Hydroxy cholecalciferol

In the skin, cholesterol is converted to 7-dehydrocholes-terol by desaturation of the 9,10-carbon bond and ultraviolet light breaks this bond to produce cholecalciferol (Figure 15.12). The cholecalciferol is transported via the bloodstream to the liver where the first step in the activation of the hormone occurs, namely hydroxylation by a monooxygenase to produce 25-hydroxy cholecalciferol, which is transported to the kidney where a further hydroxylation takes place at the 1-position to produce la,25-dihydroxycholecalciferol, which is the active form of the hormone (Figure 15.13). 

The combination of rifampicin and isoniazid reduces serum concentrations of 25-hydroxy cholecalciferol. Rifampicin acts by induction of an enzyme that promotes conversion of 25-hydroxycholecalciferol to an inactive metabolite, and isoniazid acts by inhibiting 25-hydroxyla-tion and 1-hydroxylation (SEDA-14, 258). Children or pregnant women with tuberculosis have increased calcium requirements independent of rifampicin administration... 

Vitamin D is a fat soluble vitamin related to cholesterol. In the skin, sunlight spontaneously oxidizes cholesterol to 7-dehydrocholesterol. 7-Dehydrocholesterol spontaneously isomerizes to cholecalciferol (vitamin D3), which is oxidized in the liver to 25-hydroxy cholecalciferol and, under the influence of PTH in the kidney, to 1,25-dihy-droxy cholecalciferol (calcitriol), the active form of vitamin D. Vitamin D induces the expression of calcium ion transport proteins (calbindins) in intestinal epithelium, osteoclasts, and osteoblasts. Calbindins and transient receptor potential channels (TRPV) are responsible for the uptake of calcium from the diet. In children, the absence of sunlight provokes a deficiency of vitamin D, causing an absence of calbindins and inadequate blood calcium levels. Osteoid tissue cannot calcify, causing skeletal deformities (rickets). In the elderly, there is a loss of intestinal TRPV receptors and decreased calbindin expression by vitamin D. In both cases, the resultant low blood calcium levels cause poor mineralization during bone remodeling (osteomalacia). Rickets is the childhood expression of osteomalacia. Osteoclast activity is normal but the bone does not properly mineralize. In osteoporosis, the bone is properly mineralized but osteoclasts are overly active. 

Baum, J., F. Holden, M. Roginsky, M. I. Cohen, and L. Finberg 25-Hydroxy-cholecalciferol in the Management of Rickets Associated with Extra-hepatic Bilary Atresia. J. Pediatrics 88, 1041 (1976). 

Mass Fragmentographic Determination of Cholecaliferol and 25-Hydroxy-cholecalciferol in Human Serum Experientia 34(12) 1537-1539 (1978) CA 90 68739m... 

Considerable progress was made in elucidating the biotransformations of cholecalciferol (Vitamin D3) to biologically active forms. The first of these has been identified as 25-hydroxy cholecalciferol, which in turn is further metabolized to the 1,25 and perhaps also to the 21,25-dihy-droxy derivatives. Control over calcium transport is assured, since the initial hydroxylation Is obligatory in conferring biological activity and the biosynthesis of the active metabolites Is controlled by feedback regulation. Whiie these hydroxyiated derivatives, unlike Vitamin D3 itself, are all directly effective at the cellular level, there is some evidence... 

Oxidation of la-hydroxycholecalciferol and la,25-dihydroxycholecalciferol with Mn02 gave the corresponding 1 -oxo-previtamins which could be reduced with LiAlH4 at —25 °C in each case to give a mixture of la-hydroxy- and IjS-hydroxy-previtamins in which the IjS-epimers (285) and (286) predominated. Thermal equilibration allowed the isolation of the 1/3-hydroxy-cholecalciferol and l/ ,25-dihydroxycholecalciferol. A similar independent synthesis of 1/3-hydroxycholecalciferol employed NaBH4 for the reduction... 

Rubinger D, Korn-Lubetzki I, Feldman S, Popovtzer MM. Delayed response to 1 a-hydroxy-cholecalciferol therapy in a case of hypoparathyroidism during anticonvulsant therapy. IsrJ MedSci( 9S0) 16, 772-4. 

Furst, a., L. Labler, W. Meier, and K.-H. Pfoertner. Synthesis of la-Hydroxy-cholecalciferol. Helv. Chim. Acta 56, 1708 (1973). 

