D Metabolism and Function

Activation of vitamin D3 by hydroxy lation. Vitamin D2 is metabolized to 1,25-(OH 2D2 (la,25-dihydroxyergocalciferol), its active form, by the same enzymes. 

In the liver, vitamin D is hydroxylated to 25-hydroxy vitamin D [25-(0H)2D], the principal circulating metabolite of vitamin D. In the kidney, hydroxylation at position 1 yields l,25-(OH)2D. This metabolite has the highest specific activity of the naturally occurring metabolites. 24,25-(0H)2D is also synthesized by renal mitochondria and in other tissues in relatively large amounts in animals with adequate intake of vitamin D, calcium, and 

25-(OH)D-la-hydroxylase is found in the inner mitochondrial membrane of the cells lining the proximal convoluted renal tubules. It is a mixed-function oxidase that requires molecular oxygen, a flavoprotein, a ferredoxin, and a cytochrome P-450 for activity. It is inhibited by carbon monoxide. Placental tissue contains la-hydroxylase activity, as do cultured bone cells and macrophages. This finding is of questionable importance under most circumstances, however, since l,25-(OH)2D is not present in significant amounts in nonpregnant, nephrectomized animals. 

An exception seems to be the hypercalcemia that occurs in some patients with chronic granulomatous diseases, such as tuberculosis, sarcoidosis, and silicosis. The observed increase in circulating l,25-(OH)2D is presumably due to the increased 25-(OH)D-la -hydroxylase activity found in the inflammatory cells in the granulomas. The hydroxylase activity does not appear to be under the usual tight feedback control by serum calcium levels. 

Renal osteodystrophy [due to decreased synthesis of 1,25-(0H)2D secondary to kidney failure] is treatable with synthetic l,25-(OH)2D or la-(OH)D. These compounds are also useful in other renal disorders such as hypoparathyroidism and vitamin D-dependent rickets. 

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H.F.DeLuca in "Vitamin D, Metabolism and Function", Monographs of Endocrinology, Springer-Werlag, Berlin, Heidelberg, New York, (1979). 

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H. F. De Luca, Vitamin D. Metabolism and Function, Springer-Verlag, Berlin, 1979. 

Acute-Duration Exposure. There are few data available for acute exposures in humans. This may be a function of the time required for the expression of effects (decreased heme synthesis, neurobehavioral changes, increased blood pressure, and interference with vitamin D metabolism) and the usual modes of exposure in humans, which are repeated ingestion of lead-containing dirt or lead-based paint chips in... 

D. V. Lynch and T. M. Dunn, An introduction to plant sphingolipids and a review of recent advances in understanding their metabolism and function, New Phytol., 161 (2004) 677-702. 

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Shelp, J., Bown, A.W. and McLean, M.D. (1999) Metabolism and function of gamma-aminobutyric acid. Trends in Plant Scl, 4,446-52. 

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.)...

Holick ME, Adams JS. Vitamin D metabolism and biological function. In Avioli LV, Krane SM, eds. Metabohc bone disease, 2nd ed. Philadelphia WB Saunders, 1990 155-95. 

Paul, R. J. (1986). Smooth muscle energy metabolism cytosolic compartmentation of metabolism and function. In Advances in Physiological Research (McLennan, H., Ledsome, J. R., McIntosh, C. H. S. and Jones, D. R., eds.), pp. 295-304, Plenum Press, New York. 

FIGURE 4.1 The pathway for the formation of GABA in tea. (From Shelp, B. J., McLean, M. D., and Bown, A. W. 1999. Metabolism and functions of y-aminobutyric acid. Trends Plant Sci. 4 446-52. With permission.)... 

Robinson, T. Metabolism and function of alkaloids in plants. Science 184, 430-435 (1974) Seigler, D. S, Primary roles for secondary compounds. Biochem. Syst. Ecol. 5, 195-199 (1977) Waller, G. R., Nowacki, E. K. Alkaloid Biology and Metabolism in Plants. Plenum Press, New York 1978... 

Svoboda J A 1984 Insect steroids Metabolism and function. In Nes W D, Fuller G, Tsai L-S (eds) Isopentenoids in plants Biochemistry and function. Marcel Dekker New York, 367-400... 

Grisolia, S., Carreras, J., Diederich, D. and Carache, S. (1970) Binding of 2,3-diphosphogIycerate (DPG) to oxyhemoglobin levels and effect of DPG on oxygen affinity of normal and abnormal blood. In Red Cell Metabolism and Function (G. Brewer, ed.), p. 39, Plenum Press, New York. 

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