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Calcifediol
Calcifediol, also known as calcidiol, 25-hydroxycholecalciferol, or 25-hydroxyvitamin D3 (abbreviated 25(OH)D3), is a form of vitamin D produced in the liver by hydroxylation of vitamin D3 (cholecalciferol) by the enzyme vitamin D 25-hydroxylase. Calcifediol can be further hydroxylated by the enzyme 25(OH)D-1α-hydroxylase, primarily in the kidney, to form calcitriol (1,25-(OH)2D3), which is the active hormonal form of vitamin D. Calcifediol is strongly bound in blood by the vitamin D-binding protein. Measurement of serum calcifediol is the usual test performed to determine a person's vitamin D status, to show vitamin D deficiency or sufficiency. Calcifediol is available as an oral medication in some countries to supplement vitamin D status. Biology Calcifediol is the precursor for calcitriol, the active form of vitamin D. It is synthesized in the liver, by hydroxylation of cholecalciferol (vitamin D3) at the 25-position. This enzymatic 25-hydroxylase reaction is mostly due t ...
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Vitamin D
Vitamin D is a group of structurally related, fat-soluble compounds responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions. In humans, the most important compounds within this group are vitamin D3 ( cholecalciferol) and vitamin D2 ( ergocalciferol). Unlike the other twelve vitamins, vitamin D is only conditionally essential, as with adequate skin exposure to the ultraviolet B (UVB) radiation component of sunlight there is synthesis of cholecalciferol in the lower layers of the skin's epidermis. For most people, skin synthesis contributes more than diet sources. Vitamin D can also be obtained through diet, food fortification and dietary supplements. In the U.S., cow's milk and plant-based milk substitutes are fortified with vitamin D3, as are many breakfast cereals. Government dietary recommendations typically assume that all of a person's vitamin D is taken by mouth, given the potential for ...
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Vitamin D3
Cholecalciferol, also known as vitamin D3, colecalciferol or calciol, is a type of vitamin D that is produced by the skin when exposed to UVB light; it is found in certain foods and can be taken as a dietary supplement. Cholecalciferol is synthesised in the skin following sunlight exposure. It is then converted in the liver to calcifediol (25-hydroxycholecalciferol D), which is further converted in the kidney to calcitriol (1,25-dihydroxycholecalciferol D). One of calcitriol's most important functions is to promote calcium uptake by the intestines. Cholecalciferol is present in food such as fatty fish, beef liver, eggs, and cheese. In some countries, cholecalciferol is also added to products like plants, cow milk, fruit juice, yogurt, and margarine. Cholecalciferol can be taken orally as a dietary supplement to prevent vitamin D deficiency or as a medication to treat associated diseases, including rickets. It is also used in the management of familial hypophosphatemi ...
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Vitamin D Deficiency
Vitamin D deficiency or hypovitaminosis D is a vitamin D level that is below normal. It most commonly occurs in people when they have inadequate exposure to sunlight, particularly sunlight with adequate ultraviolet B rays (UVB). Vitamin D deficiency can also be caused by inadequate nutritional intake of vitamin D; disorders that limit vitamin D absorption; and disorders that impair the conversion of vitamin D to active metabolites, including certain liver, kidney, and hereditary disorders. Deficiency impairs bone mineralization, leading to bone-softening diseases, such as rickets in children. It can also worsen osteomalacia and osteoporosis in adults, increasing the risk of bone fractures. Muscle weakness is also a common symptom of vitamin D deficiency, further increasing the risk of falls and bone fractures in adults. Vitamin D deficiency is associated with the development of schizophrenia. Vitamin D can be synthesized in the skin under exposure to UVB from sunlight. Oily ...
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Calcitriol
Calcitriol is a hormone and the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the expression of many genes. Calcitriol increases blood Calcium in biology, calcium mainly by increasing the uptake of calcium from the intestines. It can be given as a medication for the treatment of hypocalcemia, low blood calcium and hyperparathyroidism due to kidney disease, low blood calcium due to hypoparathyroidism, osteoporosis, osteomalacia, and familial hypophosphatemia, and can be taken by mouth or by intravenous, injection into a vein. Excessive amounts or intake can result in weakness, headache, nausea, constipation, urinary tract infections, and abdominal pain. Serious side effects may include high blood calcium and anaphylaxis. Calcitriol was identified as the active form of vitamin D in 1971 and the drug was approved for medic ...
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CYP2R1
CYP2R1 is cytochrome P450 2R1, an enzyme which is the principal vitamin D 25-hydroxylase. In humans it is encoded by the ''CYP2R1'' gene located on chromosome 11p15.2. It is expressed in the endoplasmic reticulum in liver, where it performs the first step in the activation of vitamin D by catalyzing the formation of 25-hydroxyvitamin D. Vitamin D 25-hydroxylase activity is also possessed by some other cytochrome P450 enzymes, in particular CYP27A1, which is found in mitochondria. Function CYP2R1 is a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are mono-oxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. CYP2R1 is present in the endoplasmic reticulum of the liver (the microsomal fraction). It has 25-hydroxylase activity, which converts cholecalciferol (vitamin D3) into calcifediol (25-hydroxyvitamin D3, also known as calcidiol), the major circulatory form of the v ...
