colecalciferol

Cholecalciferol
	IUPAC name (3β,5Z,7E)-9,10-secocholesta-; 5,7,10(19)-trien-3-ol
	Other names vitamin D3, activated 7-dehydrocholesterol.
Identifiers
CAS number	67-97-0 =
ChemSpider	9058792
UNII	1C6V77QF41
EC number	200-673-2
DrugBank	DB00169
ChEMBL	CHEMBL1042
ATC code	A11CC05
Jmol-3D images	Image 1
	SMILES O[C@@H]1CC(\C(=C)CC1)=C\C=C2/CCC[C@]3(C2CC[C@@H]3[C@H](C)CCCC(C)C)C ;
	InChI InChI=1S/C27H44O/c1-19(2)8-6-9-21(4)25-15-16-26-22(10-7-17-27(25,26)5)12-13-23-18-24(28)14-11-20(23)3/h12-13,19,21,24-26,28H,3,6-11,14-18H2,1-2,4-5H3/b22-12+,23-13-/t21-,24+,25-,26?,27-/m1/s1 ; Key: QYSXJUFSXHHAJI-QWSSABAFSA-N InChI=1/C27H44O/c1-19(2)8-6-9-21(4)25-15-16-26-22(10-7-17-27(25,26)5)12-13-23-18-24(28)14-11-20(23)3/h12-13,19,21,24-26,28H,3,6-11,14-18H2,1-2,4-5H3/b22-12+,23-13-/t21-,24+,25-,26?,27-/m1/s1; Key: QYSXJUFSXHHAJI-QWSSABAFBD ;
Properties
Molecular formula	C27H44O
Molar mass	384.64 g/mol
Appearance	White, needle-like crystals
Melting point	83–86 °C
	(verify) (what is: /?); Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
	Infobox references

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関: cholecalciferol

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/04/26 21:46:10」(JST)

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Cholecalciferol is a form of vitamin D, also called vitamin D₃ or calcitriol.^[1]^[2]

It is structurally similar to steroids such as testosterone, cholesterol, and cortisol (though vitamin D₃ itself is a secosteroid).

Forms

Vitamin D₃ has several forms:

Cholecalciferol, (sometimes called calciol) is an inactive, unhydroxylated form of vitamin D₃)
Calcifediol (also called calcidiol, hydroxycholecalciferol, 25-hydroxyvitamin D₃, etc. and abbreviated 25(OH)D is one of the forms measured in the blood to assess vitamin D status^[3]
Calcitriol (also called 1,25-dihydroxyvitamin D₃) is the active form of D₃.

Metabolism

7-Dehydrocholesterol is the precursor of vitamin D₃. Within the epidermal layer of skin^[4], 7-Dehydrocholesterol undergoes a retro-Diels–Alder reaction as a result of UVB radiation, resulting in the opening of the vitamin precursor B-ring through a conrotatory pathway. Following this, the previtamin D₃ undergoes a [1,7] antarafacial sigmatropic rearrangement ^[5] and therein finally isomerizes to form vitamin D₃.

Cholecalciferol is then hydroxylated in the liver to become calcifediol (25-hydroxyvitamin D₃).

Next, calcifediol is again hydroxylated, this time in the kidney, and becomes calcitriol (1,25-dihydroxyvitamin D₃). Calcitriol is the most active hormone form of vitamin D₃.

Regulation of metabolism

Cholecalciferol is synthesized in the skin from 7-dehydrocholesterol under the action of ultraviolet B light. It reaches an equilibrium after several minutes depending on several factors including conditions of sunlight (latitude, season, cloud cover, altitude), age of skin, and color of skin.
Hydroxylation in the endoplasmic reticulum of liver hepatocytes of cholecalciferol to calcifediol (25-hydroxycholecalciferol) by 25-hydroxylase is loosely regulated, if at all, and blood levels of this molecule largely reflect the amount of vitamin D₃ produced in the skin or the vitamin D₂ or D₃ ingested.
Hydroxylation in the kidneys of calcifediol to calcitriol by 1-alpha-hydroxylase is tightly regulated (stimulated by either parathyroid hormone or hypophosphatemia) and serves as the major control point in production of the most active circulating hormone calcitriol (1,25-dihydroxyvitamin D₃).

