1.

2. Calcitriol
Muhammad Shahzeb
Roll # 177
3. Layout:
Introduction
Biosynthesis and regulation
Transport
Mechanism of action
Metabolism
Metabolic Actions
Abnormalities associated with calcitriol
- Hypovitamenosis D
- Hypervitamenosis D
4. Introduction:
Calcitriol also called 1,25-dihydroxycholecalciferol,
active form of vitamin D with three alcohol groups
It increases the level of calcium (Ca2+) in the blood
5. Biosynthesis and its regulation:
Produced in the cells of the proximal tubule of the nephron
By the action of 25-hydroxyvitamin D3 1-alpha-hydroxylase
The activity of the enzyme is stimulated by
- PTH.
- Prolactin
- Decreased levels of serum phosphate
6. skin
7-dehydro cholesterol
Previtamin D3
Vitamin D3
25-hydroxylase
liver
25-hydroxycholcalciferol
25 hydroxycolcalciferol 1-hydroxylase
kidney
1,25-dihydroxycol calciferol
7. 8. Transport:
Vitamin D-binding protein belongs to the albuminfamily
458 amino acids
Codedby 1690 nucleotides on chromosome 4
Found in
-plasma,
-cerebrospinal fluid
-on the surface of many cell types
It binds to vitamin D and its plasma metabolites and transports them to target tissues
9. Mechanism of action:
10. Metabolism:
Half life - approx. 5-8 hours.
This enzyme plays a role in calcium homeostasis and of calcitriol
24-hydroxylase
calcitriol
Calcitric
acid
11. Metabolic Actions
12. 13. Intestinal Ca+2 absorption:
Increases the absorption of Ca
Increases the production of Calmodulin (CaBP).
14. On bones:
Type 1 Collagen
osteoclastin
Osteoblasts Osteoclast
absorption of Cain bones
15. 16. Action on kidneys
A major action of calcitriol is to regulate renal 25-hydroxyvitamin D,-1-hydroxylase
It has been shown that calcitriol brings about a suppression of this enzyme
Thus it helps to regulate the formation of calcitriol by negative feedback inhibition.
17. On skeletal and cardiac muscles
the rate of Ca uptake by sarcoplasmic reticulum of skeletal muscles
skeletal muscle mass
Can cause the calcification of cardiac muscle
Lead to myocardial failure
18. On cancer cells:
Cancerous cells have receptors for calcitriol
Calcitriol represses the cell proliferation
So it along with its analogs can be use for treating the cancer
19. On skin:
melanin synthesis.
preventing the skin penetration of sunlight.
7-dehydrocholesterol is not converted to pre-vitamin D
Feedback regulation.
20. Endocrine functions:
Parathyroid Gland:
Inhibits the proliferation of parathyroid cells
Inhibits the parathyroid genes form transcription
Thus can be used to treat hyper-parathyroidism.
Pituitary gland
Increases prolactin synthesis and secretion from pituitary cells.
21. Pancreas:
vitamin D deficiency inhibited insulin secretion from thepancreas, whereas vitamin D repletion improved insulin secretion
22. Disorders related to calcitriol:
Vitamin D deficiency:
Type I:
Type II:
Body is unable to utilize vitamin D due to defect in the receptor of calcitriol.
hydroxylase
25,OH D3
calcitriol
23. Diseases related to vitamin D deficiency
Rickets
- Softening of bones in children potentially leading to fractures and deformity in bones

The predominant cause is a vitamin Ddeficiency

Sign & symptoms:
Bone pain or tenderness
dental problems
muscle weakness
Growth disturbance
Hypocalcemia
Tetany
24. Treatment and prevention:
Increase dietary intake of calcium, phosphates and vitamin D.
Exposure to sunlight
cod liver oil
25. Osteomalacia
Osteomalacia is the softening of the bones due to defective bone mineralization
Signs and Symptoms
Weak bones
Bone pain
Muscle weakness
Hypocalcemia
Compressed vertebrae
Fractures
Bone softening
Bending of bones
Pain
26. Treatment
Oral administration of vitamin D.
Osteomalaciadue to malabsorption may require treatment by injection of significant amounts of vitamin D.
27. Hypervitaminosis D
Is tolerable
But deleterious in extreme large dosage 500-1000 times than normal
Effects:
Immediate effects:
Anorexia
Thirst
Lassitude(fatigue)
Constipation
Polyuria
Nausea
Vomiting
Diarrhoea
28. Delayed effects: persistent hypercalcemia and hyperphospatemia may result
Urinary lithasis
Metastatic calcification
Effecting

Kidneys

29. Bronchi 30. Arteries 31. Muscles