Overview of Vitamin-D: its chemistry, sources, metabolism, functions, and deficiency

Overview of Vitamin-D

     Vitamin D is a fat-soluble vitamin. It has a resemblance with sterol. It is also called Sunshine Vitamin. This vitamin is now termed as a Prohormone. Vitamin D has two major forms named Vitamin D2 and Vitamin D3.

     Vitamin D2 is found in plants and it is man-made and added to foods then. This vitamin is also called Ergocalciferol. While the other, Vitamin D3(cholecalciferol) is synthesized in the skin by the action of UV-blue rays on 7-dehydrocholesterol.

     The cholecalciferol and ergocalciferol, both are provitamins, while the active form of vitamin-d is Calcitriol (1,25-dihydroxycholecalciferol). The Vitamin D normal range is about 9-11 mg/dl.

Chemistry of Vitamin D

     The active form of Vitamin D is synthesized from Cholecalciferol. During the synthesis of cholesterol, an intermediate, called 7-dehydrocholesterol, is formed, that is present in the epidermis of the skin.

     First, the compound present in the epidermis of the skin, 7-dehydrocholesterol, is converted to cholecalciferol by the action of UV-blue rays of sunlight. Dark stain pigments (Melanin) adversely influence the synthesis of Cholecalciferol.

     Cholecalciferol will move to the liver, where the enzyme 25-hydroxylase along with NADPH, O2, and Cytochrome P450 complex converts the Cholecalciferol into 25-hydroxycholecalciferol. 

     The 25-hydroxycholecalciferol will move to the kidney, where an enzyme named 1-alpha-hydroxylase, converts it into an active form of Vitamin D that is Calcitriol (1,25-dihydroxycholecalciferol). 

     Both sterols, Ergocalciferol and Cholecalciferol have the same structures, but the difference is that Ergocalciferol has an additional methyl group and a double bond. Both are the sources of Vitamin D activity, that's why called Provitamins.

Vitamin D Sources

     There are different vitamin d sources, that are given below:

• The major source of Vitamin d is the exposure of the body to sunlight.
• Other sources of vitamin d include fatty fish, fish liver oil, and egg yolk.
• Milk is also a source of vitamin d, but a moderate source.

Vitamin D daily requirements

     The recommended daily allowance (RDA) of vitamin d is given below for different conditions:

• For a child, the recommended requirement is about 400 IU (International Unit) or 10 mg.
• For an adult, the daily requirement is 200 IU or 5 mg
• For pregnant or lactating women, the daily requirement is 400 IU or 10mg.
• For an individual more than 60 years of age, the requirement is 600 IU or 15 mg.

Regulation of active form of Vitamin D synthesis

     The concentration of 1,25-dihydroxycholecalciferol (the active form of vitamin-d) is regulated by the plasma levels of Calcium and Phosphate. The decrease in the plasma level of phosphate leads to the elevation of the activity of 25-hydroxycholecalciferol 1-hydroxylase. And the decrease in the plasma level of calcium leads to increase production of parathyroid hormone, which ultimately activates the 1-hydroxylase.

     So, the action of Calcium is indirect on 1-hydroxylase, unlike the action of phosphate on 1-hydrolase.

                                  

Vitamin D active form

     The active form of Vitamin D is 1,25-dihydroxycholecalciferol, which is also called Calcitriol. While Ergocalciferol and Cholecalciferol are the Provitamins. The vitamin d, that can be stored and transported, is the 25-dehydroxycholecalciferol.

Vitamin D is a hormone, not a vitamin (Justification)

     Calcitriol is termed as an important calciotropic hormone while Cholecalciferol is a prohormone.Following are the justifications that Vitamin d is a hormone, not a vitamin.

• Vitamin-D3 is synthesized in the skin by the action of UV-blue rays on 7-dehydrocholesterol.
• The biologically active form of Vitamin D, 1,25-dihydroxycholecalciferol, is produced in the kidney.
• Vitamin D has the target organs where it specifically acts.
• The action of vitamin d is similar to a steroid hormone, as it binds to a receptor in the cytosol, and forms a complex, that then acts on DNA and forms a Calcium Binding Proteins (CBP).
• Actinomycin D inhibits Calcitriol, as it supports a view that calcitriol exerts an effect on DNA for the synthesis of RNA.
• The synthesis of Calcitriol is self-regulated by the feedback mechanism, that calcitriol decreases its own synthesis.

     All of these points reveal that Vitamin D is not a vitamin, but it is a hormone.

Vitamin D functions

     The important role of vitamin d is to regulate the levels of calcium and phosphate. The action of Vitamin D is on the tissues of the target organs. These target organs include Bone, Intestine, and Kidney.

     In intestine target cells, vitamin d increases the production of Calcium-binding proteins by acting through Intracellular receptors. It also increases intestinal absorption of calcium and phosphate.

     In the kidney target tissues, vitamin d acts on renal tubules and increases the reabsorption of calcium and phosphate from the renal tubules. When calcitriol level is adequate, the kidney leads to the formation of 24,25-dihydroxycholecalciferol by the action of enzyme 24-hydroxylase, present in kidney, on 25-hydroxycholecalciferol. The function of this compound is still unknown, but its synthesis is important for the maintenance of homeostasis of Calcium.

     In the bone target tissues, vitamin d is responsible for the formation of bones, called the Remodeling of bones. Vitamin d also acts on Osteoblastic activity. It increases the mineralization of bones results in the deposition of calcium and phosphate. Calcitriol along with parathyroid hormone increases the mobilization of calcium and phosphate of bone, which leads to an increase of calcium and phosphate levels of plasma.

     Vitamin d is helpful in the treatment of Psoriasis because it has antiproliferative action. It also has immunomodulatory functions. Vitamin d is also useful for the prevention of coronary artery disease, and also useful for some cancers.

Vitamin d deficiency

     The deficiency of Vitamin d is less common, but insufficient exposure to sunlight and strict vegetarians, Alcoholic individuals, Individuals having either Liver or kidney disease, or fat malabsorption syndrome may lead to Vitamin D deficiency.

     The deficiency of Vitamin d leads to Rickets in children, Osteomalacia in adults, Renal rickets also called Renal Osteodystrophy, and Vitamin d resistant rickets. All of these are explained below:

• Rickets: This condition occurs in children. The first symptom below 2 years of age is Craniotabes means soft and pliable skull bones due to defective mineralization. Other symptoms include delayed closure of fontanelles, frontal bossing, widening of epiphysis or wrist mainly involves radius and ulna, bowed legs, Rachitic rosary, and Harrison's Sulcus (means there is a transverse groove along with the insertion of the diaphragm).
• Osteomalacia: This condition mostly occurs in adults. In this condition, the demineralization of bones occurs, which leads to softening of the bone. Individuals having this condition may have easy fractures. Patients with Osteomalacia may have a disorder named Osteoporosis in which the bones become porous. 
• Renal Rickets: This disease is also called Renal Osteodystrophy. it occurs due to defective conversion of Vitamin d, thus an active form of vitamin D is absent.
• Vitamin D Resistant Rickets: It occurs due to defective renal tubule absorption.