Industrial production

Cholecalciferol is produced industrially for use in vitamin supplements and to fortify foods by the ultraviolet irradiation of 7-dehydrocholesterol extracted from lanolin found in sheep's wool. Paraphrasing a more detailed explanation ^[6], cholesterol is extracted from wool grease and wool wax alcohols obtained from the cleaning of wool after shearing. The cholesterol undergoes a four step process to make 7-dehydrocholesterol, the same compound that is stored in the skin of animals. The 7-dehydrocholesterol is then irradiated with ultra violet light. Some unwanted isomers are formed during irradiation. These are removed by various techniques, leaving a resin which melts at about room temperature and usually has a potency of 25,000,000 to 30,000,000 International Units per gram.

In foods where animal products are not desired, an alternative compound is ergocalciferol (also known as vitamin D₂) derived from the fungal sterol ergosterol.

Dose

One gram is 40,000,000 (40x10⁶) IU, equivalently 1 IU is 0.025 µg.

Recommendations are: 15 µg/d (600 IU per day) for all individuals (males, female, pregnant/lactating women) under the age of 70 years-old. For all individuals older than 70 years, 20 µg/d (800 IU per day) is recommended.^[7] A growing body of researchers question whether the current recommended adequate levels are sufficient to meet physiological needs, particularly for individuals deprived of regular sun exposure or those at higher risk such as those with higher-melanin content in the skin (i.e. those whose ancestors are African, Middle Eastern, Latin American, or Asian), the obese, and those who live far from the equator. The upper limit (UL) for vitamin D has been recommended as 4,000 IU daily. The 4,000 IU cut-off was determined by the Institute of Medicine in 2010 after reviewing the then-current medical literature, finding that toxicity had consistently occurred when doses of 40,000 IU daily were taken,^[8] and that there was a single case of toxicity above 10,000 IU daily; this case of toxicity occurred under circumstances which have led other researchers to dispute it as a credible case to consider when making vitamin D intake recommendations.^[8] The Institute of Medicine did not find evidence of toxicity between 4,000 IU and 10,000 IU, so the 4,000 IU number is more of an estimate than a number based on evidence of toxicity above 4,000 IU.^[7] Patients with severe vitamin D deficiency will require treatment with a loading dose, its magnitude can be calculated based on the actual serum 25-hydroxy-vitamin D level and body weight.^[9] However, there also exists a hypothesis which disadvises from supplementing vitamin D if not really necessary: Vitamin D might support the emergence of allergies and adulterate already existing allergies and autoimmune diseases.^[10] But that is merely an unproved hypothesis.

Also, there is a therapy for rickets utilizing a single dose, called stoss therapy in Europe - taking from 300,000 IU (7,500 µg) to 500,000 IU (12,500 µg = 12.5 mg), as a single dose, or two to four divided doses.^[11]

The 25-hydroxy vitamin D (calcifediol) blood test is used to determine how much vitamin D is in the body. The normal range of calcifediol is 30.0 to 74.0 ng/mL.^[3]

"Vitamin D toxicity can result from regular excess intake of this vitamin, and may lead to hypercalcemia and excess bone loss. Individuals at particular risk include those with hyperparathyroidism, kidney disease, sarcoidosis, tuberculosis, or histoplasmosis. Chronic hypercalcemia may lead to serious or even life-threatening complications, and should be managed by a physician. Early symptoms of hypercalcemia may include nausea, vomiting, and anorexia (appetite/weight loss), followed by polyuria (excess urination), polydipsia (excess thirst), weakness, fatigue, somnolence, headache, dry mouth, metallic taste, vertigo, tinnitus (ear ringing), and ataxia (unsteadiness). Kidney function may become impaired, and metastatic calcifications (calcium deposition in organs throughout the body) may occur, particularly affecting the kidneys. Treatment involves stopping the intake of vitamin D or calcium, and lowering the calcium levels under strict medical supervision, with frequent monitoring of calcium levels. Acidification of urine and corticosteroids may be necessary."^[12]

There are conflicting reports concerning the absorption of cholecalciferol (D₃) versus ergocalciferol (D₂), with some studies suggesting less efficacy of D₂,^[13] and others showing no difference.^[14] At present, D₂ and D₃ doses are frequently considered interchangeable, but more research is needed to clarify this.

Stability

Cholecalciferol is very sensitive to UV radiation and will rapidly, but reversibly, break down to form sura-sterols, which can further irreversibly convert to ergosterol.