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CYP27B1
25-Hydroxyvitamin D 1-alpha-hydroxylase (VD 1A hydroxylase) also known as calcidiol 1-monooxygenase or cytochrome p450 27B1 (CYP27B1) or simply 1-alpha-hydroxylase is a cytochrome P450 enzyme that in humans is encoded by the ''CYP27B1'' gene. VD 1A hydroxylase is located in the proximal tubule of the kidney and a variety of other tissues, including skin (keratinocytes), immune cells, and bone (osteoblasts). Reactions The enzyme catalyzes the hydroxylation of calcifediol to calcitriol (the bioactive form of Vitamin D): :calcidiol + 2 reduced adrenodoxin + 2 H+ + O2 calcitriol + 2 oxidized adrenodoxin + H2O The enzyme is also able to oxidize ercalcidiol (25-OH D2) to ercalcitriol, secalciferol to calcitetrol, and 25-hydroxy-24-oxocalciol to (1S)-1,25-dihydroxy-24-oxocalciol. Image:Calcidiol2.svg, Calcidiol Image:Calcitriol.svg , Calcitriol Calcitriol is a hormone and the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydrox ...
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Vitamin D-binding Protein
Vitamin D-binding protein (DBP), also/originally known as gc-globulin (group-specific component), is a protein that in humans is encoded by the ''GC'' gene. DBP is genetically the oldest member of the albuminoid family and appeared early in the evolution of vertebrates. Structure Human GC is a glycosylated alpha-globulin, ~58 kDa in size. Its 458 amino acids are coded for by 1690 nucleotides on chromosome 4 (4q11–q13). The primary structure contains 28 cysteine residues forming multiple disulfide bonds. GC contains 3 domains. Domain 1 is composed of 10 alpha helices, domain 2 of 9, and domain 3 of 4. Function Vitamin D-binding protein belongs to the albumin gene family, together with human serum albumin and alpha-fetoprotein. It is a multifunctional protein found in plasma, ascitic fluid, cerebrospinal fluid and on the surface of many cell types. It is able to bind the various forms of vitamin D including ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3), the 25- ...
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25-Hydroxyvitamin D3 1-alpha-hydroxylase
25-Hydroxyvitamin D 1-alpha-hydroxylase (VD 1A hydroxylase) also known as calcidiol 1-monooxygenase or cytochrome p450 27B1 (CYP27B1) or simply 1-alpha-hydroxylase is a cytochrome P450 enzyme that in humans is encoded by the ''CYP27B1'' gene. VD 1A hydroxylase is located in the proximal tubule of the kidney and a variety of other tissues, including skin (keratinocytes), immune cells, and bone (osteoblasts). Reactions The enzyme catalyzes the hydroxylation of calcifediol to calcitriol (the bioactive form of Vitamin D): :calcidiol + 2 reduced adrenodoxin + 2 H+ + O2 calcitriol + 2 oxidized adrenodoxin + H2O The enzyme is also able to oxidize ercalcidiol (25-OH D2) to ercalcitriol, secalciferol to calcitetrol, and 25-hydroxy-24-oxocalciol to (1S)-1,25-dihydroxy-24-oxocalciol. Image:Calcidiol2.svg, Calcidiol Image:Calcitriol.svg , Calcitriol Calcitriol is a hormone and the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxyc ...
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CYP24A1
Cytochrome P450 family 24 subfamily A member 1 (abbreviated CYP24A1) is a member of the cytochrome P450 superfamily of enzymes encoded by the ''CYP24A1'' gene. It is a mitochondrial monooxygenase which catalyzes reactions including 24-hydroxylation of calcitriol (1,25-dihydroxyvitamin D3). It has also been identified as vitamin D3 24-hydroxylase.() Function CYP24A1 is an enzyme expressed in the mitochondrion of humans and other species. It catalyzes hydroxylation reactions which lead to the degradation of 1,25-dihydroxyvitamin D3, the physiologically active form of vitamin D. Hydroxylation of the side chain produces calcitroic acid and other metabolites which are excreted in bile. CYP24A1 was identified in the early 1970s and was first thought to be involved in vitamin D metabolism as the renal 25-hydroxyvitamin D3-24-hydroxylase, modifying calcifediol (25-hydroxyvitamin D) to produce 24,25-dihydroxycholecalciferol (24,25-dihydroxyvitamin D). Subsequent studies using rec ...
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FGF23
Fibroblast growth factor 23 (FGF-23) is a protein and member of the fibroblast growth factor (FGF) family which participates in the regulation of phosphate in plasma and vitamin D metabolism. In humans it is encoded by the gene. FGF-23 decreases reabsorption of phosphate in the kidney. Mutations in ''FGF23'' can lead to its increased activity, resulting in autosomal dominant hypophosphatemic rickets. Description Fibroblast growth factor 23 (FGF23) is a protein which in humans is encoded by the gene. FGF23 is a member of the fibroblast growth factor (FGF) family which participates in phosphate and vitamin D metabolism and regulation. Function FGF23´s main function is to regulate the phosphate concentration in plasma. It does this by decreasing reabsorption of phosphate in the kidney, which means phosphate is excreted in urine. FGF23 is secreted by osteocytes in response to increased calcitriol and phosphate. FGF23 acts on the kidneys by decreasing the expression of NPT2, a ...
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