negative regulation of vitamin D biosynthetic process

Definition

Target type: biologicalprocess

Any process that decreases the rate, frequency or extent of a vitamin D biosynthetic process. Vitamin D biosynthesis is the chemical reactions and pathways resulting in the formation of vitamin D, any of a group of related, fat-soluble compounds that are derived from delta-5,7 steroids and play a central role in calcium metabolism. Specific forms of vitamin D include calciferol (ergocalciferol; vitamin D2) and cholecalciferol (calciol; vitamin D3). [GOC:BHF, GOC:dph, GOC:tb]

Negative regulation of vitamin D biosynthesis is a complex process that involves a series of steps aimed at reducing the production of vitamin D, also known as calciferol. Vitamin D is synthesized in the skin upon exposure to ultraviolet B (UVB) radiation, where 7-dehydrocholesterol is converted into cholecalciferol (vitamin D3). This precursor then undergoes two hydroxylation steps in the liver and kidneys, ultimately forming the active hormone 1,25-dihydroxyvitamin D3 (calcitriol).

Negative regulation of this biosynthetic pathway is essential for maintaining optimal levels of circulating calcitriol, as excessive levels can lead to hypercalcemia and other adverse effects. This regulatory mechanism involves a variety of factors, including feedback inhibition by calcitriol itself, modulation by parathyroid hormone (PTH), and the influence of other hormones and nutrients.

1. **Calcitriol Feedback Inhibition:** Calcitriol, the active form of vitamin D, acts as a negative regulator of its own synthesis by directly suppressing the expression of key enzymes involved in the process. These enzymes include 1α-hydroxylase, which converts 25-hydroxyvitamin D3 to calcitriol in the kidneys, and CYP27A1, responsible for the initial hydroxylation step in the liver. This negative feedback loop ensures that calcitriol production is tightly controlled and does not exceed the body's requirements.

2. **Parathyroid Hormone Regulation:** Parathyroid hormone (PTH) plays a crucial role in calcium homeostasis and indirectly influences vitamin D biosynthesis. When blood calcium levels are low, PTH is released, stimulating 1α-hydroxylase activity in the kidneys, leading to increased calcitriol production. Conversely, when calcium levels are high, PTH secretion is suppressed, reducing 1α-hydroxylase activity and thus lowering calcitriol synthesis.

3. **Other Hormonal and Nutritional Influences:** Several other hormones and nutrients can modulate vitamin D biosynthesis, including:

* **Growth hormone:** Stimulates vitamin D production.
* **Insulin-like growth factor-1:** Increases 1α-hydroxylase activity.
* **Estrogen:** Suppresses 1α-hydroxylase activity.
* **Calcium:** High calcium levels directly inhibit 1α-hydroxylase activity.
* **Phosphorus:** Low phosphorus levels stimulate 1α-hydroxylase activity.

4. **Cellular Mechanisms:** The regulation of vitamin D biosynthesis involves various cellular mechanisms, including:

* **Transcriptional regulation:** Calcitriol, PTH, and other factors bind to specific receptors that alter the expression of genes involved in vitamin D metabolism.
* **Post-translational modifications:** Enzymes involved in vitamin D biosynthesis are subject to phosphorylation, ubiquitination, and other modifications that can influence their activity.
* **Cellular trafficking:** Vitamin D synthesis and degradation can be affected by the trafficking of enzymes within the cell, such as the movement of 1α-hydroxylase from the cytoplasm to the mitochondria.

In summary, negative regulation of vitamin D biosynthesis is a multifaceted process involving feedback loops, hormonal influences, and cellular mechanisms that work together to maintain optimal levels of circulating calcitriol, ensuring proper calcium homeostasis and overall health.'
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Proteins (1)

Compounds (56)