Preventative application

A 2008 study published in Cancer Research has shown the addition of vitamin D₃ (along with calcium) to the diet of some mice fed a regimen similar in nutritional content to a new Western diet with 1000 IU cholecaliferol per day prevented colon cancer development.^[15] In humans, with 400 IU daily, there was no effect.^[16]

Toxicity

Rodents are somewhat more susceptible to high doses than other species, and cholecalciferol has been used in poison bait for the control of these pests. It has been claimed that the compound is less toxic to non-target species. However, in practice it has been found that use of cholecalciferol in rodenticides represents a significant hazard to other animals, such as dogs and cats. "Cholecalciferol produces hypercalcemia, which results in systemic calcification of soft tissue, leading to renal failure, cardiac abnormalities, hypertension, CNS depression, and GI upset. Signs generally develop within 18-36 hr of ingestion and can include depression, anorexia, polyuria, and polydipsia."^[17]

In New Zealand, possums have become a significant pest animal, and cholecalciferol has been used as the active ingredient in lethal gel baits and cereal pellet baits "DECAL" for possum control. The LD₅₀ is 16.8 mg/kg, but only 9.8 mg/kg if calcium carbonate is added to the bait.^[18]^[19]

Kidneys and heart are target organs.^[20]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^[21]

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Vitamin D Synthesis Pathway edit

References

^ "Nomenclature of Vitamin D. Recommendations 1981. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN)" reproduced at the Queen Mary, University of London website. Retrieved 21 March 2010.
^ "cholecalciferol" at Dorland's Medical Dictionary
^ ^a ^b ""25-hydroxy vitamin D test: Medline Plus". Retrieved 21 March 2010.
^ Norman, Anthony W. (1998) Sunlight, season, skin pigmentation, vitamin D, and 25-hydroxyvitamin D:integral components of the vitamin D endocrine system. Am J Clin Nutr;67:1108–10.
^ Okamura, W. H., Elnagar, H. Y., Ruther, M. & S. Dobreff. (1993). "Thermal [1,7]-sigmatropic shift of previtamin D₃ to vitamin D₃: synthesis and study of pentadeuterio derivatives". Journal of Organic Chemistry 58: 600–610. doi:10.1021/jo00055a011.
^ http://www.agdnutrition.com/d3-story.html Vitamin D3 Story.] Retrieved 8 April 2012.
^ ^a ^b DRIs for Calcium and Vitamin D
^ ^a ^b Vieth R (May 1999). "Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety". Am. J. Clin. Nutr. 69 (5): 842–56. PMID 10232622.
^ van Groningen L, Opdenoordt S, van Sorge A, Telting D, Giesen A, de Boer H (April 2010). "Cholecalciferol loading dose guideline for vitamin D-deficient adults". Eur. J. Endocrinol. 162 (4): 805–11. doi:10.1530/EJE-09-0932. PMID 20139241.
^ MP Study Results [1]
^ Shah BR, Finberg L (September 1994). "Single-day therapy for nutritional vitamin D-deficiency rickets: a preferred method". J. Pediatr. 125 (3): 487–90. doi:10.1016/S0022-3476(05)83303-7. PMID 8071764.
^ Vitamin D: MedlinePlus Supplements with the National Academy of Sciences dosing recommendations at the Medline Plus website.
^ Armas LA, Hollis BW, Heaney RP (November 2004). "Vitamin D2 is much less effective than vitamin D3 in humans". J. Clin. Endocrinol. Metab. 89 (11): 5387–91. doi:10.1210/jc.2004-0360. PMID 15531486.
^ Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, Bibuld D, Reitz R, Salameh W, Ameri A, Tannenbaum AD (March 2008). "Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D". J. Clin. Endocrinol. Metab. 93 (3): 677–81. doi:10.1210/jc.2007-2308. . PMID 18089691. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2266966.
^ Yang K, Kurihara N, Fan K, Newmark H, Rigas B, Bancroft L, Corner G, Livote E, Lesser M, Edelmann W, Velcich A, Lipkin M, Augenlicht L (October 2008). "Dietary induction of colonic tumors in a mouse model of sporadic colon cancer". Cancer Res. 68 (19): 7803–10. doi:10.1158/0008-5472.CAN-08-1209. PMID 18829535.
^ Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O'Sullivan MJ, Margolis KL, Ockene JK, Phillips L, Pottern L, Prentice RL, Robbins J, Rohan TE, Sarto GE, Sharma S, Stefanick ML, Van Horn L, Wallace RB, Whitlock E, Bassford T, Beresford SA, Black HR, Bonds DE, Brzyski RG, Caan B, Chlebowski RT, Cochrane B, Garland C, Gass M, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Jackson RD, Johnson KC, Judd H, Kooperberg CL, Kuller LH, LaCroix AZ, Lane DS, Langer RD, Lasser NL, Lewis CE, Limacher MC, Manson JE (February 2006). "Calcium plus vitamin D supplementation and the risk of colorectal cancer". N. Engl. J. Med. 354 (7): 684–96. doi:10.1056/NEJMoa055222. PMID 16481636.
^ "Merck Veterinary Manual - Rodenticide Poisoning: Introduction". http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/213000.htm.
^ Morgan D (2006). "Field efficacy of cholecalciferol gel baits for possum (Trichosurus vulpecula) control". New Zealand Journal of Zoology 33 (3): 221–8. doi:10.1080/03014223.2006.9518449.
^ Jolly SE, Henderson RJ, Frampton C, Eason CT (1995). "Cholecalciferol Toxicity and Its Enhancement by Calcium Carbonate in the Common Brushtail Possum". Wildlife Research 22 (5): 579–83. doi:10.1071/WR9950579.
^ "Kiwicare Material Safety Data Sheet". http://www.kiwicare.co.nz/index.cfm/3,80,144/no-possums-cholecalciferol-gel-bait.pdf.
^ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531". http://www.wikipathways.org/index.php/Pathway:WP1531.

