Vitamin A

Vitamin A

• Vitamin A was first vitamin to be discovered, initially as an essential dietary factor for growth.

Vitamin A roles :

• in vision pigments in the retina, cell differentiation Retinol.

• As an antioxidant β- carotene.

functions of vitamin A

Vision Gene transcription Immune function Embryonic development and reproduction Bone metabolism Haematopoieis Skin health Antioxidant activity

Vitamin A

• There are two groups of compounds have vitamin A activity: retinol, retinaldeyde and retinoic acid.

• And a variety ofCarotenes and related compound.

Provitamin A

• Provitamin A carotenoids represent a group of compounds that are pioneers of vitamin A.

• There are three dietary provitamin A carotenoids: β- carotene, α- carotene and β- cryptoxanthin.

Sources

• Vitamin A (retinyl esters) are found in animal origin, the richest source is liver which can pose a potential problems for pregnant women.

• Carotenes are found in green, yellow and red vegetables as well as in liver, margarine, milk and milk products.

Metabolism and storage of vitamin A and pro-vitamin A cartenoids

• Retinol is absorbed from the small intestine dissolved in lipid. About 70-90% of dietary retinol is normally absorbed.

• In people with very low fat intake (less than 10% of energy from fat) absorption of both retinol and carotene is impaired and low fat diets are associated with vitamin A deficiency.

Metabolism and storage of vitamin A and pro-vitamin A carotenoids

• Dietary retinyl esters are hydrolyzed by lipases in the intestinal lumen and mucosal brush border membrane, then re-esterified to form retinyl palmitate before release into the circulation in chylomicrons.

• Most of retinyl esters taken by liver from chylomicron remnants and some by tissues.

• Retinyl esters are hydrolyzed, and the vitamin may either be secreted from the liver bound to retinol binding protein, or to be transferred to stellate cells in the liver, where it is stored as retinyl esters in intracellular lipid droplets.

Vitamine A transport and metabolism

Retinol esters → hydrolysis by pancreatic enzymes to retinol.

β-caroten is cleaved to retinal by β -carotene 15,15´ dioxygenase (cofactors iron and bile salts).

Intestinal cells → esterification of retinol → transported in chylomicrons.

Remnants of chylomicrons → liver→ esterification (if the concentration exceeds 100 mg, esters are stored ).

Transport of retinol to target organs tightly bound to retinol-binding protein, RBP.

Metabolism and storage of vitamin A and pro-vitamin A carotenoids

• Around 50-80% of the total body content of retinol is the stellate cells of the liver, but a significant amount may be stored in adipose tissue.

• The main pathway for catabolism of retinol is oxidation to retinoic acid. The main excretory product of both retinol and retinoic acid is retinoyl glucuronide, which is secreted in the bile.

Metabolism and storage of vitamin A and pro-vitamin A carotenoids

• As the intake of retinol increases, and the liver concentration rise above 70µmol/kg, a different pathway becomes important for catabolism of retinol in the liver.

• This is microsomal cytochrome dependent oxidation, leading to a number of polar metabolites that are excreted in the urine and bile. At high intakes this pathway becomes saturated, and excess retinol is toxic since there is no further capacity for its catabolism and excretion.

The visual Cycle

• Cones in the retina :1. Responsible for vision under bright lights2. Translate objects to color vision.

• Rods in the retina: 1. Responsible for vision in dim lights2. Translate objects to black and white vision.

Visual Pigments

• Composed of two components • Retinal – light absorbing molecule (made from vitamin

A). • Opsin (four types made from protein)• Opsin combined with retinal = visual pigment

(rodopsin)• OPSIN + RETINAL= Visual Pigment• Depending on the type of opsin retinal is bound to,

each of the four pigments will only absorb certain wavelengths of light.

Visual pigments : RODS

• Retinal + Opsin = Rhodopsin (Visual purple)• Absorbs light throughout entire visible light

spectrum (most sensitive to green)• Functions only in dark, dim light & peripheral

vision• Light causes Retinal to change shape &

separate from opsin causing nerve impulse• Regulate only in dark or dim light situations.• Light RHODOPSIN OPSIN RETINAL IMPLULS

Cellular differentiation

• Cell differentiation is the process whereby an immature cell is transformed into a specific type of mature cell.

• Vitamin A as a retinoic acid is needed by many cells for differentiation.

• Vitamin A have a role in gene expression.

Growth

• Retinoic acid appears to increase the number of specific receptors for growth factors.

• The exact mechanism of its role in growth is unclear.

Other function

• Reproductive processes in both males and females need Vitamin A, as retinol.

• Bone development and maintenance. • Vitamin A appears to be involved in iron

distribution among tissues.• Retinoic acid, stimulates phagocytic activity

and cytokine production and maintain natural killer cell concentrations.

Interactions with other nutrients

• Excess vitamin A intake interferes with vitamin K absorption.

• High β-carotene intake, may decrease plasma vitamin E concentration.

• Protein and zinc influence vitamin A status and transport.

• Inadequate protein intake depressing activity of the enzyme carotenoid dioxygenase. Overall vitamin A metabolism is closely related to protein and zinc status.

Interactions with other nutrients

• Vitamin A deficiency is associated with decreased iron incorporation into red blood cells and diminished mobilization of iron from stores. Thus, vitamin A deficiency can be associated with microcytic iron deficiency anemia.

Metabolism and excretion

• The kidney is the main organ responsible for the catabolism and excretion of the vitamin

• Urinary excretion of vitamin A metabolites accounts for up to about 60% of vitamin A excretion.

• Up to 40% of vitamin A metabolites are excreted in the feces.

• In addition, small amount of vitamin A are expired by the lungs as CO2

• Carotenoid metabolites are excreted into the bile for elimination in the feces.

2009 Cengage-Wadsworth

Recommended Dietary Allowance

– 1 RAE(Retinol Activity Equivalent)

= 1 µg retinol = 12 µg -carotene = 24 µg -carotene or -cryptoxanthin= 3.33 IU retinolRDA from Vitamin A – Adult Men: 900 µg RAE; – Adult women: 700 µg RAE– Pregnancy: 770 µg RAE; – lactation: 1,300 µg RAE

Vitamin A - deficiency The early sign → a loss of sensitivity to green light,

prolonged deficiency → impairment to adapt to dim light more prolonged deficiency leads to night blindness

The conjunctiva loses mucus-secreting cells → glykoprotein content of the tears is reduced → xeroftalmia ( „dry eyes“)

Often complication - bacterial or chlamidial infection which results in perforation of the cornea and blindness

Vitamin A - deficiency Transformation of respiratory epithelium – loss of

protective airway function (antibacterial properties) → bronchitis.

Conversion of the urinary tract epithelium → higher frequency of urinary stone formation

Immunosuppression Impairment of reproductive function (both in men and

women).

Worldwide deficiency of vit. A 3 – 10 mil. children become xerophtalmic every year

250 000 to 500 000 go to blindness 1 million die from infections

Vitamin A - toxicity Toxic dose:

single dose of more than 200 mg more than 40 mg per day

Acute symptoms - headache, vomiting, impaired consciousness.

Chronic intoxication – weight loss, vomiting, pain in joints, muscles, blurred vision, hair loss, excessive bone growth.

Both vit. A excess and deficiency in pregnancy are teratogenic – retinoic acid is gene regulator during early fetal development

Carotenoids are non toxic - accumulation in tissues rich in lipids (the skin of babies overdosed with carrot juice may be orange).