25-OH-Cholecalciferol

Vitamin D regulates calcium and phosphorus absorption and deposition and serum alkaline phosphatase levels. The recommended daily allowance is 5 /xg, increasing to 10 to 15 /xg in older age.109 Vitamin D3 is synthesized under UVB irradiation in the skin where it is stored and released into the circulation in a complex with the vitamin D binding protein. In liver it is hydroxylated to 25(OH)-cholecalciferol, the hormonal precursor, followed by another hydroxylation step in the... 

OH D3 is further hydroxylated at 1-position by a specific 25-OH-cholecalciferol 1-hydroxylase enz5une, primarily present in the proximal convoluted tubules of kidney, forming 1,25-dihydroxy cholecalciferol (DHCC) with the help of cytochromP-450, molecular oxygen NADPH. 1,25-dihydroxycholecalciferol, or active Vitamin D, contains three hydroxyl groups at 1, 3 and 25 positions. So it is called calcitriol and it is biologically active form of vitamin D. 

When taken orally, it follows the same route as that of other dietary lipids. It is part of the mixed micelles and ends up on the chylomicrons formed in the intestinal mucosa cells. It is then transported to the hver on the chylomicron remnants where, like the endogenously produced cholecalciferol from sunlight, it is hydroxylated to 25- OH-cholecalciferol. 

The initial 25-hydroxylation occurs in the liver to form 25-OH-cholecalciferol or 25-OH-ergocalciferol (collectively termed 25-OHD). 25-OHD has a circulating tj of 19 days, andnormal levels are 30-80 ng/mL. Because of its prolonged tj and precursor role in the production of calcitriol, measurement of serum 25-OHD is the preferred test to evaluate sufficiency of body stores of vitamin D. 

Ergosterol is the provitamin of vitamin D2, which differs from 7-dehy-drocholesterol and vitamin D3, respectively, only by having a double bond between C22 and C23 and a methyl group at C24. Vitamin D2 is the constituent in many commercial vitamin preparations and in irradiated milk and bread. The antirachitic potencies of D2 and D3 in humans are equal, but both must be converted to 25-(OH)-cholecalciferol and eventually to the active form calcitriol (1,25-(0H)2D3) for biologic activity. 

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. 

In the human body, cholecalciferol and ergocalciferol undergo two metabolic transformations to yield the active vitamin D molecule. These are additions of hydroxyl groups, first in the liver to produce 25-hydroxyvitamin D and then in the kidney. The final product has the unwieldy name la, 25-dihydroxycholecalciferol, and is more commonly known by its simpler name 1,25-dihydroxy vitamin D or, even more simply, l,25(OH)2D. 

OH) 2 cholecalciferol Sterol Intestine Bone Facilitation of calcium and phosphorus absorption increase in bone resorption in conjunction with PTH... 

IL-10 knockout mice IBD vitamin D deficiency accelerates inflammation, progression is blocked and symptoms ameliorate when treated with l,25(OH)2-cholecalciferol [138]... 

Gannage-Yared observed that administration of cholecalciferol (vitamin D3) in combination with calcium to healthy postmenopausal women did not change serum IL-6 or TNF-a although the levels of the bioactive metabolite l,25(OH)2D3 were significantly increased [161]. 

Vitamin D is unique in that it can be either obtained from the diet (as vitamin D2 or D3) or synthesized from a cholesterol precursor, a process that requires reactions in the skin, liver, and intestine. The calciferols, including several forms of vitamin D, are a family of steroids that affect calcium homeostasis (Fig. 34.26). Cholecalciferol (vitamin D3) requires ultraviolet light for its production from 7-dehydrocholesterol present in cutaneous tissues (skin) in animals and from ergosterol in plants. This irradiation cleaves the carbon-carbon bond at C9-C10 to open the B ring to form cholecalciferol, an inactive precursor of l,25-(OH)2-cholecalciferol (calcitriol). Calcitriol is the most potent biologically active form of vitamin D (see Fig. 34.26). 

