yellowish skin andmucosa. excessive deposition of carotenewhich is result of high intake offoods containing carotene.
VITAMIN ASOURCESAnimal sources•Liver oil•Butter•Milk•Cheese•Egg yolkPlant sources•Tomatoes•Carrot•Green-yellow vegetables•Spinach•Mangoes•Papaya•Corn•Sweet potatoRDA: Adults 3000-5000 IU/dayChildren, pregnant and lactating women
sources:Retinol is found in liver, wholemilk, cheese and butter.Carotenes are found in milk,carrots, dark green leafyvegetables and orange colouredfruits, e.g. mango and apricots.
60TREATMENT vitamin deficiency should be treated urgently . depending upon deficiency symptoms it is given inthe dose of 7,500 to 15,000 mcg per day for onemonth nearly all of the early stages of xerophthalmia can bereversed by administration of a massive dose –2,00000 IU or 110mg orally on two successive days(30). If Hypervitaminosis restriction of diet