Infants with severe cholestasis due to 3jff-HSDH deficiency may have hypo-calcaemia due to malabsorption of vitamin D or severely deranged clotting due to malabsorption of vitamin K. Vitamins D and K should be given either parenterally or orally in a form that is absorbed despite intestinal bile salt deficiency (e.g. la-hydroxy-cholecalciferol or 1,25-dihydroxy-chole-calciferol). Fresh frozen plasma and intravenous calcium supplement may occasionally be required. 

Brandi M, Wu X, Liu Yanzhou, Pease J, Holper M, Hooijmaaijer E, Lu Yvonne, Ping W. Chemical reactivity of R0-26-9228, l-a-fluoro-25-hydroxy-16,23E-diene-26,27-bishomo-20-epi-cholecalciferol in aqueous solution. J Pharm Sci 2003 92(10). 

Quantification. High Pressure Liquid Chromatography. In plasma cholecalciferol, ergocalciferol and the 25-hydroxy metabolites, detection limit 500 pg/ml, UV detection—G. Jones, Clin. Chem., 1978,24, 287-298. 

A synthesis of 22,23-epoxyergocalciferol from the 4-phenyl-1,2,4-triazoline-3,5-dione adducts (272) employed the K2CO3-DMSO reaction for deprotection of the A -diene cf. ref. 53). The Reporter observes that the assignment of the 22/3,23/3-configuration is dubious in view of earlier work in this area. " Syntheses have been reported for la,25-dihydroxy-24-nor-cholecalciferol, 25-hydroxy-24 -nor- 5,6- frans-cholecalcif erol, and 2 5 -hydroxy- 24a-homo- 5,6-... 

The /J-adduct is formed from (5Z)-cholecalciferol by attack from above the plane of the molecule (i.e., anti to the hydroxy substituent). In fact, by assuming the endo mechanism for cycloaddition, no steric influence should be exerted by the C-18 methyl and side chain substituents. The opposite configurations were originally assigned to the adducts 127, but this was later corrected after X-ray analysis the correct assignments are shown in the diagram9. Monoepoxides, and in turn allylic alcohols, have been furthermore prepared from the adducts 1210. 

Figure 11 Biosynthesis of isoprenoid type cofactors. 18, Heme a 39, pyridoxal 5 -phosphate 43, 1-deoxy-D-xylulose 5-phosphate 46, thiamine pyrophosphate 83, acetyl-CoA 84, (S)-3-hydroxy-3-methylglutaryl-CoA 85, mevalonate 86, isopentenyl diphosphate (IPP) 87, dimethylallyl diphosphate (DMAPP) 88, pyruvate 89, D-glyceraldehyde 3-phosphate 90, 2C-methyl-D-erythritol 4-phosphate 91, 2C-methyl-erythritol 2,4-cyclodiphosphate 92, 1-hydroxy-2-methyl-2-( )-butenyl 4-diphosphate 93, polyprenyl diphosphate 94, cholecalciferol 95, fS-carotene 96, retinol 97, ubiquinone 98, menaquinone 99, a-tocopherol.

The role that vitamin D plays in the prevention of rickets and osteomalacia has been well documented. Studies have revealed the mechanism involved in the conversion of vitamin D into its metabolically active form responsible for the maintenance of calcium homeostasis. Cholecalciferol (vitamin D3) is first hydroxylated in the liver to 25-hydroxy-D3 this is then converted in the... 

Vitamers are chemically similar substances that have a qualitatively similar vitamin activity. Thus, vitamin D refers to ergocalciferol (Da) and cholecalciferol (D3) and sometimes to their 25-hydroxy- and 1,25-dihydroxy derivatives (Chapter 37). Similarly, pyridoxine (pyri-doxol), pyridoxal, and pyridoxamine are vitamin Be vitamers, riboflavin is the active form of vitamin Ba and cobalamin is vitamin Bia- The members of a particular vitamin family are functionally interchangeable and protect against deficiency symptoms for that vitamin. A vitamin and its corresponding deficiency disease are related as follows ... 

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... 

V.D2 (ergocalciferol) is derived from ergosterol, while V.D3 (cholecalciferol) is derived from 7-dehy-drocholesterol, both conversions occurring in the skin by the action of sunlight. V.D3 is converted enzymatically in the liver and kidneys to 25-hydroxy-... 

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