By: Akshay Kumar- 76Kamalpreet Kaur- 77

Karanvir Singh Gill- 78Kartik Aggarwal- 79

Khushveen Sidhu -80

VITAMIN A & D

Chemistry of Vit. A i. Vitamin A is fat soluble. The active form is present

only in animal tissues.

ii. The pro-vitamin, beta-carotene is present in plant tissues. Beta carotene has two beta ionone rings connected by a polyprenoid chain.

iii. All the compounds with vitamin A activity are referred to as retinoids. They are polyisoprenoid compounds having a beta-ionone ring system.

iv. Three different compounds with vitamin A activity are retinol (vitamin A alcohol), retinal (vitamin A aldehyde) and retinoic acid (vitamin A acid).

v. The retinal may be reduced to retinol with the help of reductase enzyme.this reaction is reversible.Retinal be reduced to retinol by retinal reductase. This reaction is readily is oxidized to retinoic acid, which cannot be converted back to the other forms.

vi. The side chain contains alternate double bonds, and hence many isomers are possible.The all-trans variety of retinal, also called vitamin A1 is most common.Biologically important compound is 11-cis-retinal.

Absorption of Vit.Ai. Beta carotene is cleaved by a di-oxygenase, to form retinal. The

retinal is reduced to retinol by an NADH or NADPH dependent retinal reductase present in the intestinal mucosa.Intestine is the major site of absorption

ii. The absorption is along with other fats and requires bile salts. In biliary tract obstruction and steatorrhoea, vitamin A absorption is reduced.

iii. Within the mucosal cell, the retinol is reesterified with fatty acids, incorporated into chylomicrons and transported to liver. In the liver stellate cells, vitamin is stored as retinol palmitate.

Transport from liver to tissues

• The vitamin A from liver is transported to peripheral tissues as trans-retinol by the retinol binding protein or RBP . One molecule of RBP binds one molecule of retinol. In the case of vitamin A deficiency, the RBP level in blood falls.

Uptake by tissues• The retinol-RBP complex binds to specific

receptors on the retina, skin, gonads and other tissues. The RBP does not enter in the cell. Inside the cytoplasm of cells, vitamin binds to cellular retinoic acid binding protein (CRBP) and finally to hormone responsive elements of DNA.Thus, genes are activated.

• VISUAL CYCLES• GENE TRANSCRIPTION• MAINTENANCE OF EPITHELIAL CELLS• DERMATOLOGY• REPRODUCTION

FUNCTIONS OF VITAMIN ABY KARTIK AGGARWAL

VISUAL CYCLES• Component of rods & cone cells.• Rhodopsin, the visual pigment, consists of 11-

cis retinal bound to opsin.• Rhodopsin is needed to see in low light

(contrast) as well as for night vision.• Rhodopsin

Rhodopsin exposed to

lightBleaching &

release of all-trans retinal &

opsin

All-trans retinal reduced to all-

trans retinolAll-trans retinol

esterified & isomerized to 11-cis retinol

11-cis retinol oxidizes to

11-cis retinal

11-cis retinal combines with opsin to form RHODOPSIN

Excitation of nerve

All-trans retinol dehydrogenase

Lecuithin transacetylase & isomerohydrolase

11-cis-retinoldehydrogenase

Maintenance of epithelial cells

• Essential for normal differentiation of epithelial tissue and mucous secretion

• Supports body’s barrier-based defence against pathogens. Thus contribute to the IMMUNE SYSTEM of the body.

reproduction• Retinol and retinal are essential for normal

reproduction• Supports Spermatogenesis in males and

prevents Fetal Resorption In Females.• Retinoic acid promotes growth and

differentiation of epithelial cells

Animals given vitamin A only as retinoic acid from birth are blind and sterile

dermatology• Retionic acid maintain normal skin health by

switching on genes and differentiating keratinocytes (immature skin cells) into mature epidermal cells.

• For the treatment of acne, the most prescribed retinoid drug is 13-cis retinoic acid known as isotretinoin.

