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BY : VAIBHAV MITTAL
Vitamin-D is a fat soluble vitamin
Vitamin – D is a sterol, it contains steroid nucleus
(Cyclopentanoperhydrophenanthrene ring)
Vitamin – D function like a hormone
Forms of vitamin D:
Vitamin D in the diet occurs in two forms
Vitamin D2 (Ergocalciferol)
Vitamin D3 (Cholecalciferol)
Ergocalciferol (vitamin D2) is formed from
ergosterol and is present in plants
CH3
Cholecalciferol (vitamin D3) is found in
animals
Both the sterols are similar in structure
except that ergocalciferol has an additional
methyl group and a double bond
Ergocalciferol and Cholecalciferol are
sources for vitamin D activity and are
referred as provitamins
During the course of cholesterol
biosynthesis 7-dehydrocholesterol is formed
as an intermediate
On exposure to sunlight, 7-
dehydrocholesterol is converted to
cholecalciferol in the skin (dermis and
epidermis)
Dark skin pigment (melanin) adversely
influences the synthesis of cholecalciferol
Skin is the largest organ in the body
The production of vitamin D in the skin is
directly proportional to the exposure to
sunlight and inversely proportional to the
pigmentation of skin
Excessive exposure to sunlight does not
result in vitamin D toxicity since excess
provitamin D3 are destroyed by sunlight
itself
Diet from animal sources such as animal liver
contains vitamin D3
Diet from plant sources contains vitamin D2
Absorption: vitamin D2 and D3 are absorbed
from upper small intestine and bile is essential
Mechanism: vitamin D3 and D2 form mixed
micelles by combining with bile salts
(micelles)
Mixed micelles are presented to mucosal cells
Absorption occurs by passive transport
Vitamin D binding globulin: vitamin D is
transported from intestine to the liver by
binding to vitamin D binding globulin
25 – Hydroxy D3 and 1,25 – dihydroxy D3 are
also transported in the blood by binding to
vitamin D binding globulin
Storage:
25 – hydroxycholecalciferol is the major
storage and circulatory form of vitamin D
Synthesis of 1,25 –Synthesis of 1,25 –
Dihydroxycholecalciferol:Dihydroxycholecalciferol:
Active form: the active form of vitamin D is
1,25 – Dihydroxycholecalciferol and is also
called as calcitriol
Cholecalciferol is first hydroxylated at 25th
position to 25 – hydroxycholecalciferol by a
specific hydroxylase present in liver
Kidney possesses a specific enzyme, 25 –
hydroxycholecalciferol 1 – hydroxylase
25 – hydroxycholecalciferol 1 – hydroxylase
hydroxylates 25 – hydroxycholecalciferol at
position 1 to produce 1,25 –
Dihydroxycholecalciferol (1,25-DHCC)
1,25 – DHCC contains 3 hydroxyl groups (1,
3, 25) and called as calcitriol
Both hydroxylase enzymes (of liver and
kidney) require cytochrome P450, NADPH
and molecular oxygen for hydroxylation
process
Formation of 1,25 – DHCC is regulated by the
regulation of renal 1 α – hydroxylase
1 α – hydroxylase activity is increased by
hypocalcemia
Hypocalcemia stimulates PTH secretion
which, in turn, increases 1 α – hydroxylase
1 α – hydroxylase activity may be feedback
inhibited by 1,25 – DHCC

In chronic renal failure, 1 α – hydroxylase
activity is decreased leading to decreased
synthesis of 1,25 – DHCC
The condition leads to renal osteodystrophy
(renal rickets)
Condition is treated by giving 1,25 – DHCC
preparations
1 α – hydroxylase deficiency can also occurs
as inherited disorder or due to
hypoparathyroidism
Vitamin D regulates the plasma levels of
calcium and phosphorous
Plasma calcium levels are regulated by
effects of 1,25 – DHCC on small intestine,
kidney and bone
It maintains the plasma calcium levels by
increasing absorption of calcium from small
intestine, increasing reabsorption of
calcium by renal distal tubules and
increasing mobilization of calcium from bone
Calcitriol (1,25 – DHCC) acts at three
different levels to maintain plasma calcium
Action on intestine:
Calcitriol increases the intestinal absorption
of calcium and phosphate
In the intestinal cells, calcitriol binds with a
cytosolic receptor to form a calcitriol-
receptor complex
This complex interacts with a specific DNA
leading to the synthesis of a specific calcium
binding protein
This protein increases calcium uptake by
intestine
 The mechanism of action of calcitriol is
similar to that of steroid hormone
Action on bone:
In osteoblasts of bone, calcitriol stimulates
calcium uptake for deposition as calcium
phosphate
Calcitriol is essential for bone formation
Calcitriol along with parathyroid hormone
increases the mobilization of calcium and
phosphate from the bone
Causes elevation in the plasma calcium and
phosphate
Action on kidney:
Calcitriol is also involved in minimizing the
excretion of calcium and phosphate through
the kidney by decreasing their excretion and
enhancing reabsorption
24,25 – DHCC is another metabolite of
vitamin D
It is synthesized in kidney by 24 -
hydroxylase
Calcitriol concentration is adequate, 24 –
hydroxylase acts leading to the synthesis of
a less important compound 24,25 – DHCC
To maintain calcium homeostasis, synthesis
of 24,25 – DHCC is important
Children - 10 gm/day or 400 IU/day
Adults - 5 gm/day or 200 IU/day
Pregnency,lactation -10 gm/day or 400 IU/day
Above the age of 60 yrs - 600 IU /day
Sources of vitamin D:
Exposure to sunlight produces cholecalciferol
Good sources includes – fatty fish, fish liver
oils, egg yolk etc
Milk is not a good source