Derived from cholesterol, vitamin D is biosynthesized from its prohormone cholecalciferol (Ds), the product of solar ultraviolet irradiation of 7-dehydrocholesterol in the skin (2). In 1966, it was first recognized that vitamin D must undergo activation via two oxidative metabolic steps (Fig. 35.2). The first oxidation to 25-hydroxycholecalciferol (25(OH)D3 calcifediol Calderol) occurs in the endoplasmic reticulum of the liver and is catalyzed by vitamin D 25-hydroxylase. This activation step is not... 

Sterol-specific cytoplasmic receptor proteins (vitamin D receptor) mediate the biological action of vitamin D (9). The active hormone is transported from the cytoplasm to the nucleus via the vitamin D receptor, and as a result of the interaction of the hormone with target genes, a variety of proteins are produced that stimulate the transport of calcium in each of the target tissues. Active vitamin D works in concert with PTH to enhance active intestinal absorption of calcium, to stimulate bone resorption, and to prohibit renal excretion of calcium (2,9). If serum calcium or 1,25-calcitriol concentrations are elevated, then vitamin D 24-hydroxylase (in renal mitochondria) is activated to oxidize 25(OH)D3 to inactive 24,25-dihydroxy-cholecalciferol and to further oxidize active vitamin D to the inactive 1,24,25-trihydroxylated derivative. Both the 1,24,25-trihydroxylated and the 24,25-dihydroxylated products have been found to suppress PTH secretion as well. Several factors have been identified in the regulation of the biosynthesis of vitamin D, including low phosphate concentrations (stimulatory) as well as pregnancy and lactation (stimulatory). 

In this line it is shown one of the first studies which aimed to ascertain at what intestinal level the Sr/Ca discrirnination takes place. Vitamin D3, 25-hydroxy-cholecaldferol (25-OH-CC) and 1,25-dihydroxy-cholecalciferol (1,25 (OH)2-CC) were administered to rats. The apparent and... 

Cholecalciferol, traditionally and erroneously named vitamin D, represents a secosteroidal hormone inhumans. Biosynthesis of its activemetabolitela,25(OH)2D3 proceeds via cholesterol —> 7-dehydrocholesterol (liver) — cholecalciferol (irradiation... 

Nicotiana. Vitamin as well as 25(OH)Dj and la,25(OH)jD3were identified in the leaves of N. glauca Graham (Skliar et al. 2000). Furthermore, 7-dehydrochole-sterol known as a precursor in human cholecalciferol biosynthesis could also be detected. Furthermore, this precursor was detected in Solanum glaucophyllum sub nom. S. malacoxylon which led to the assumption that the biosynthesis of cholecalciferol and its congeners in plants might proceed on a similar pathway to that in humans (Aburjai et al. 1996). 

Utilization. Cholecalciferol—obtained either from the diet or from the irradiation of the skin—is transported by a specific vitamin D carrier protein (a globulin) to the liver where it is converted to 25-hydroxycholecalciferol (25-OH-... 

Although most of the research on vitamin D metabolism has been conducted on cholecalciferol, studies by Deluca on ergocalciferol indicate that it is metabolized similarly to cholecalciferol that it is changed to a similar active metabolite in the liver— 25-hydroxyergocalciferol (25-OH-D2). 

The terminology of the vitamin D metabolites has not changed, and relatively little new resulted from basic research on vitamin D or cholecalciferol skin biosynthesis and subsequent biotransformations in the liver and kidney (Figure 1). Understandings of the role of the hormonal form of vitamin D, 1,25-dihydroxyvitamin D (l,25(OH)2D3), in intestinal absorbing cells have been expanded. In addition, new information suggests that the consumption of dietary calcium at adequate levels may reduce the critical need for vitamin D for the maintenance of serum calcium concentration. New information is also emerging on the role of vitamin D in patients with chronic renal failure and in the prevention of colon cancer. 

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