External links

NIST Chemistry WebBook page for cholecalciferol
University of California TV - What’s a Vitamin D Deficiency?
University of California TV - Dose-Response of Vitamin D and a Mechanism for Cancer Prevention

English Journal

Vitamin D(3) improves respiratory adjustment to fatigue and H-reflex responses in paraplegic adult rats.

Bianco J, Gueye Y, Marqueste T, Alluin O, Risso JJ, Garcia S, Lavault MN, Khrestchatisky M, Feron F, Decherchi P.SourceInstitut des Sciences du Mouvement : Etienne-Jules MAREY (ISM : EJM), UMR CNRS 6233, Universite de la Mediterranee (Aix-Marseille II - Aix-Marseille Universite), Parc Scientifique et Technologique de Luminy - Faculte des Sciences du Sport de Marseille - CC910 - 163, avenue de Luminy - 13288 Marseille cedex 09 - France; Neurobiologie des Interactions Cellulaires et Neurophysiopathologie (NICN), CNRS UMR 6184, Universite de la Mediterranee (Aix-Marseille II - Aix-Marseille Universite), Faculte de Medecine Nord, Institut Federatif de Recherche Jean Roche (IFR11) - 51 boulevard Pierre Dramard - 13916 Marseille cedex 20 - France.
Neuroscience.Neuroscience.2011 Aug 11;188C:182-192. Epub 2011 May 7.
We previously demonstrated that vitamin D(2) (ergocalciferol) triggers axon regeneration in a rat model of peripheral nerve transection. In order to confirm the regenerative potential of this neuroactive steroid, we performed a study in which vitamin D(3) (cholecalciferol) was delivered at various d
PMID 21571043

Optimal vitamin D, calcitriol, and vitamin D analog replacement in chronic kidney disease: to D or not to D: that is the question.

Moorthi RN, Kandula P, Moe SM.SourceaDivision of Nephrology, Indiana University School of Medicine, USA bRoudebush Veterans Administration Medical Center, Indianapolis, Indiana, USA.
Current opinion in nephrology and hypertension.Curr Opin Nephrol Hypertens.2011 Jul;20(4):354-9.
PMID 21654391

Related Pictures

[0] "Nomenclature of Vitamin D. Recommendations 1981. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN)" reproduced at the Queen Mary, University of London website. Retrieved 21 March 2010.

[1] "cholecalciferol" at Dorland's Medical Dictionary

[BloodTest-2] ""25-hydroxy vitamin D test: Medline Plus". Retrieved 21 March 2010.

[Norman-3] Norman, Anthony W. (1998) Sunlight, season, skin pigmentation, vitamin D, and 25-hydroxyvitamin D:integral components of the vitamin D endocrine system. Am J Clin Nutr;67:1108–10.

