(Vitamin D3 (Cholecalciferol

Vitamin D3 (Cholecalciferol)
“Anti-rickets vitamin, anti-osteomalacia vitamin”.
Chemistry
7-dehydrocholesterol is the precursor (provitamin) of vitamin D3 (Cholecalciferol). It is present in subcutaneous fats.
Synthesis of vitamin D3 from 7 dehydrocholesterol requires exposure to sun light, rather than dietary supply. Vitamin D3 is considered an atypical vitamin since it can be synthesized inside our body. It is a vitamin that depends on sunshine “sunshine vitamin”

Sources:
Provitamins: They give vitamin D2 and D3 by ultraviolet rays.
Ergosterol (provitamin D2): widely distributed in plants especially yeast.
7-dehydrocholesterol (endogenous source of vitamin D3): in animals only. It is formed by intestinal mucosa from cholesterol and passes to the circulation to become subcutaneous. Thus, exposure to sunlight is essential for formation of vitamin D3.
Sources of vitamin D3 itself:
Cod liver oil, tuna liver oil, egg yolk, butter. Milk is a poor source of vitamin D3.
Activation of vitamin D3 (cholecalciferol):
First hydroxylation reaction in the
liver by microsomal hydroxylase
It adds OH at position 25 to form
25 hydroxycholecalciferol
(25-OH D3, 25-OH-CC).
Second hydroxylation reaction occurs in the kidney.
The renal mitochondrial Hydroxylase enzyme adds a OH to either position 1 or position 24 depending upon the blood calcium level.
In case of low calcium levels (hypocalcemia), there is a high level of parathyroid hormone. It stimulates hydroxylation at position 1, therefore, 1,25 Dihydroxy cholecalciferol (1,25 DHCC) is synthesized.
1,25 DHCC is the more potent than 24,25 DHCC. 1,25 DHCC is also termed Calcitriol since it contains three hydroxyl groups at 1, 3 and 25 positions.

Functions of activated vitamin D3:
The main function of 1,25 di OH CC is to maintain normal plasma calcium
levels. It performs this function by:
Increasing uptake of calcium by the intestine. 1,25 dihydroxycholecalciferol acts a steroid hormone. It enters the intestinal cells where it binds to a specific cytosolic receptor. Calcitriol receptor complex then binds to a specific DNA sequence stimulating the expression of a specific gene that encodes the synthesis of calcium binding protein termed calbindin.
Minimizing loss of calcium by the kidney
Stimulating resorption of bone when necessary. It stimulates osteoblasts, which secrete alkaline phosphatase. Alkaline phosphatase enzyme increases deposition of phosphate and subsequent bone mineralization. 1,25 di OH CC stimulates the mobilization of calcium and phosphorus from bone in the presence of PTH.
Deficiency of vitamin D:
Causes:
Decreased intake with improper exposure to sunshine.
Decreased absorption as in case of obstructive jaundice.
Decreased activation as in case of liver and kidney diseases.
Failure of binding between activated vitamin D3 and its receptor.
Manifestations of deficiency:
I- In adults: Osteomalacia, characterized by bone softening due to defective mineralization. Osteomalacia is more common in women with multiple pregnancies and bad eating habits.
Osteomalacia is manifested by:
Bone deformities.
Bone pain and aches.
Easily fractured bones with delayed healing.
II- In young growing children: Rickets, characterized by:
Softening and deformities of bones
Delayed teething, standing and walking.
Bow legs, bossing of frontal bones, pigeon chest, and rickety rosary due to enlargement of the costochondral junction.
Vitamin D resistant rickets:
Patients with kidney disease will suffer from vitamin D resistant rickets. They can not activate available vitamin D. They are treated by administration of activated vitamin D (Calcitriol).
Biochemical changes in vitamin D deficiency:
Decreased serum phosphate levels.
Mild decrease in serum calcium levels only in severe cases.
Increased levels of serum alkaline phosphatase (bone isoenzyme).
Toxicity (Hypervitaminosis D):
Vitamin D is the most toxic of all vitamins.
It is characterized by hypercalcemia. Calcium is deposited in bones and soft tissues causes metastatic calcification.
It causes premature closure of sutures and fontanels in
children leading to microcephaly. Calcification of kidney tissue
(nephrocalcinosis) may lead to renal failure.