#calcidiol

[alimentacaoedireitos]

[themicronut]

Functions of vitamin D (WageningenX: NUTR102x Nutrition and Health Part 2: Micronutrients and Malnutrition)

The classic role of vitamin D is to regulate calcium and phosphorus metabolism. By governing calcium metabolism, vitamin D contributes to the proper functioning of muscles and nerves, and plays a key role in bone formation and mineralization.

GENOMIC FUNCTION OF VITAMIN D

Calcitriol functions like a steroid hormone. To perform its biological roles, calcitriol binds to a specific receptor called the vitamin D receptor (VDR), which is located in the nuclei of target cells. The binding of calcitriol to VDR is followed by binding of VDR to the vitamin A-activated RXR receptor. The VDR-RXR complex binds to DNA and thereby turns on a large number of genes in a wide variety of tissues. These tissues include bone, kidney, and intestine—tissues involved in the maintenance of calcium homeostasis—as well as immune, endocrine, hematopoietic, skin, and tumor cells. For example, in the intestine calcitriol induces the production of several proteins including a calcium channel (TRPV6), calcium-binding proteins (calbindins), calcium pumps, an ATPase, and alkaline phosphatase, which are all involved in calcium absorption in the intestine.

More information about the role of vitamin D in calcium metabolism is provided in section 4.2.

EXTRA: ROLES OF VITAMIN D IN NON-CALCIFIED TISSUES

The fact that calcitriol and vitamin D receptors are present in tissues that aren’t directly involved in calcium metabolism suggests that vitamin D has other functions not related to calcium. In many cases, however, responses to calcitriol are observed at concentrations two to three orders of magnitude greater than circulating levels. It is thus possible that certain cells are dependent on local production of calcitriol. In this respect, it should be mentioned that recent research suggests that calcitriol can be made by activated macrophages, an important type of white blood cell. It has also been reported that calcitriol affects the proliferation, differentiation and immune function of white blood cells. Vitamin D receptors have also been identified in a variety of tumor cells. Experiments in the lab showed that at low concentrations, calcitriol stimulates growth, while at higher concentrations it inhibits proliferation and stimulates programmed cell death. Whether vitamin D really could affect immune status or cancer risk in humans is still being debated.

EXTRA: NON-GENOMIC FUNCTION OF VITAMIN D

In addition to regulating DNA, calcitriol is known to have so called non-genomic actions. In intestinal cells, calcitriol recruits membrane calcium transport proteins located in small cavities close to the cell surface, resulting in a rapid increase in calcium absorption before the (genomic) induction of calbindins. In some cells, calcitriol acts via cell-surface receptors and not via the nuclear VDR, which results in the extremely rapid opening of intracellular calcium channels and subsequent activation of an intracellular signaling cascade. This effect is thought to inhibit cell proliferation and promote cell differentiation.