DB00146 - Calcidiol
| Identification | |
|---|---|
| Name | Calcidiol |
| Accession Number | DB00146 (APRD00428, NUTR00006) |
| Type | small molecule |
| Description | The major circulating metabolite of vitamin D3 (cholecalciferol). It is produced in the liver and is the best indicator of the body's vitamin D stores. It is effective in the treatment of rickets and osteomalacia, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties. [PubChem] |
| Structure |
|
| Categories (*) | |
| Molecular Weight | 400.6371 |
| Groups | approved |
| Monoisotopic Weight | 400.334130652 |
| Pharmacology | |
| Indication | Used to treat vitamin D deficiency or insufficiency, refractory rickets (vitamin D resistant rickets), familial hypophosphatemia and hypoparathyroidism, and in the management of hypocalcemia and renal osteodystrophy in patients with chronic renal failure undergoing dialysis. Also used in conjunction with calcium in the management and prevention of primary or corticosteroid-induced osteoporosis. |
| Mechanism of action | Calcidiol is transformed in the kidney by 25-hydroxyvitamin D3-1-(alpha)-hydroxylase to calcitriol, the active form of vitamin D3. Calcitriol binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription. Calcitriol increases the serum calcium concentrations by: increasing GI absorption of phosphorus and calcium, increasing osteoclastic resorption, and increasing distal renal tubular reabsorption of calcium. Calcitriol appears to promote intestinal absorption of calcium through binding to the vitamin D receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein. |
| Absorption | Readily absorbed. |
| Protein binding | Not Available |
| Biotransformation | Calcidiol undergoes hydroxylation in the mitochondria of kidney tissue, and this reaction is activated by the renal 25-hydroxyvitamin D3-1-(alpha)-hydroxylase to produce calcitriol (1,25- dihydroxycholecalciferol), the active form of vitamin D3. |
| Route of elimination | Not Available |
| Toxicity | Bone pain, constipation (especially in children or adolescents), diarrhea, drowsiness, dryness of mouth; headache (continuing), increased thirst, increase in frequency of urination, especially at night, or in amount of urine, irregular heartbeat, itching skin, loss of appetite, metallic taste, muscle pain, nausea or vomiting (especially in children or adolescents), unusual tiredness or weakness. |
| Affected organisms |
|
| Interactions | |
| Drug Interactions | Not Available |
| Food Interactions | Not Available |
Targets
| Vitamin D3 receptor | |
|---|---|
| Name | Vitamin D3 receptor |
| Gene Name | VDR |
| Pharmacological action | yes |
| Actions | agonist |
| References | |
| DTHybrid score | 1.4917 |
Enzymes
| 25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial | |
|---|---|
| Name | 25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial |
| Gene Name | CYP27B1 |
| Actions | substrate |
| References |
|
| DTHybrid score | 0.8173 |
| Cytochrome P450 24A1, mitochondrial | |
| Name | Cytochrome P450 24A1, mitochondrial |
| Gene Name | CYP24A1 |
| Actions | substrate |
| References |
|
| DTHybrid score | 0.946 |
Predictions
| Id | Partner name | Gene Name | Score |
|---|---|---|---|
| 1992 | Vitamin D-binding protein | GC | 0.1905 |
| 945 | Adrenocorticotropic hormone receptor | MC2R | 0.1686 |
| 581 | Cytochrome P450 2R1 | CYP2R1 | 0.1682 |
| 606 | Cytochrome P450 27, mitochondrial | CYP27A1 | 0.1453 |
| 1566 | Corticoliberin | CRH | 0.1257 |
| 66 | 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type II | HSD3B2 | 0.1162 |
| 4512 | Cytochrome P450 3A4 | CYP3A4 | 0.1106 |
| 6891 | Mediator of RNA polymerase II transcription subunit 1 | MED1 | 0.0935 |
| 6228 | Nuclear receptor coactivator 1 | NCOA1 | 0.0897 |
| 1757 | Myeloperoxidase | MPO | 0.0768 |
| 6025 | UDP-glucuronosyltransferase 1-4 | UGT1A4 | 0.0666 |
| 6182 | Cytochrome P450 2J2 | CYP2J2 | 0.0079 |
| 6017 | Cholesterol side-chain cleavage enzyme, mitochondrial | CYP11A1 | 0.006 |
| 6024 | Cytochrome P450 1A1 | CYP1A1 | 0.0041 |
| 6030 | Cytochrome P450 2B6 | CYP2B6 | 0.0039 |
| 4924 | Cytochrome P450 2C8 | CYP2C8 | 0.0036 |
| 6016 | Cytochrome P450 2C19 | CYP2C19 | 0.0034 |
| 4757 | Cytochrome P450 2C9 | CYP2C9 | 0.0033 |
| 4119 | Cytochrome P450 2D6 | CYP2D6 | 0.0032 |