Lec:4
Fat soluble vitamins:They are present in food fats: fatty meats, liver, dairy fats, egg yolk, vegetable seed oil, and leafy green vegetables. These vitamins are metabolized along with fat in the body. They are digested with fat, require fat for absorption, are transported with fat in chylomicrons and lipoproteins or by attached to specific binding proteins, and stored in the liver or in adipose tissue. The fat (lipid) soluble vitamins have diverse functions: e.g., vitamin A, vision ; vitamin D , calcium and phosphate metabolism; vitamin E, antioxidant; vitamin K, blood clotting.
Vitamin A:
Sources:Commonly found in cod liver oil, green vegetables, and fruit. Carrots indirectly serve as a source of vitamin A since they contain β- carotene which the body readily converts to vitamin A.
Vitamin A consists of three biologically active molecules, retinol, retinal (retinaldehyde) and retinoic acid.
INCLUDEPICTURE "I:\\Biochemisy_2003 (G)\\dll\\alltransretinal.jpg" \* MERGEFORMATINET INCLUDEPICTURE "I:\\Biochemisy_2003 (G)\\dll\\cisretinal.jpg" \* MERGEFORMATINET All-trans-retinal11-cis-retinal
INCLUDEPICTURE "I:\\Biochemisy_2003 (G)\\dll\\retinol.jpg" \* MERGEFORMATINET INCLUDEPICTURE "I:\\Biochemisy_2003 (G)\\dll\\retinoic.jpg" \* MERGEFORMATINET RetinolRetinoic Acid
Each of these compounds are derived from the plant precursor molecule, Beta-carotene (a member of a family of molecules known as carotenoids). Beta-carotene, which consists of two molecules of retinal linked at their aldehyde ends, is also referred to as the provitamin form of vitamin A. however beta-carotene is not efficiently metabolized to vitamin A, beta-carotene is one-sixth as effective a source of vitamin A as retinol.
SHAPE \* MERGEFORMAT
Absorption and transport of vitamin A:
Gene Control Exerted by Retinol and Retinoic Acid (Mechanism of action of vitamin A):
Within cells both retinol and retinoic acid bind to specific receptor proteins. Following binding, the receptor-vitamin complex interacts with specific sequences in several genes involved in growth and differentiation and affects expression of these genes. In this capacity retinol and retinoic acid are considered hormones of the steroid and thyroid hormone superfamily of proteins. Vitamin D also acts in a similar capacity.-
-Functions of vitamin A:
1. Visual cycle (Vision and the Role of Vitamin A):
Vitamin A is a component of the visual pigments of rod and cone cells. Rhodopsin, the visual pigment of the rod cells in the retina, is necessary for vision in dim light. Rhodopsin consists of 11-cis retinal specifically bound to the protein opsin. When rhodopsin is exposed to light, a series of photochemical isomerizations occurs, which results in the bleaching of the visual pigment and release of all trans retinal and opsin. This process triggers a nerve impulse that is transmitted by the optic nerve to the brain. Regeneration of rhodopsin requires isomerization of all trans retinal back to 11-cis retinal. Trans-retinal, after being released from rhodopsin, is isomerized to 11-cis retinal, which spontaneously combines with opsin to form rhodopsin, thus completing the cycle.
11-cis retinal+opsin→rhodopsin light all transretinal+opsin
isomerization11-cis retinal
Rhodopsin is partly regenerated in the dark, the all trans-retinal, generated from rhodopsin by the absorption of light, is incompletely converted back to 11-cis-retinal. So in order to regenerate rhodopsin for vision , a constant supply of all-trans-retinal is required from diet.
2.Growth: Vitamin A deficiency results in a decreased growth rate in children. Bone development is also slowed.
3. Reproduction: Retinol and retinal are essential for normal reproduction. Retinoic acid is inactive in maintaining reproduction and in the visual cycle, but promote growth and differentiation of epithelial cells.
4. Maintenance of epithelial cells: Vitamin A is essential for normal differentiation of epithelial tissues and mucus secretion
Clinical Significances of Vitamin A Deficiency
Vitamin A is stored in the liver and deficiency of the vitamin occurs only after prolonged lack of dietary intake. Syntheses of retinol binding protein is reduced in response to infection decreasing the circulating concentration of the vitamin A and further impairing immune response.
The earliest symptoms of vitamin A deficiency are night blindness, which is poor vision in dim light.
Additional early symptoms include follicular hyperkeratinosis, increased susceptibility to infection and cancer .
Prolonged lack of vitamin A leads to deterioration of the eye tissue through progressive keratinization of the cornea, a condition known as xerophthalmia.
The increased risk of cancer in vitamin deficiency is thought to be the result of a depletion in beta-carotene. Beta-carotene is a very effective antioxidant and is suspected to reduce the risk of cancers known to be initiated by the production of free radicals. Of particular interest is the potential benefit of increased beta-carotene intake to reduce the risk of lung cancer in smokers. However, caution needs to be taken when increasing the intake of any of the lipid soluble vitamins. Excess accumulation of vitamin A in the liver can lead to toxicity.
Toxicity of retinoids:
Excessive intake of vitamin A lead to hypervitaminosis. Early sign: in skin :it become dry and pruritic, the liver enlarged and become cirrhotic, nausea and diarrhea, increased intracranial pressure and bone pain, it cause thickening of long bone, hypercalcaemia and calcification of soft tissues.Vitamin A should not be given in excess amount in pregnant because it cause congenital malformation in the developing fetus
Vitamin D
Vitamin D is consider as a steroid hormone that functions to regulate specific gene expression following interaction with its intracellular receptor. The biologically active form of the hormone is 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3, also termed calcitriol). Calcitriol functions primarily to regulate calcium and phosphorous homeostasis.
