What are the primary names and abbreviations used for calcifediol?

Calcifediol is also known by several other names and abbreviations, including calcidiol, 25-hydroxycholecalciferol, and 25-hydroxyvitamin D3. Its abbreviation is commonly 25(OH)D3.

Where and how is calcifediol initially produced in the body?

Calcifediol is produced in the liver. It is formed through the hydroxylation of vitamin D3 (cholecalciferol) by an enzyme called vitamin D 25-hydroxylase.

What is the role of calcifediol in the activation pathway of vitamin D?

Calcifediol serves as a precursor to the active hormonal form of vitamin D, calcitriol. It undergoes a further hydroxylation step, primarily in the kidneys, catalyzed by the enzyme 25(OH)D-1α-hydroxylase, to become calcitriol (1,25-(OH)2D3).

How is calcifediol transported in the blood?

In the bloodstream, calcifediol is strongly bound by a protein known as the vitamin D-binding protein, which is also referred to as gc-globulin.

Why is measuring serum calcifediol levels important in medical practice?

Measuring serum calcifediol is the standard clinical test used to determine an individual's vitamin D status. It helps diagnose vitamin D deficiency or confirm vitamin D sufficiency.

Is calcifediol available as a medication?

Yes, calcifediol is available as an oral medication in certain countries. It is used to supplement vitamin D status.

What is the chemical formula and molar mass of calcifediol?

The chemical formula for calcifediol is C27H44O2, and its molar mass is 400.64 grams per mole.

What is the ATC code assigned to calcifediol?

Calcifediol is classified under the Anatomical Therapeutic Chemical (ATC) classification system with the code H05BX05.

What is the legal status of calcifediol in Canada?

In Canada, calcifediol is classified as a prescription-only medication.

Which enzyme is primarily responsible for the 25-hydroxylation of vitamin D3 in the liver?

The enzyme primarily responsible for converting vitamin D3 (cholecalciferol) to calcifediol (25-hydroxycholecalciferol) in the liver is CYP2R1, which is located in the microsomes. However, the mitochondrial enzyme CYP27A1 can also contribute to this process.

How does obesity affect circulating calcifediol levels?

Variations in the expression and activity of the CYP2R1 enzyme, such as lower levels observed in individuals with obesity, can affect the circulating levels of calcifediol.

Besides vitamin D3, what other form of vitamin D can be 25-hydroxylated, and what is its product?

Vitamin D2, also known as ergocalciferol, can also undergo 25-hydroxylation. This process forms 25-hydroxyergocalciferol, which is also referred to as ercalcidiol or 25(OH)D2.

How are the metabolites of vitamin D2 and D3 measured in blood tests?

Clinical blood tests for vitamin D status typically measure the total level of 25-hydroxyvitamin D, often referred to as 25(OH)D. This measurement usually combines both calcifediol (25(OH)D3) and ercalcidiol (25(OH)D2) without differentiating between them.

What is the typical time frame for calcifediol levels to peak after taking a large dose of vitamin D3?

When a large dose of vitamin D3 (100,000 IU) is administered, it takes approximately 7 days for the resulting calcifediol concentrations to reach their peak levels in the body.

What is the elimination half-life of calcifediol in the body?

Calcifediol has an elimination half-life of approximately 15 to 30 days.

Which enzyme is responsible for converting calcifediol to calcitriol, and where does this primarily occur?

The conversion of calcifediol to calcitriol (the active form of vitamin D) is carried out by the enzyme 25(OH)D-1α-hydroxylase, predominantly in the kidneys.

What regulates the activity of the 25(OH)D-1α-hydroxylase enzyme (CYP27B1) in the kidneys?

The activity of the CYP27B1 enzyme, which performs the 1-alpha-hydroxylation of calcifediol, is primarily regulated by parathyroid hormone. It is also influenced by FGF23 and calcitriol itself.

In which extra-renal tissues can CYP27B1 be found, suggesting local calcitriol synthesis?

The CYP27B1 enzyme is also expressed in various other tissues beyond the kidneys, including macrophages, monocytes, keratinocytes, the placenta, and the parathyroid gland. This extra-renal expression indicates that calcitriol can be synthesized locally in these tissues from calcifediol.

What is the process of 24-hydroxylation involving calcifediol, and which enzyme performs it?