Specific functions of diff. forms

• Retinol Reproduction Regulates synthesis of proteins involved in cell growth & diffentiation. Functions as Steroid Hormone

• Retinoic acid Cell growth & differentiation Synthesis of glycoproteins by forming Retinoyl phosphate Inhibits enzyme Collagenase & prevents breakdown of collagen

• Both Regulation of gene Expression Synthesis of Transferrin (Fe transporter) Maintenance of Immune System Construction of normal bones & teeth Treatment of Acne Cholesterol synthesis

Retionoids & carotenoids have anticancer activity.β - carotene functions as antioxidant & free radical

scavenger thus reducing risk of cancer &heart attacks.

requirements• Daily requirement is expressed as Retinol

Equivalents (RE). 1RE=1μg retinol & 6μg of β-carotene 1IU=0.3μg retinol & 0.6μg of β-carotene• 1000RE in males (3500IU)• 800RE in females (2800IU)• Req. increases in pregnancy, lactation, growing

children & hepatic diseases.

sources• Animal sources- Fish Liver oil, Egg yolk, Butter, Cheese, Kidney, Liver• Plant sources- Pigmented vegetables especially yellow & green, Pumpkin, Sweet potato, Carrot.

DEFICIENCY OF VITAMIN A

Vitamin A deficiency can result from inadequate intake, fat malabsorption, or liver disorders. Deficiency impairs immunity and causes rashes and ocular effects (eg, xerophthalmia, night blindness). Diagnosis is based on ocular findings and low vitamin A levels. Treatment consists of vitamin A given orally

TYPES OF VITAMIN A DEFICIENCY • Primary vitamin A deficiency is usually caused by Prolonged dietary deprivation Xerophthalmia due to primary deficiency is a common cause of

blindness .It is common in counteries where the diet contains low amount of beta carotene

• Secondary vitamin A deficiency may be due toDecreased bioavailability of provitamin A carotenoidsInterference with absorption, storage, or transport of vitamin AInterference with absorption or storage is likely in celiac disease,

cystic fibrosis, pancreatic insufficiency,duodenal bypass, chronic diarrhea, bile duct obstruction, and

cirrhosis.

DEFICIENCY MANIFESTATIONS OF VITAMIN A

• Night blindness• xerophthalmia• bitot’s spot• keratomalacia• preventable blindness• skin and mucous membrane lesions

NIGHTBLINDNESS• Nightblindness is not a disease but a symptom of vitamin A

deficiency• Night blindness (nyctalopia) is a type of vision impairment.• It is one of the earliest symptoms of vitamin A deficiency .• People with night blindness experience poor vision at night or

in dimly lit environments.• the patients suffering from night blindness cannot read or

drive car in poor light .• The dark adaptation time is increased .• Prolonged deficiency irreversibly damages a number of visual

cells

XEROPHTHALMIA• Xerophthalmia is caused by a severe vitamin A deficiency is described

by dryness of the conjunctiva and cornea. The eye fails to produce tears.

• The conjunctiva becomes dry, thick and wrinkled. If untreated, it can lead to corneal ulceration and ultimately to blindness as a result of corneal damage.

• Treatment can occur in two ways: treating symptoms and treating the deficiency.

• Treatment of symptoms usually includes use of artificial tears in the form of eye drops, increasing the humidity of the environment with

humidifiers, and wearing wrap around glasses when outdoors. • Treatment of the deficiency can be accomplished with a Vitamin A or

multivitamin supplement or by eating foods rich in Vitamin A.

KERATOMALACIA • Keratomalacia is drying and clouding of the cornea due to

vitamin A deficiency and usually insufficient protein and calories in the diet.

• The surface of the conjunctiva and cornea dries, sometimes leading to corneal ulcers and bacterial infections.

• The tear glands are also affected, resulting in an inadequate tear film and dry eyes. People with extreme eye dryness can develop foamy spots on the conjunctiva. Night blindness may develop because of the effects of vitamin A deficiency on the retina.

• The diagnosis of keratomalacia is based on the presence of a dry or ulcerated cornea in an undernourished person

BITOT’S SPOT

• Bitot's spots are the buildup of keratin located superficially in the conjunctiva, which are oval, triangular orirregular in shape.

• These spots are a sign of vitamin A deficiency

PREVENTABLE BLINDNESS

• The deficiency of vitamin A is the most common cause of blindness in indian children below the age of 5 .

• About 40% of the blindness is preventable . Vitamin A deficiency is a major public health problem .

• A dose of vitamin A , is given as a prophylactic measure ,to children below 1 year age.

SKIN MUCOUS MEMBRANE LESIONS

• Follicular hyperkeratosis results from hyperkeratinization of the epithelium lining of follicles .The skin becomes rough .Keratinising metaplasia of epithelium of the respiratory ,gastrointestinal,and genitourinary tracts have been observed . Epithelium is atrophied .

• Keratinisation of urinary tract epithelium may lead to urinary calculi .

• The alterations in skin may cause increased occurance of generalised infections .

