Synthesis of Vitamin D in Skin, transport and metabolism:

Transport and metabolism of calcitriol:

• The active form of Vit-D is calcitriol (1,25-dihydroxy cholecalciferol).
• The liver enzyme cholecalciferol-25-hydroxylase synthesize 25-hydrocholecalciferol from cholecalciferol.
• 25-hydrocholecalciferol is also termed as Calcidiol.
• Placenta also consists of the enzyme 25-hydroxycholecalciferol-1-hydroxylase.
• In kidney, when calcitriol is adequate, an enzyme 24-hydroxylase stores calcitriol in the form of 24,25-dihydroxy cholecalciferol.
• 24,25- dihydroxycholecalciferol also significantly contribute to maintain phosphorus and calcium homeostasis.

Regulation of blood calcium level by calcitriol:

• Plasma level of calcium and phosphorus regulate the activity of calcitriol formation which in turn maintains the calcium level of plasma.

Biological role of Vitamin D:

• The major function of vitamin D is to maintain the plasma level of calcium and phosphorus.
• Calcitriol functions by acting on three major sites:

i. Action in intestine:

• Vitamin D (Calcitriol) stimulate the calcium absorption in the intestine.
• Calcitriol in intestinal cells bind to the calcitriol receptor forming calcitriol receptor complex.
• This calcitriol acts on nucleus stimulating the DNA to produce mRNA and therefore protein called calcium binding protein.
• This calcium binding protein binds and absorbs the calcium.

ii. Action in bone:

• Calcium is very essential for bone formation.
• Calcitriol stimulates calcium absorption and deposition as calcium phosphate.
• Calcium along with parathyroid hormone mobilizes the calcium and phosphate from bone.

iii. Action in kidney:

• Calcitriol along with parathyroid hormone inhibits the calcium excretion from kidney, meanwhile, calcitriol also stimulates the reabsorption of calcium from renal tubules.

Steroid hormone like activity of Vitamin D:

• Vitamin D acts like a steroid hormone, calcitriol stimulates DNA and synthesizes calcium binding protein is intestinal cells.
• Similar to hormones, Vitamin D has short half-life of about 10 hours.
• Biologically active form of vitamin D calcitriol, like steroid hormones is synthesized in kidney.
• Calcitriol is synthesized in skin upon exposure to sunlight.
• Vitamin-D acts along with other hormones like parathyroid hormone and calcitonin to regulate the plasma level of calcium.
• Vitamin-D acts on DNA and is associated with the activation of transcription. This can be justified in a fact that vitamin D is inhibited by actinomycin D. Actinomycin D inhibits initiation of transcription.
• Vitamin D, like hormones have specific organs of action. They act on bone, kidney and intestine.
• Vitamin D (calcitriol) synthesis is subjected to feedback control mechanism like hormones. Calcitriol decreases its own synthesis.

RDA of vitamin D:

• The recommended dietary allowance (RDA) varies from 5 μg/day (in countries with high exposure to sunlight) to 10 μg/day.

Dietary sources of vitamin D:

• Fatty fish, fish liver oil, egg yolk
• vitamin D is also obtained by consumption of irradiated food (irradiated yeast) and exposure to sunlight.

Vitamin D deficiency:

• Vitamin D deficiency occur due to inadequate exposure to sunlight and inadequate consumption of Vitamin D diet.
• Vitamin D deficiency occurs in strict vegetarians, chronic alcoholic, liver and kidney disease and mal-absorption.
• Deficiency results in rickets in children, a condition that is characterized by incomplete mineralization that result in soft and pliable bone and delay in teeth formation.
• In adults deficiency leads to osteomalacia, a condition involving softening of bone.
• This results from bone demineralization.
• Bones are highly susceptible for fracture.
• Renal rickets can occur in individual with renal failure due to decreased synthesis of calcitriol.

Hypervitaminosis D:

• Excessive vitamin D at more than rate 100 times required RDA results in hypervitaminosis of Vitamin D.
• Excessive vitamin D can result in nausea, loss of appetite, loss of body weight.

Vitamin D: Synthesis, regulation, biological roles, sources and deficiency

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