Calcifediol can also be converted into 24,25-dihydroxycholecalciferol through a process called 24-hydroxylation. This enzymatic reaction is carried out by the enzyme CYP24A1, which is present in many vitamin D target tissues and is induced by calcitriol.

What is the significance of the 24-hydroxylation pathway for calcitriol?

The 24-hydroxylation pathway, mediated by CYP24A1, leads to the inactivation of calcitriol, converting it into calcitroic acid. However, the intermediate product, 24,25-(OH)2D3, may possess some biological activities of its own.

What is the primary purpose of the 25(OH)D blood test in clinical settings?

The 25(OH)D blood test is used to assess an individual's vitamin D status, helping to diagnose conditions like vitamin D deficiency. It is particularly important for individuals at high risk and can guide the initiation of vitamin D replacement therapy.

What units are typically used to report 25(OH)D levels in the US and other countries?

In the United States, 25(OH)D levels are generally reported in nanograms per milliliter (ng/mL). Other countries commonly use nanomoles per liter (nmol/L), and the conversion factor is that 1 ng/mL is equivalent to 2.5 nmol/L.

Which patient groups are considered at higher risk for vitamin D deficiency and might be more likely to undergo a 25(OH)D test?

Patients with conditions such as osteoporosis, chronic kidney disease, malabsorption issues, and obesity are often at a greater risk for vitamin D deficiency. Consequently, they are more likely to be tested for their 25(OH)D levels.

Are vitamin D screening tests routinely recommended for the general population?

No, the 25(OH)D test is not typically recommended for the entire general population, even though vitamin D deficiency is common in certain groups, such as those with limited sun exposure. Physicians might suggest over-the-counter vitamin D supplements for low-risk individuals instead of screening.

What are the generally recommended ranges for 25(OH)D levels for vitamin D sufficiency?

According to MedlinePlus, the recommended range for 25(OH)D is typically 20 to 40 ng/mL (50 to 100 nmol/L), although many experts suggest a range of 30 to 50 ng/mL (75 to 125 nmol/L) for sufficiency. Some studies define levels below 80 nmol/L (32 ng/mL) as indicative of deficiency.

How do increasing calcifediol levels relate to calcium absorption from the gut?

Increasing calcifediol levels, up to approximately 80 nmol/L (32 ng/mL), are associated with an enhanced absorption of calcium from the digestive tract.

What potential advantages does calcifediol have over cholecalciferol for correcting vitamin D deficiency?

Calcifediol may offer advantages over cholecalciferol in treating vitamin D deficiency states. Studies suggest calcifediol is more potent, better absorbed from the intestine, has a higher affinity for vitamin-D-binding protein (increasing bioavailability), and is eliminated more quickly.

In which patient populations might the pharmacokinetic properties of calcifediol be particularly beneficial?

The properties of calcifediol, such as better absorption and faster elimination, may be particularly beneficial for individuals experiencing intestinal malabsorption, those who are obese, or patients taking certain medications that can affect vitamin D metabolism.

What specific FDA-approved use does calcifediol have in the treatment of chronic kidney disease?

In 2016, the FDA approved a formulation of calcifediol (Rayaldee) for daily use as a prescription medication. It is indicated for treating secondary hyperparathyroidism in patients who have chronic kidney disease.

According to the provided pathway map, what is the precursor to calcifediol?

According to the Vitamin D Synthesis pathway map, cholecalciferol is the direct precursor to calcifediol.

Which enzyme is shown in the pathway map as converting cholecalciferol to calcifediol?

The Vitamin D Synthesis pathway map indicates that CYP2R1 is the enzyme responsible for converting cholecalciferol to calcifediol.

What are the two main products of calcifediol metabolism shown in the pathway map?

The pathway map shows that calcifediol can be converted into calcitriol (1,25-dihydroxycholecalciferol) and 24,25-dihydroxycholecalciferol.

Who were the key researchers involved in the initial identification and isolation of calcifediol and its synthesizing enzyme?

The identification of 25(OH)D (calcifediol) and the necessity of the liver for its formation were established in the laboratory of Hector DeLuca in 1968. The enzyme responsible for this synthesis, cholecalciferol 25-hydroxylase, was later isolated by Michael F. Holick in the same laboratory in 1972.

