Cholecalciferol, structure

Most vitamins function either as a hormone/ chemical messenger (cholecalciferol), structural component in some metabolic process (pantothenic acid), or a coenzyme (phytonadi-one, thiamine, riboflavin, niacin, pyridoxine, biotin, folic acid, cyanocobalamin). At least one vitamin has more than one biochemical role. Vitamin A as an aldehyde (retinal) is a structural component of the visual pigment rhodopsin and, in its acid form (retinoic acid), is a regulator of cell differentiation. The precise biochemical functions of ascorbic acid and a-tocopherol still are not well defined. 

Cholecalciferol (vitamin D-3) differs from calciferol only in the alkyl side-chain, so it was assumed to be in the twisted conformation (75a). In alcoholic solution, vitamin D-3 was irradiated with a mercury arc lamp through a cupric sulphate solution filter to give wavelengths above 250 nm. Six products were isolated. Conformation (75a) could reasonably give rise to the assigned structures (76a), (77a) and (78a) (Scheme 2.3). Photoisomerization could give conformation (75b), which would explain the isolation of (76b), (77b) and (78b). The report is confident on four of the new compounds, but notes that the cyclobutene structures (78a) and (78b) are tentatively assigned [63]. 

Vitamin D is represented by cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2), which are structurally similar secosteroids derived from the UV irradiation of provitamin D sterols. In vertebrates, vitamin D3 is produced in vivo by the action of sunlight on 7-dehydrocholesterol in the skin. Vitamin D2 is produced in plants, fungi, and yeasts by the irradiation of ergosterol. On irradiation, the provitamins are converted to previtamin D, which undergoes thermal transformation to vitamin D. 

FIGURE 29.5 Chemical structure of vitamin D (calciferol, term for a collection of fat-soluble steroid-like substances that are regulating the calcium and phosphate metabolism). Cholecalciferol (R =R2=R3=H), Calcitriol (R1=R2=OH, R3=H). 

Cholesterol is involved in two major biological processes. It is a structural component of cell membranes (Chap. 6) and the parent compound from which steroid hormones, vitamin D3 (cholecalciferol), and the bile salts are derived. Cholesterol is synthesized de novo in the liver and intestinal epithelial cells and is also derived from dietary lipid. De novo synthesis of cholesterol is regulated by the amount of cholesterol and triglyceride in the dietary lipid. 

This vitamin occurs in several forms the two most important are vitamin D2, or ergo-calciferol, and vitamin D3, or cholecalciferol. The structural formulas of these compounds are presented in Figure 9-4. Vitamin D does... 

A-9 Vitamin D is a fat-soluble vitamin (acts as a steroid hormone) and is structurally related to a group of steroids that occur mainly in animals (cholecalciferol) but also in plants and yeasts (ergosterol). 

Figure 49-17 Structure of vitamin D3 (choiecalciferol) and vitamin D2 (ergocalciferol) and their precursors. 7-Cholecalciferol is produced in the skin from 7-dehydrocho esterol on exposure to sunlight. Ergocalciferol is produced commercially by irradiation of ergosterol. (Modified from Holick MF,AdamsJS.Vitamin D metabolism and biological function. ln Avioli LV, Krone SM, eds. Metabolic bone disease, 2nd ed. Philadelphia WB Saunders, 1990 155-95.)...

The answer is b. (Murray, pp 505-626. Scriver, pp 4029-4240. Sack, pp 121—138. Wilson, pp 287-320.) Calcium ions and calcium deposits are virtually universal in the structure and function of living things. In humans, calcium ions are required lor the activity of many enzymes. Calcium is taken up Irom the gut in the presence ol lorms of vitamin D, such as cholecalciferol. Calcium is also primarily excreted through the intestine. When soluble, it is present as a divalent cation. When insoluble, it is found as hydroxyapatite (calcium phosphate) in bone. It is required by muscle cells for contraction and is sequestered into the sarcoplasmic reticulum during relaxation. It is actively transported by a calcium-ATPase across the sarcoplasmic reticulum. 

Normally, it would seem unusual to expose food to ultraviolet (UV) radiation before trying to isolate a nutrient, but starting in the 1890s reports indicated that once exposed to high levels of sunshine, humans were unlikely to develop rickets. Scientists now know that UV exposure is essential for the body to produce cholecalciferol from cholesterol. See Figure 1 for the structures of cholesterol and cholecalciferol. Cholesterol is the steroid lipid often associated with heart disease when too much is present small amounts of cholesterol are needed to make cholecalciferol and a host of other steroid hormones. Since humans can manufacture all the cholecalciferol needed for good health from exposure to sunshine, vitamin D is commonly referred to as the sunshine vitamin. 

FIGURE 7.6 Structure and function of intracellular receptors. Glucocorticoid, mineralocorticoid and androgen receptors are located in the cytoplasm. Estrogen, progesterone, thyroid hormone, 1,25-dihydroxy-cholecalciferol and retinoic acid receptors are located in the nucleus. 

Chemical structure (Figure 3). 7-Dehydrocholes-terol (provitamin D3) converted to cholecalciferol by UV irradiation enzymatic hydroxylation to 25-OH-cholecalciferol in liver enzymatic hydroxylation to la,25(OH)2 colecalciferol in kidney. 

Figure 1 Chemical structure of (A) vitamin A, all-frans-retinol (B) /i-carotene (C) vitamin D, cholecalciferol (D) vitamin E, a-tocopherol and (E) vitamin Ki(20), phylloquinone.

Figure 3 Structure of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol).

I CHOLECALCIFEROL (VITAMIN A. I Chemical structure. The sterol structure is activated by irradiation of 7-dehydrocholesterol. 

Ergocalciferol and cholecalciferol (I) have a common ring structure as represented in Fig. 1 characterized by an open ring B with three conjugated double bonds. In later sections certain pertinent structural aspects of vitamin D are discussed to present the reader with basic concepts upon which methods have been based. 

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