• Isoretinone , is used prevent acne formation during adolescence as it reduces sebaceous secretions

PREVENTION

• The diet should include dark green leafy vegetables, deep- or bright-colored fruits (eg, papayas, oranges), carrots, and yellow vegetables (eg, squash, pumpkin). Vitamin A–fortified milk and cereals, liver, egg yolks,and fish liver oils are helpful. Carotenoids are absorbed better when consumed with some dietary fat.

VITAMIN A TOXICITY • Hypervitaminosis A refers to any number of a

large amount of toxic effects from ingesting too much of Vitamin A.

Vitamin A toxicity can be • Chronic • Acute

ACUTE TOXICITY OF VITAMIN A

• Acute vitamin A toxicity in children may result from taking large doses , usually accidentally.

• During acute vitamin A toxicity the patient suffers from headache and acute intracranial pressure.

• It also causes nausea and vomiting.

CHRONIC VITAMIN A TOXICITY

• Chronic toxicity in older children and adults usually develops after doses of have been taken for month

• Chronic toxicity causes changes in skin, hair, and nails; abnormal liver test results; and, in a foetus, birthdefects .The patients also suffer from head ache and acute intracranial pressure

• Calcitriol has target organs-intestine,bone and kidney, where it specifically acts.

• Calcitriol synthesis is regulated by a feedback mechanism ie calcitriol decreases its own synthesis.

Deficiency symptoms of vit d

• Insufficient exposure to sunlight and consumption of diet lacking vit d results in its deficiency.

• Vit d deficiency occurs in strict vegetarians,chronic alcoholics,individuals with liver and kidney diseases.in some people,who cover the entire body for religious customs,vitamin d deficiency is also observed, if the requirement is not met through diet.

.deficiency of vit d causes rickets in children and osteomalacia in adults.

.rickets in children is characterized by;1.Bone deformities due to incomplete mineralisation

resulting in soft and pliable bone and delay in the tooth formation.

2.Weight bearing bones are bent to form bow legs.3.The plasma level of calcitriol is decrease.4.Alkaline phosphatase activity is

elevated.overproduction of alkaline phosphatase related to more cellular activity of the bone.

5.In case of osteomalacia demineralization of the bones occurs[bones becomes softer] increases the risk to fractures.

• Renal rickets [renal osteodystrophy];this is seen in renal failure. Renal rickets is mainly due to decreased synthesis of calcitriol in kidney.it can be treated by administration.

• Hypervitaminosis d It can result from inadequate sunlight

exposure,disorders limiting vit d absorption and conditions impairing vit d conversion into active metabolities including certain liver,kidney and hereditary disorders.

it includes; 1.demineralization of bone[resorption] and 2.increased calcium absorption from intestine

leading to elevated calcium in plasma[hypercalcemia]

• 3.prolonged hypercalcemia is associated with deposition of calcium in many soft tissues such as kidney and arteries.

• 4.Its may leads to formation of stones in kidneys.• 5.High consumption of vit d is associated with loss

of appetite,nausea,increased thirst,loss of weight.

Biochemical functions• Calcitriol the biologically active form of vit D

regulates the plasma level of calcium and phosphate

• Calcitriol acts at 3 different level to maintain plasma calcuim.

• 1 action of calcitriol on the intestine• 2 action of calcitriol on the bone• 3 action of calcitriol on the kidney

Action of calcitiol on the intestine

• calcitriol increases the intestinal absorption of calcium and phosphate.

• In the intestinal cells calcitriol binds with a cytosolic receptor to form a calcitriol receptor complex

• This complex then approches the nucleus and interacts with a specific DNA leading to the synthesis of a specific calcium binding protein which increases the calcium uptake by the intestine.

Action of calcitriol on the bone

• In the osteobtlasts of bone, calcitriol stimulates calcium uptake for deposition as calcium phosphate.

• Calcitriol along with parathyroid hormone increases the mobilization of calcium and phosphate from the bone.This causes elevation in plasma calcium and phosphate.

Vitamin d is a hormone and not a vitamin -justification

• Catcitriol is considered as an important calciotropic hormone.

• Vit d3 [cholecalciferol] is synthesized in the skin by UV rays of sunlight.

• calcitriol[ [biologically active form of vit d] is produced in kidney.

• Calcitriol action is similar to steriod hormones.it binds to a receptor in the cytosol and the complex acts on DNA to stimulates the synthesis of calcium binding protein.

Action of calcitriol on the kidney

• In the kidney convertion of 25-hydroxy-cholecalcifirol to calcitriol takes place with the help of enzyme 1-hydroxylase

• Calcitriol minimizes the excretion of calcium and phosphate through the kidney, by decreasing their excretion and enhancing reabsorption.