What is the current status of research involving calcifediol compared to other forms of vitamin D?

Research is ongoing to compare the effects of calcifediol with other vitamin D forms, such as cholecalciferol, particularly in the prevention and treatment of osteoporosis.

How does calcifediol metabolism differ in teleost fish compared to humans?

In teleost fish, calcifediol is predominantly converted to calcitriol within the liver, rather than in the kidneys as seen in humans. This difference means that circulating calcifediol levels in these fish can be undetectable, requiring alternative methods to assess vitamin D status.

What has been the outcome of using dietary calcifediol supplementation in salmonids?

Dietary supplementation with calcifediol has shown success in salmonid fish, leading to improvements in growth rates and food conversion ratios.

What is the chemical structure of calcifediol represented by?

The chemical structure of calcifediol is represented by a skeletal formula and a ball-and-stick model in the provided source material.

What is the Preferred IUPAC name for calcifediol?

The Preferred IUPAC name for calcifediol is (1S,3Z)-3-[(2E)-2-{(1R,3aS,7aR)-1-[(2R)-6-Hydroxy-6-methylheptan-2-yl]-7a-methyloctahydro-4H-inden-4-ylidene}ethylidene]-4-methylidenecyclohexan-1-ol.

What are the identifiers listed for calcifediol in the provided information?

Calcifediol is identified by its CAS Number (19356-17-3), ChEBI ID (CHEBI:17933), ChEMBL ID (ChEMBL1222), ChemSpider ID (4446820), DrugBank ID (DB00146), ECHA InfoCard (100.039.067), IUPHAR/BPS ID (6921), KEGG ID (C01561), MeSH identifier, PubChem CID (5283731), UNII (T0WXW8F54E), and CompTox Dashboard ID (DTXSID0022721). It also has InChI and SMILES representations.

What is the significance of the 'verify' link and the 'X' mark next to some data in the infobox?

The 'verify' link and the 'X' mark (indicating 'N' for No) next to certain data points in the infobox suggest that the information might require verification or is not confirmed. Conversely, a checkmark ('Y' for Yes) indicates confirmed data.

What does the statement 'Except where otherwise noted, data are given for materials in their standard state' imply about the provided properties?

This statement indicates that the physical and chemical properties listed in the infobox, such as molar mass, are presented under standard conditions, typically defined as 25 degrees Celsius (77 degrees Fahrenheit) and 100 kilopascals of pressure. This ensures consistency in data reporting.

What is the relationship between calcifediol and vitamin D-binding protein?

Calcifediol binds strongly in the blood to a protein called vitamin D-binding protein (also known as gc-globulin). This binding is significant for its transport and availability in the body.

What is the primary function of calcifediol in the context of vitamin D status assessment?

Calcifediol is the main circulating metabolite of vitamin D. Its concentration in the blood is the most reliable indicator of a person's overall vitamin D status, reflecting both dietary intake and the body's production and storage of vitamin D.

What is the role of CYP24A1 in vitamin D metabolism?

CYP24A1 is an enzyme that performs 24-hydroxylation on vitamin D metabolites, including calcifediol. This process is part of the pathway to inactivate vitamin D and its metabolites, eventually leading to calcitroic acid.

What is the significance of the 'Interactive pathway map' section?

The 'Interactive pathway map' section provides a visual representation of the Vitamin D Synthesis pathway. It allows users to click on various components like genes, proteins, and metabolites to link to their respective articles, offering a dynamic way to explore the biological processes involved.

What does the presence of multiple navboxes (Vitamins, Calcium homeostasis, Vitamin D receptor modulators) at the end of the article suggest about calcifediol?

The inclusion of multiple navboxes indicates that calcifediol is interconnected with broader biological and medical categories. It is classified under vitamins, plays a role in calcium homeostasis, and functions as a vitamin D receptor modulator, highlighting its multifaceted biological significance.

What is the relationship between calcifediol and the 'standard state' mentioned in the infobox?

The 'standard state' refers to defined conditions (typically 25°C and 100 kPa) under which physical and chemical properties of a substance, like calcifediol, are measured and reported for consistency. This ensures that comparisons of properties are made under uniform conditions.

How does calcifediol's bioavailability compare to cholecalciferol, and why?