[4] Okamura, W. H., Elnagar, H. Y., Ruther, M. & S. Dobreff. (1993). "Thermal [1,7]-sigmatropic shift of previtamin D₃ to vitamin D₃: synthesis and study of pentadeuterio derivatives". Journal of Organic Chemistry 58: 600–610. doi:10.1021/jo00055a011.

[AGD_Nutrition-5] ttp://www.agdnutrition.com/d3-story.html Vitamin D3 Story.] Retrieved 8 April 2012.

[Institute_of_Medicine-6] DRIs for Calcium and Vitamin D

[pmid10232622-7] Vieth R (May 1999). "Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety". Am. J. Clin. Nutr. 69 (5): 842–56. PMID 10232622.

[pmid20139241-8] van Groningen L, Opdenoordt S, van Sorge A, Telting D, Giesen A, de Boer H (April 2010). "Cholecalciferol loading dose guideline for vitamin D-deficient adults". Eur. J. Endocrinol. 162 (4): 805–11. doi:10.1530/EJE-09-0932. PMID 20139241.

[9] MP Study Results [1]

[pmid8071764-10] Shah BR, Finberg L (September 1994). "Single-day therapy for nutritional vitamin D-deficiency rickets: a preferred method". J. Pediatr. 125 (3): 487–90. doi:10.1016/S0022-3476(05)83303-7. PMID 8071764.

[MedlinePlusSupplements-11] Vitamin D: MedlinePlus Supplements with the National Academy of Sciences dosing recommendations at the Medline Plus website.

[pmid15531486-12] Armas LA, Hollis BW, Heaney RP (November 2004). "Vitamin D2 is much less effective than vitamin D3 in humans". J. Clin. Endocrinol. Metab. 89 (11): 5387–91. doi:10.1210/jc.2004-0360. PMID 15531486.

[pmid18089691-13] Holick MF, Biancuzzo RM, Chen TC, Klein EK, Young A, Bibuld D, Reitz R, Salameh W, Ameri A, Tannenbaum AD (March 2008). "Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D". J. Clin. Endocrinol. Metab. 93 (3): 677–81. doi:10.1210/jc.2007-2308. . PMID 18089691. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2266966.

[pmid18829535-14] Yang K, Kurihara N, Fan K, Newmark H, Rigas B, Bancroft L, Corner G, Livote E, Lesser M, Edelmann W, Velcich A, Lipkin M, Augenlicht L (October 2008). "Dietary induction of colonic tumors in a mouse model of sporadic colon cancer". Cancer Res. 68 (19): 7803–10. doi:10.1158/0008-5472.CAN-08-1209. PMID 18829535.

[pmid16481636-15] Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O'Sullivan MJ, Margolis KL, Ockene JK, Phillips L, Pottern L, Prentice RL, Robbins J, Rohan TE, Sarto GE, Sharma S, Stefanick ML, Van Horn L, Wallace RB, Whitlock E, Bassford T, Beresford SA, Black HR, Bonds DE, Brzyski RG, Caan B, Chlebowski RT, Cochrane B, Garland C, Gass M, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Jackson RD, Johnson KC, Judd H, Kooperberg CL, Kuller LH, LaCroix AZ, Lane DS, Langer RD, Lasser NL, Lewis CE, Limacher MC, Manson JE (February 2006). "Calcium plus vitamin D supplementation and the risk of colorectal cancer". N. Engl. J. Med. 354 (7): 684–96. doi:10.1056/NEJMoa055222. PMID 16481636.

[16] "Merck Veterinary Manual - Rodenticide Poisoning: Introduction". http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/213000.htm.

[17] Morgan D (2006). "Field efficacy of cholecalciferol gel baits for possum (Trichosurus vulpecula) control". New Zealand Journal of Zoology 33 (3): 221–8. doi:10.1080/03014223.2006.9518449.

[18] Jolly SE, Henderson RJ, Frampton C, Eason CT (1995). "Cholecalciferol Toxicity and Its Enhancement by Calcium Carbonate in the Common Brushtail Possum". Wildlife Research 22 (5): 579–83. doi:10.1071/WR9950579.

[19] "Kiwicare Material Safety Data Sheet". http://www.kiwicare.co.nz/index.cfm/3,80,144/no-possums-cholecalciferol-gel-bait.pdf.

[WikiPathways-20] The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531". http://www.wikipathways.org/index.php/Pathway:WP1531.

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