Distribution of vitamin D:
Diet: Ergocalciferol(vitamin D2), found in plants, cholecalciferol (vitamin D3), found in animal tissues, are sources of preformed vitamin D activity. Ergocalciferol and cholecalciferol differ chemically only in the presence of an additional double bond and methyl group in plant sterol.
endogenous vitamin precursor: 7-dehydrocholesterol, an intermediate in cholesterol synthesis, is converted to cholecalciferol in the dermis and epidermis of human exposed to sunlight.
INCLUDEPICTURE "I:\\Biochemisy_2003 (G)\\dll\\ergosterol.jpg" \* MERGEFORMATINET INCLUDEPICTURE "I:\\Biochemisy_2003 (G)\\dll\\vitamind2.jpg" \* MERGEFORMATINET ErgosterolVitamin D2
INCLUDEPICTURE "I:\\Biochemisy_2003 (G)\\dll\\7dehydrocholesterol.jpg" \* MERGEFORMATINET INCLUDEPICTURE "I:\\Biochemisy_2003 (G)\\dll\\vitamind3.jpg" \* MERGEFORMATINET 7-DehydrocholesterolVitamin D3So..Exposure to Sun and Then, Fortified Foods.Give Us the D We Need
Metabolism of vitamin D:
Active calcitriol is derived from ergosterol (produced in plants) and from 7-dehydrocholesterol (produced in the skin). Ergocalciferol (vitamin D2) is formed by uv irradiation of ergosterol. In the skin 7-dehydrocholesterol is converted to cholecalciferol (vitamin D3) following uv irradiation.Vitamin D2 and D3 are processed to D2-calcitriol and D3-calcitriol, respectively, by the same enzymatic pathways in the body. Cholecalciferol (or egrocalciferol) are absorbed from the intestine and transported to the liver bound to a specific vitamin D-binding protein. In the liver cholecalciferol is hydroxylated at the 25 position by a specific D3-25-hydroxylase generating 25-hydroxy-D3 [25-(OH)D3] which is the major circulating form of vitamin D. Conversion of 25-(OH)D3 to its biologically active form, calcitriol, occurs through the activity of a specific D3-1-hydroxylase present in the proximal convoluted tubules of the kidneys, and in bone and placenta. 25-(OH)D3 can also be hydroxylated at the 24 position by a specific D3-24-hydroxylase in the kidneys, intestine, placenta and cartilage.
INCLUDEPICTURE "I:\\Biochemisy_2003 (G)\\dll\\25hydroxyvitamind3.jpg" \* MERGEFORMATINET INCLUDEPICTURE "I:\\Biochemisy_2003 (G)\\dll\\1_25dihydroxyvitamind3.jpg" \* MERGEFORMATINET 25-hydroxyvitamin D31,25-dihydroxyvitamin D3the activity of 1-hydroxylase is increased directly by low plasma phosphate or indirectly by low plasma calcium, which triggers the release of PTH. Hypocalcemia caused by insufficient dietary calcium thus results in elevatedlevels of plasma 1,25 (OH)2 vit D.
SHAPE \* MERGEFORMAT
Function of vitamin D:Effect of vitamin D on intestine: In the intestinal epithelium, calcitriol functions as a steroid hormone in inducing the expression of calbindin, a protein involved in intestinal calcium absorption. The increased absorption of calcium ions requires concomitant absorption of a negatively charged counter ion to maintain electrical neutrality. The predominant counter ion is Pi.
SHAPE \* MERGEFORMAT SHAPE \* MERGEFORMAT
Shows Expressed Calbindins and How the facilitate transport of Calcium through the Membranes
Calcium absorption is transport across the epithelial cell, which is greatly enhanced by the carrier protein calbindin, the synthesis of which is totally dependent on vitamin D
Distribution and requirement of vitamin D:
Vitamin D occur naturally in fatty fish, liver, and egg yolk. Milk, unless it is artificially fortified, is not good source of vitamin D.Clinical Significance of Vitamin D Deficiency
The main symptom of vitamin D deficiency in children is rickets and in adults is osteomalacia.
These patients have:
1.Bone pain
2. Local tenderness
3. May have proximal myopathy
4. Skeletal deformity may be present particularly in rickets.
Rickets is characterized improper mineralization during the development of the bones resulting in soft bones. Osteomalacia is characterized by demineralization of previously formed bone leading to increased softness and susceptibility to fracture. Toxicity of vitamin D
Vitamin D is the most toxic of all vitamins, as it can be stored in the body and slowly metabolised.
High doses can cause: loss of appetite, nausea, thirst, enhanced calcium absorption and bone resorption result in hypercalcemia
Summary:
Vitamin A consists of three biologically active molecules,retinol, retinal and retinoic acid.
Functions of vitamin A: Visual cycle, Growth, Reproduction, Maintenance of epithelial cells.
vitamin A deficiency are night blindness, hyperkeratinosis, xerophthalmia
Beta-carotene is a very effective antioxidant and is suspected to reduce the risk of cancers
Vitamin D is consider as a steroid hormone
. The biologically active form of the hormone is 1,25-dihydroxy vit. D3
The main symptom of vitamin D deficiency in children is rickets and in adults is osteomalacia.