IMMUNITY

Vitamin D – Synthesis and Roles in the Body

This is a brief overview of how Vitamin D is synthesised in the body, how it acts on the vitamin D receptor and what effects it has on the body.

Vitamin D can be made in the skin when it’s exposed to sunlight. First cholesterol is turned into 7 dehydrocholesterol by an enzyme called dhcr7. UVB radiation from the sun, then turns this into previtamin D, which spontaneously transforms into vitamin D at body temperature. This actually means that because Vitamin D can be made by the body, it’s technically not a vitamin, since a vitamin by definition is something that can’t be made by the body. There are 5 forms of vitamin D found in nature, but the body only makes one, Vitamin D3, also called cholecalciferol. Even when vitamin D has been synthesised from cholesterol, it is still not active, and there are two more steps needed until it becomes active.

The first step is the conversion to calcidiol, which happens in the liver. Calcidiol is then converted to calcitriol which is the active form of vitamin D. This step happens primarily in the kidney and is controlled by parathyroid hormone, calcium and phosophate concentrations in the blood, and the concentration of calcitriol in the blood.

Now that our vitamin D is finally active it circulates in the blood and acts like a hormone. When it reaches the cell, it binds to the vitamin D receptor also called the calcitriol receptor. This whole thing then forms a big complex with the retinoid X receptor, or RXR receptor. Finally the RXR receptor needs to be bound by Vitamin A, making a big structure composed of calcitriol, the vitamin D receptor, the RXR receptor and vitamin A. This complex won’t be active until Vitamin A is present, which effectively means that Vitamin D is useless unless Vitamin A is also available in the cell. When activated, this complex binds specific areas of DNA and increases transcription of some dna and decreases transcription of other dna.

functions of vitamin D
Probably the most famous role of vitamin D is to increase the level of calcium in the blood.
it does this by
Promoting absorption of calcium from the gastrointestinal tract, meaning that we get more calcium from the food that we eat
Reducing the amount of calcium that is lost in the urine, by Increasing reabsorption in the kidneys
stimulating calcium release from bone by activating osteoclast cells

Vitamin D also has effects on the parathyroid gland. It acts to stop parathyroid cells from proliferating too much. when the parathyroid gland becomes vitamin D deficient, it starts to grow to a bigger size than it is meant to and secretes too much parathyroid hormone, resulting in hyperparathyroidism. Vitamin D stops parathyroid cells from proliferating too much

Vitamin D also has a role in the immune system with vitamin D deficiency and excess both having negative effects. Macrophages, dendritic cells, B cells and T cells can respond to and synthesise calcitriol. Earlier I said that the conversion of calcidiol to calcitriol happens primarily in the kidney but another place that this can happen is in immune cells.

Vitamin D can also lead to the production of antibacterial peptides such as cathelicidin and beta defensin 4. These work by disrupting the cell membranes of bacteria, causing them to die.

Summary
So, in summary, the skin produces vitamin D from cholesterol when exposed to UVB sunlight.
Vitamin D is converted to Calcitriol and is then active
The most well known role of calcitriol is in calcium metabolism, but it has many other effects, such as in the immune system and on the parathyroid gland

Future videos are going to look the roles of vitamin D in more detail,
the amount of vitamin D that humans need and how the recommended daily allowance has been determined,
the studies that have been done on vitamin D supplementation,
what happens in deficiency and excess,
and how prevalent vitamin D deficiency is.