36 - Vitamin D3 Receptors Flashcards
Vitamin D3 (where is It produced and released?)
o Vitamin D3 (cholecalciferol) is produced in the skin by the action of ultraviolet light on 7-dehydrocholesterol
o It is released into the plasma and passes to the liver, where it is converted into 25-hydroxycholecalciferol
o This then passes to the proximal convoluted tubule in the kidney where a further hydroxyl group is added to produce 1,25-dihydroxycholecalciferol (1,25-(OH)2D3; also called calcitriol) by an enzyme found on the mitochondrial inner wall
What is the regular cholesterol we get in our diet?
7-dehydrocholeserol is a regular cholesterol that can get in our diet
o UV light acts on this to make the pre-vitamin D3 in the skin
o This opens further to make vitamin D3
Where is vitamin D3 converted?
o Vitamin D3 is converted in the liver to 25 hydroxy called calciferol which lasts quite a long time
o In the kidney this is switched on further by adding another hydroxyl to make 1, 25 hydroxyl
Control of calcium and phosphate homeostasis
Overview of the hormonal control of calcium and phosphate homeostasis by parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25-(OH)2D)
What is broken down?
he bone material which is made of calcium phosphates broken down by osteoclast cells
What does vitamin D potentiate?
Vitamin D potentiates the actions of parathyroid hormone
What happens in the kidney?
In the kidney we get reabsorption of calcium and excretion of phosphate, regulated by parathyroid hormone
o This is also facilitated by vitamin D3
o Vitamin D3 causes absorption of calcium from the gut, so we have parathyroid hormone causing calcium absorption from the kidney and also causing absorption from the gut
What is the key step for vitamin D3 regulated by?
They key activating step for vitamin D3 is regulated by parathyroid hormone, which regulates the activation of hydroxylase enzyme in the mitochondria of kidney cells
o This causes the switch of 25 hydroxy vitamin D3 to 1,25 dihydroxy vitamin D3 which can now act on the gut and on the bone to increase calcium levels
Why do the actions of 1,25-(OH)2D3 occur?
The actions of 1,25-(OH)2D3 occur as a consequence of binding to DNA and increasing transcription of mRNAs
Vitamin D3 has the following properties:
- It is essential for bone development and also for demineralisation and release of Ca2+ and Po4(3-)
- It stimulates renal tubular reabsorption; a specific 1,25-(OH)2D3 receptor has been identified in the kidney in the distal convoluted tubules of the nephrons
- It causes reabsorption from the intestine and transports PO4(3-) across the gut epithelium as an active transport mechanism\
- Transport within the intestinal epithelium is achieved by stimulating Ca2+ entry into the epithelial cells
What do all transport mechanisms require?
All transport mechanisms require calcium-binding proteins (ca-BPs), the synthesis of which is increased by vitamin D
What does the vitamin D3 receptor cause?
o Vitamin D3 receptor causes transcription of a gene coding for calcium binding protein or calcium Bps
o These are synthesised in the gut by vitamin D3 acting on this receptor
Number of ways with which calcium can be brought up:
o Calcium can be absorbed in the gut and interact directly with calcium binding protein and then can be further absorbed into the body in exchange for sodium
o Calcium binding protein can allow calcium to be transported between epithelial cells into the body
- This is called transcellular transport
o Calcium binding protein cause vesicular storage of calcium
o Simple calcium channel which allows calcium uptake
