Cholecalciferol/ja: Difference between revisions

The three steps in the synthesis and activation of vitamin D₃ are regulated as follows:

* Cholecalciferol is synthesized in the skin from 7-dehydrocholesterol under the action of ultraviolet B (UVB) light. It reaches an equilibrium after several minutes depending on the intensity of the UVB in the sunlight – determined by latitude, season, cloud cover, and altitude – and the age and degree of pigmentation of the skin.

* Hydroxylation in the endoplasmic reticulum of liver [[hepatocyte]]s of cholecalciferol to calcifediol (25-hydroxycholecalciferol) by [[CYP2R1|25-hydroxylase]] is loosely regulated, if at all, and blood levels of this molecule largely reflect the amount of cholecalciferol produced in the skin combined with any vitamin D₂ or D₃ ingested.

* Hydroxylation in the kidneys of calcifediol to calcitriol by [[25-Hydroxyvitamin D3 1-alpha-hydroxylase|1-alpha-hydroxylase]] is tightly regulated: it is stimulated by [[parathyroid hormone]] and serves as the major control point in the production of the active circulating hormone [[calcitriol]] (1,25-dihydroxyvitamin D₃).

==Industrial production==

Cholecalciferol is produced industrially for use in [[multivitamin|vitamin supplement]]s and [[food fortification|to fortify foods]]. As a [[pharmaceutical drug]] it is called cholecalciferol ([[United States Adopted Name|USAN]]) or colecalciferol ([[International Nonproprietary Name|INN]], [[British Approved Name|BAN]]). It is produced by the [[ultraviolet]] irradiation of [[7-dehydrocholesterol]] extracted from [[lanolin]] found in sheep's [[wool]]. 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 produced in the skin of animals. The 7-dehydrocholesterol is then irradiated with ultraviolet 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.

Cholecalciferol is also produced industrially for use in vitamin supplements from [[lichen]]s, which is suitable for vegans.

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==Stability==

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

==Pesticide==

The mechanism of high dose cholecalciferol is that it can produce "[[hypercalcemia]], which results in systemic calcification of soft tissue, leading to [[kidney failure]], [[cardiac]] abnormalities, [[hypertension]], CNS depression, and GI upset. Signs generally develop within 18-36 hr of ingestion and can include depression, [[loss of appetite]], [[polyuria]], and [[polydipsia]]." High-dose cholecalciferol will tend to rapidly accumulate in [[adipose]] tissue yet release more slowly which will tend to delay time of death for several days from the time that high-dose bait is introduced.

In New Zealand, [[Common brushtail possum|possums]] have become a significant pest animal. For possum control, cholecalciferol has been used as the active ingredient in lethal baits. The [[Median lethal dose|LD₅₀]] is 16.8&nbsp;mg/kg, but only 9.8&nbsp;mg/kg if calcium carbonate is added to the bait. Kidneys and heart are target organs. LD₅₀ of 4.4&nbsp;mg/kg has been reported in rabbits, with lethality to almost all rabbits ingesting doses greater than 15&nbsp;mg/kg. Toxicity has been reported across a wide range of cholecalciferol dosages, with LD₅₀ as high as 88&nbsp;mg/kg or LD_Lo as low as 2&nbsp;mg/kg reported for dogs.

Researchers have reported that the compound is less toxic to non-target species than earlier generations of anticoagulant rodenticides ([[Warfarin]] and [[Congener (chemistry)|congeners]]) or [[Bromethalin]], and that [[Relay toxicity|relay toxicosis]] (poisoning by eating a poisoned animal) has not been documented. Nevertheless, the same source reports that use of cholecalciferol in [[rodenticide]]s may still pose a significant hazard to other animals, such as dogs and cats, when rodenticide bait or other forms of cholecalciferol are directly ingested.