Vitamin d metabolism
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Vitamin D Metabolism: An Overview
Introduction to Vitamin D Metabolism
Vitamin D is a crucial steroid hormone involved in calcium metabolism and bone homeostasis. It is synthesized in the skin upon exposure to ultraviolet (UV) radiation, converting 7-dehydrocholesterol to vitamin D3 (cholecalciferol) 24. Additionally, vitamin D can be ingested through dietary sources such as fish oils, fortified foods, and to a lesser extent, dairy products 24.
Key Steps in Vitamin D Metabolism
Liver Hydroxylation
The first critical step in vitamin D metabolism occurs in the liver, where vitamin D3 is hydroxylated to form 25-hydroxyvitamin D3 (25(OH)D3), the major circulating form of the vitamin 245. This metabolite is only slightly more active than the parent vitamin D.
Kidney Hydroxylation
The second hydroxylation step takes place in the kidney, converting 25(OH)D3 to the highly active form, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) 245. This active form is essential for stimulating intestinal calcium absorption and bone calcium mobilization 35.
Regulation of Vitamin D Metabolism
Feedback Mechanisms
The synthesis of 1,25(OH)2D3 is tightly regulated by feedback mechanisms involving serum calcium, phosphorus, and parathyroid hormone levels 235. Low dietary and serum calcium and phosphorus levels increase the conversion of 25(OH)D3 to 1,25(OH)2D3, while high levels decrease it 24. Parathyroid hormone enhances this conversion, adapting vitamin D metabolism to calcium deficiency 24.
Role of Enzymes
Enzymes such as CYP2R1 in the liver and 1α-hydroxylase in the kidney play pivotal roles in these hydroxylation processes 16. Mutations in these enzymes can lead to clinical manifestations such as rickets and other metabolic bone diseases 6.
Vitamin D Receptor and Genomic Effects
The vitamin D receptor (VDR) mediates the cellular actions of 1,25(OH)2D3. VDR binding sites are located in various genomic regions, and the recruitment of co-regulatory complexes by liganded VDR leads to changes in gene expression 16. This regulation is crucial for the diverse physiological actions of vitamin D, including its roles in the immune system and cardiovascular health 1.
Extraskeletal Effects of Vitamin D
Beyond its well-known role in bone health, vitamin D has several extraskeletal effects. It plays a significant role in the immune system, cardiovascular system, and regulation of cellular differentiation and proliferation 19. Vitamin D also has anti-cancer properties and is involved in the regulation of insulin resistance, obesity, and metabolic syndrome 10.
Clinical Implications
Understanding the metabolism of vitamin D has significant clinical implications. For instance, patients with chronic renal disease, vitamin D-dependency disease, and hypoparathyroidism often have failures in the 1-hydroxylating mechanism, leading to deficiencies in active vitamin D 3. Advances in the study of vitamin D metabolites and their analogs are paving the way for new treatments for vitamin D-resistant bone diseases 37.
Conclusion
Vitamin D metabolism is a complex process involving multiple hydroxylation steps in the liver and kidney, regulated by various feedback mechanisms. The active form, 1,25(OH)2D3, plays a crucial role in calcium and phosphorus metabolism, with significant implications for bone health and various extraskeletal functions. Understanding these processes is essential for developing new therapeutic strategies for metabolic bone diseases and other conditions related to vitamin D deficiency.
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Most relevant research papers on this topic
An Update on Vitamin D Metabolism
Vitamin D metabolism has evolved to include skin role, liver control, and extraskeletal effects, including benefits for the immune and cardiovascular systems.
Highly CitedVITAMIN D METABOLISM
Vitamin D metabolism involves two hydroxylation reactions, with calcium and phosphorus levels affecting the conversion of 25-hydroxy vitamin D3 to 1,25 dihydroxy vitamin D3.
Metabolism and mechanism of action of vitamin D.
Vitamin D functions as a prohormone, regulating calcium and phosphorus metabolism, with implications for understanding and treating metabolic bone disease.
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Vitamin D production and metabolism in the skin promotes skeletal health, wound healing, and hair growth, while limiting cancer development.
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Advances in LC/MS/MS technology have enabled the detection of new vitamin D metabolites in human serum, potentially impacting our understanding of vitamin D metabolism and its role in human health.
Highly CitedMetabolism of vitamin D: current status.
Vitamin D3 metabolism involves rapid accumulation in the liver, kidneys, and intestine, with 1,25-(OH)2D3 playing a crucial role in calcium and phosphate mobilization and possibly other functions.
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Vitamin D metabolism plays a crucial role in maintaining calcium homeostasis, regulating cellular differentiation, proliferation, immunity, and reproduction, with implications for clinical laboratory testing and preventing hip fractures in the elderly.
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