Calcifediol exhibits greater bioavailability than cholecalciferol. This is attributed to its better absorption from the intestine and a higher affinity for the vitamin-D-binding protein in the blood, which facilitates its transport and distribution.

Calcifediol Wiki: Calcifediol Unveiled: The Vitamin D Metabolite

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Introduction

Definition and Nomenclature

Calcifediol, also known by synonyms such as calcidiol, 25-hydroxycholecalciferol, or 25-hydroxyvitamin D₃ (abbreviated 25(OH)D₃), is a crucial metabolite of vitamin D. It is synthesized in the liver through the hydroxylation of vitamin D₃ (cholecalciferol) by the enzyme vitamin D 25-hydroxylase (primarily CYP2R1, with contributions from CYP27A1).^[1]^[3]^[4]^[5]

Precursor to Active Vitamin D

Calcifediol serves as the direct precursor to calcitriol (1,25-(OH)₂D₃), the biologically active hormonal form of vitamin D. This conversion occurs primarily in the kidneys via the enzyme 25(OH)D-1α-hydroxylase (CYP27B1), a process tightly regulated by factors such as parathyroid hormone (PTH), FGF23, and calcitriol itself.^[3]^[4]^[5] Notably, extra-renal synthesis of calcitriol from calcifediol also occurs in other tissues, including macrophages and monocytes.^[8]

Circulating Marker of Vitamin D Status

Calcifediol is transported in the blood, predominantly bound to the vitamin D-binding protein (VDBP).^[5] The measurement of serum calcifediol levels is the standard clinical method for assessing an individual's vitamin D status, enabling the diagnosis of deficiency or confirmation of sufficiency.^[4]^[5]

Biological Significance

Hepatic Synthesis and Regulation

The transformation of vitamin D₃ into calcifediol occurs in the liver via 25-hydroxylation, primarily catalyzed by CYP2R1 within the hepatic microsomes. While CYP27A1 also contributes, variations in CYP2R1 expression, potentially influenced by conditions like obesity, can affect circulating calcifediol concentrations.^[5]^[8] Vitamin D₂ (ergocalciferol) undergoes a similar process to form 25-hydroxyergocalciferol (ercalcidiol), and clinical assays typically measure the combined total 25(OH)D.^[1]^[3]

Pharmacokinetics

Following oral administration, calcifediol reaches peak serum concentrations within approximately 7 days, even with large doses. Its elimination half-life is estimated to be between 15 to 30 days.^[4]^[9] Calcifediol binds strongly to vitamin D-binding protein (VDBP), influencing its distribution and bioavailability.^[5]

Metabolic Pathways

Calcifediol is further metabolized through two primary pathways: 1α-hydroxylation to the active calcitriol by CYP27B1, and 24-hydroxylation to the inactive 24,25-dihydroxycholecalciferol by CYP24A1. The latter pathway serves to inactivate calcitriol and is induced by calcitriol itself.^[3]^[5]

Diagnostic Utility

Assessing Vitamin D Status

The measurement of 25-hydroxyvitamin D (25(OH)D), encompassing both calcifediol and ercalcidiol, is the gold standard for evaluating vitamin D sufficiency. Levels are typically reported in nanograms per milliliter (ng/mL) or nanomoles per liter (nmol/L), with a conversion factor of 2.5 (ng/mL × 2.5 = nmol/L).^[4] While ranges vary, levels between 20-40 ng/mL (50-100 nmol/L) are generally considered sufficient, though some experts advocate for higher targets.^[11]

Clinical Indications and Standardization

Testing is often indicated for individuals at risk of deficiency, including those with osteoporosis, chronic kidney disease, malabsorption syndromes, obesity, or certain medical conditions.^[15] Despite its clinical importance, there is a recognized need for improved standardization and reproducibility across different laboratory assays.^[4]^[13]

Impact on Calcium Absorption

Serum calcifediol levels correlate positively with intestinal calcium absorption. Optimal absorption is generally observed up to approximately 80 nmol/L (32 ng/mL), with urinary calcium excretion remaining balanced until much higher levels are reached.^[13]^[18]

Supplementation and Therapy

Advantages Over Cholecalciferol

Calcifediol supplements may offer advantages over standard vitamin D₃ (cholecalciferol) for correcting deficiency states. Studies indicate calcifediol is approximately 3.2 times more potent, likely due to its enhanced intestinal absorption and greater affinity for VDBP, leading to improved bioavailability.^[6]^[20] Its faster elimination profile may also be beneficial in specific patient populations, such as those with intestinal malabsorption or obesity.^[20]