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Vitamin d metabolism

  • 1. BY : VAIBHAV MITTAL
  • 2. Vitamin-D is a fat soluble vitamin Vitamin – D is a sterol, it contains steroid nucleus (Cyclopentanoperhydrophenanthrene ring) Vitamin – D function like a hormone Forms of vitamin D: Vitamin D in the diet occurs in two forms Vitamin D2 (Ergocalciferol) Vitamin D3 (Cholecalciferol)
  • 3. Ergocalciferol (vitamin D2) is formed from ergosterol and is present in plants CH3
  • 4. Cholecalciferol (vitamin D3) is found in animals Both the sterols are similar in structure except that ergocalciferol has an additional methyl group and a double bond Ergocalciferol and Cholecalciferol are sources for vitamin D activity and are referred as provitamins
  • 5. During the course of cholesterol biosynthesis 7-dehydrocholesterol is formed as an intermediate On exposure to sunlight, 7- dehydrocholesterol is converted to cholecalciferol in the skin (dermis and epidermis) Dark skin pigment (melanin) adversely influences the synthesis of cholecalciferol
  • 6. Skin is the largest organ in the body The production of vitamin D in the skin is directly proportional to the exposure to sunlight and inversely proportional to the pigmentation of skin Excessive exposure to sunlight does not result in vitamin D toxicity since excess provitamin D3 are destroyed by sunlight itself
  • 7.
  • 8. Diet from animal sources such as animal liver contains vitamin D3 Diet from plant sources contains vitamin D2 Absorption: vitamin D2 and D3 are absorbed from upper small intestine and bile is essential Mechanism: vitamin D3 and D2 form mixed micelles by combining with bile salts (micelles) Mixed micelles are presented to mucosal cells Absorption occurs by passive transport
  • 9. Vitamin D binding globulin: vitamin D is transported from intestine to the liver by binding to vitamin D binding globulin 25 – Hydroxy D3 and 1,25 – dihydroxy D3 are also transported in the blood by binding to vitamin D binding globulin Storage: 25 – hydroxycholecalciferol is the major storage and circulatory form of vitamin D
  • 10. Synthesis of 1,25 –Synthesis of 1,25 – Dihydroxycholecalciferol:Dihydroxycholecalciferol: Active form: the active form of vitamin D is 1,25 – Dihydroxycholecalciferol and is also called as calcitriol Cholecalciferol is first hydroxylated at 25th position to 25 – hydroxycholecalciferol by a specific hydroxylase present in liver Kidney possesses a specific enzyme, 25 – hydroxycholecalciferol 1 – hydroxylase
  • 11. 25 – hydroxycholecalciferol 1 – hydroxylase hydroxylates 25 – hydroxycholecalciferol at position 1 to produce 1,25 – Dihydroxycholecalciferol (1,25-DHCC) 1,25 – DHCC contains 3 hydroxyl groups (1, 3, 25) and called as calcitriol Both hydroxylase enzymes (of liver and kidney) require cytochrome P450, NADPH and molecular oxygen for hydroxylation process
  • 12. Formation of 1,25 – DHCC is regulated by the regulation of renal 1 α – hydroxylase 1 α – hydroxylase activity is increased by hypocalcemia Hypocalcemia stimulates PTH secretion which, in turn, increases 1 α – hydroxylase 1 α – hydroxylase activity may be feedback inhibited by 1,25 – DHCC 
  • 13. In chronic renal failure, 1 α – hydroxylase activity is decreased leading to decreased synthesis of 1,25 – DHCC The condition leads to renal osteodystrophy (renal rickets) Condition is treated by giving 1,25 – DHCC preparations 1 α – hydroxylase deficiency can also occurs as inherited disorder or due to hypoparathyroidism
  • 14. Vitamin D regulates the plasma levels of calcium and phosphorous Plasma calcium levels are regulated by effects of 1,25 – DHCC on small intestine, kidney and bone It maintains the plasma calcium levels by increasing absorption of calcium from small intestine, increasing reabsorption of calcium by renal distal tubules and increasing mobilization of calcium from bone
  • 15. Calcitriol (1,25 – DHCC) acts at three different levels to maintain plasma calcium Action on intestine: Calcitriol increases the intestinal absorption of calcium and phosphate In the intestinal cells, calcitriol binds with a cytosolic receptor to form a calcitriol- receptor complex
  • 16. This complex interacts with a specific DNA leading to the synthesis of a specific calcium binding protein This protein increases calcium uptake by intestine  The mechanism of action of calcitriol is similar to that of steroid hormone Action on bone: In osteoblasts of bone, calcitriol stimulates calcium uptake for deposition as calcium phosphate
  • 17. Calcitriol is essential for bone formation Calcitriol along with parathyroid hormone increases the mobilization of calcium and phosphate from the bone Causes elevation in the plasma calcium and phosphate Action on kidney: Calcitriol is also involved in minimizing the excretion of calcium and phosphate through the kidney by decreasing their excretion and enhancing reabsorption
  • 18. 24,25 – DHCC is another metabolite of vitamin D It is synthesized in kidney by 24 - hydroxylase Calcitriol concentration is adequate, 24 – hydroxylase acts leading to the synthesis of a less important compound 24,25 – DHCC To maintain calcium homeostasis, synthesis of 24,25 – DHCC is important
  • 19.
  • 20.
  • 21. Children - 10 gm/day or 400 IU/day Adults - 5 gm/day or 200 IU/day Pregnency,lactation -10 gm/day or 400 IU/day Above the age of 60 yrs - 600 IU /day Sources of vitamin D: Exposure to sunlight produces cholecalciferol Good sources includes – fatty fish, fish liver oils, egg yolk etc Milk is not a good source