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 Y=  Y
ChemSpider	9058792 Y
UNII	1C6V77QF41 Y
EC number	200-673-2
DrugBank	DB00169
ChEMBL	CHEMBL1042 N
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 Y Key: QYSXJUFSXHHAJI-QWSSABAFSA-N Y 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
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

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[link]

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[link]

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[link]

• 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[link]

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[link]

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 that 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 figure 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 that disadvises supplementing vitamin D if not really necessary: Vitamin D might support the emergence of allergies and adulterate already existing allergies and autoimmune diseases;^[10] however, that is merely an unproven 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), in a single dose, or in 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[link]

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[link]

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[link]

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[link]

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

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Vitamin D Synthesis Pathway edit

See also[link]

• Hypervitaminosis D, Vitamin D poisoning
• Ergocalciferol, vitamin D₂.
• 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, a kidney enzyme that converts calcifediol to calcitriol.

References[link]

External links[link]

• 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

This biographical article needs additional citations for verification. Please help by adding reliable sources. Contentious material about living persons that is unsourced or poorly sourced must be removed immediately, especially if potentially libelous or harmful. (March 2010)

Margaret Avery (born January 20, 1944) is an American actress and singer. She was nominated for an Academy Award for Best Actress in a Supporting Role for her performance as Shug in The Color Purple (1985).^[1]

Early life[link]

Born in Mangum, Oklahoma, she was raised in San Diego, California, where she attended Point Loma High School. Avery then attended San Francisco State University, earning a Bachelor of Arts degree in education. While working as a substitute teacher in Los Angeles, Avery began making singing appearances and acting on the stage.

Career[link]

Among the plays she appeared in were Revolution, and Sistuhs. For her performance in Does a Tiger Wear a Necktie? (1973) she received the Los Angeles Drama Critics Circle Award for "Performance In A Major Role."^[2]

In the television movie Something Evil (1972), a horror story with Sandy Dennis and Darren McGavin, she was directed by Steven Spielberg. That same year, she made her theatrical motion picture debut as Lark in the MGM crime/drama Cool Breeze with Thalmus Rasulala and Judy Pace. In this blaxploitation remake of The Asphalt Jungle, Avery played the Marilyn Monroe part. The following year she played a prostitute in Magnum Force (1973), the second in the series of Dirty Harry films starring Clint Eastwood, in which the character she played was murdered by her pimp (played by Albert Popwell) by having drain cleaner poured down her throat. This act of killing was said to have inspired the notorious Hi-Fi Murders case in 1974.

In Universal's Which Way Is Up? (1977), directed by Michael Schultz, Avery turned in a comedic performance as Annie Mae, the wife of Richard Pryor. That same year, she played Belle Joplin, wife of the ragtime composer Scott Joplin, opposite Billy Dee Williams in the title role.

Avery scored a major success with her role as the sultry and spirited Blues singer, Shug Avery, in Spielberg's The Color Purple (1985) opposite Whoopi Goldberg and Danny Glover. Her performance in this screen adaptation of Alice Walker's prize-winning novel of the same title earned Avery an Academy Award nomination for Best Actress in a Supporting Role.

In 1992 Avery starred in The Jacksons: An American Dream as Martha Scruse, mother of Katherine Jackson, who was played by Angela Basset. The two would later star together in Meet the Browns.

She has also made numerous TV series guest appearances, including The New Dick Van Dyke Show, Kojak, Sanford and Son, Kolchak: The Night Stalker, A.E.S. Hudson Street, Murder, She Wrote, Miami Vice, Spenser: For Hire, The Cosby Show, Walker, Texas Ranger and JAG.

In 2008, Avery played Mama Jenkins in Welcome Home Roscoe Jenkins, opposite Martin Lawrence and James Earl Jones, and Sarah Brown in Tyler Perry's Meet the Browns, which also stars Angela Bassett.

Margaret Avery lives in Los Angeles, and is active in the show business industry. While continuing to act, she also works with at-risk teenagers and battered women of Greater Los Angeles.

Personal life[link]

She married Robert Gordon Hunt in January 1974. They were divorced in 1980 and have one daughter.^{[citation needed]}

Filmography[link]

References[link]

External links[link]

• Margaret Avery Official Website
• Margaret Avery at the Internet Movie Database
• Margaret Avery at AllRovi
• Margaret Avery at TV.com