Therapeutic Applications

Calcifediol is indicated for various conditions, including vitamin D deficiency, refractory rickets, familial hypophosphatemia, hypoparathyroidism, hypocalcemia, and renal osteodystrophy. It is also used, in conjunction with calcium, for managing primary or corticosteroid-induced osteoporosis.^[19] In 2016, the FDA approved a formulation (Rayaldee) for treating secondary hyperparathyroidism in patients with chronic kidney disease.^[7]

Historical Context

Key Discoveries

The significance of calcifediol was elucidated through pivotal research. Its identification in human plasma and the demonstration of the liver's role in its formation were reported by Ponchon, Kennan, and DeLuca in 1969.^[21] Subsequently, Michael F. Holick and colleagues isolated the responsible enzyme, cholecalciferol 25-hydroxylase, in 1972.^[22]

Vitamin D Synthesis Pathway

Key Intermediates and Enzymes

The metabolic journey of vitamin D involves several key molecular transformations. Starting from cholesterol, it progresses through 7-dehydrocholesterol, which is converted to previtamin D₃ and then to cholecalciferol (vitamin D₃) via thermal isomerization. The liver then hydroxylates cholecalciferol to calcifediol (25(OH)D₃) using enzymes like CYP2R1 and CYP27A1. Calcifediol is subsequently hydroxylated in the kidneys by CYP27B1 to form the active calcitriol (1,25-(OH)₂D₃), or inactivated by CYP24A1 to 24,25-dihydroxycholecalciferol. The vitamin D-binding protein plays a crucial role in transporting these metabolites throughout the body. Other related molecules include ergocalciferol (vitamin D₂) and its metabolites, as well as receptors like the Vitamin D Receptor (VDR) and Retinoid X Receptors (RXRs).

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References

"25-hydroxy vitamin D test: Medline Plus". Retrieved 4 March 2021.

A full list of references for this article are available at the Calcifediol Wikipedia page

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Important Notice

This content has been generated by an Artificial Intelligence model and is intended for educational and informational purposes only. While efforts have been made to ensure accuracy based on the provided source material, it may not be exhaustive or entirely up-to-date. The information presented here is derived from publicly available data and should not be considered a substitute for professional medical advice, diagnosis, or treatment.

This is not medical advice. Always consult with a qualified healthcare provider or physician for any health concerns or before making any decisions related to your health or treatment. Never disregard professional medical advice or delay seeking it because of information obtained from this resource. The creators assume no responsibility for any errors or omissions or for any actions taken based on the information provided.

Calcifediol Unveiled

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Introduction ℹ️

🧬 Definition and Nomenclature

🔬 Precursor to Active Vitamin D

🩸 Circulating Marker of Vitamin D Status

Biological Significance 🔬

⚙️ Hepatic Synthesis and Regulation

⏳ Pharmacokinetics

🔄 Metabolic Pathways

Diagnostic Utility 🩸

📈 Assessing Vitamin D Status

❓ Clinical Indications and Standardization

⚖️ Impact on Calcium Absorption

Supplementation and Therapy 💊

⬆️ Advantages Over Cholecalciferol

🏥 Therapeutic Applications

Historical Context 📜

💡 Key Discoveries

Vitamin D Synthesis Pathway ➡️

🔗 Key Intermediates and Enzymes

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📜 Important Notice

Dive in with Flashcard Learning!

Introduction

Definition and Nomenclature

Precursor to Active Vitamin D

Circulating Marker of Vitamin D Status

Biological Significance

Hepatic Synthesis and Regulation

Pharmacokinetics

Metabolic Pathways

Diagnostic Utility

Assessing Vitamin D Status

Clinical Indications and Standardization

Impact on Calcium Absorption

Supplementation and Therapy

Advantages Over Cholecalciferol

Therapeutic Applications

Historical Context

Key Discoveries

Vitamin D Synthesis Pathway

Key Intermediates and Enzymes

Teacher's Corner

True or False?

Test Your Knowledge!

Gamer's Corner

Discover other topics to study!

References

Feedback & Support

Disclaimer

Important Notice